Is Raynaud’s Disease Genetic?

Catherine on April 15, 2025

Open palm hands showing signs of Raynaud’s disease with pale or bluish fingers

Disclaimer: This article is for informational purposes only and is not intended for diagnostic use. LifeDNA does not provide diagnostic reports on any traits discussed. Genetics is just one piece of the puzzle; please consult a healthcare professional for comprehensive guidance on any health condition.

Imagine this: it’s a chilly day, and as you step outside, your fingers suddenly turn white, then blue, and maybe even red, accompanied by a tingling or numb sensation. For most people, cold hands are just a passing discomfort, but for those with Raynaud’s disease, these episodes are a recurring and sometimes painful reality. 

While the condition has been recognized for over a century, scientists are now digging deeper into its roots, particularly the role genetics plays in making some people more susceptible. So, what exactly is Raynaud’s, and how do our genes contribute to this curious condition? Let’s explore the science behind this condition in a way that’s clear and engaging, even if biology isn’t your daily cup of tea.

Raynaud’s disease, sometimes called Raynaud’s phenomenon, is a condition where blood vessels in the extremities, typically the fingers and toes, overreact to cold temperatures or stress. During an episode, these blood vessels clamp down more than they should, reducing blood flow and causing the affected areas to change color and feel cold or numb. For some, it’s a mild annoyance, but for others, it can lead to discomfort, pain, or even sores in severe cases.

Types of Raynaud’s Disease

There are two types of Raynaud’s: primary and secondary. Primary Raynaud’s is the more common form, often appearing in younger people, especially women, and isn’t usually linked to other health problems. Secondary Raynaud’s, on the other hand, is tied to other conditions, like autoimmune diseases ( lupus or rheumatoid arthritis) or injuries, and tends to be more serious. While cold and stress are well-known triggers, researchers have long suspected that genetics might explain why some people develop Raynaud’s while others don’t.

Genetics

Twin studies have indicated a significant genetic component in Raynaud’s. A 2007 study estimates the heritability of Raynaud’s to be around 55% based on 700 monozygotic and 726 dizygotic twins.

Studies have shown that genes influencing how blood vessels contract and relax are obvious candidates. Some variants in genes like ADRA2A and EDN1, which help regulate blood flow, might make the blood vessels more likely to constrict in response to cold. 

A large meta-analysis published in 2024 found eight genes linked to extreme constriction of blood vessels in response to the cold. This includes genes affecting blood vessel movement, the lining of blood vessels, and the immune system. Two genes, ADRA2A and NOS3, were shown to directly affect how strongly blood vessels respond to cold. 

ADRA2A gene provides instructions for making a protein called the alpha-2A adrenergic receptor. This receptor sits on the surface of certain nerve and muscle cells and plays a key role in how the nervous system controls blood vessel tone, especially in response to stress or cold. Two large studies published in 2023 show the robust genetic foundation of Raynaud’s. First is a genome-wide association study (GWAS) which showed the role of a genetic variant at alpha 2A-adrenoreceptor encoded by ADRA2A (SNP rs7090046). Another large 2023 GWAS study on 11,605 individuals diagnosed with Raynaud’s (and more than 1 million controls) showed that overactive adrenergic signaling through ADRA2A is a key cause of Raynaud’s.

The NOS3 gene (Nitric Oxide Synthase 3) provides instructions for making an enzyme called endothelial nitric oxide synthase (eNOS). This enzyme is primarily found in the endothelial cells that line blood vessels, and its main job is to produce nitric oxide (NO) — a gas that acts as a natural vasodilator. In Raynaud’s, where blood vessels constrict too much in response to cold, a lack of nitric oxide can make things worse. If the eNOSis underactive or its function is disrupted, the body may produce less nitric oxide, leading to excessive vasoconstriction and poor blood flow to the fingers and toes.

Epigenetics

Beyond inherited DNA, scientists are exploring epigenetic changes. These are factors that influence gene activity without altering the DNA sequence. Things like chronic stress, infections, or even hormones might switch certain genes on or off, making someone more likely to develop Raynaud’s later in life. This may explain why symptoms often appear in young adulthood, and why women are more frequently affected (potentially due to hormonal influences).

Why is early diagnosis important?

Diagnosing Raynaud’s disease early is important because this can help prevent complications, identify underlying conditions, and improve quality of life. 

Here’s why early diagnosis matters: 

Primary Raynaud’s is usually harmless and manageable. Secondary Raynaud’s can be a sign of serious autoimmune diseases like scleroderma, lupus, or rheumatoid arthritis. Early diagnosis also helps doctors run the right tests and catch the condition in its early stage, when treatment is more effective. Knowing the type and severity of Raynaud’s early allows for:

  • Lifestyle changes (like avoiding cold or quitting smoking)
  • Medications to improve blood flow
  • Regular monitoring for signs of autoimmune conditions

References

Genetic Response to Lithium Orotate

Catherine on April 14, 2025

This image features a set of white lithium orotate supplement pills alongside a DNA model, emphasizing the connection between genetics and individual response to the compound.

Disclaimer: This article is for informational purposes only and is not intended for diagnostic use. LifeDNA does not provide diagnostic reports on any traits discussed. Genetics is just one piece of the puzzle; please consult a healthcare professional for comprehensive guidance on any health condition.

Lithium orotate is gaining attention as a natural supplement with potential benefits for mental health, mood stability, and neurological function. Unlike the pharmaceutical form of lithium used in higher doses to treat bipolar disorder, lithium orotate is a compound made by binding lithium to orotic acid, which is thought to improve its absorption and delivery into cells. But how does this supplement work in the body, and how might genetics influence its effects?

You might want to read: Bacopa Monnieri and Genetics: The Effect on Brain Health

What Is Lithium Orotate?

Lithium is a naturally occurring trace element found in the earth’s crust, water sources, and some food items. It has long been used in medicine, especially in the form of lithium carbonate, to manage severe mood disorders like bipolar disorder. Lithium orotate is a different form, it contains a lower dose of elemental lithium, typically around 1-5 milligrams per tablet, compared to the much higher doses used in prescription lithium medications.

The orotate salt is thought to cross cell membranes more easily, delivering lithium to where it is needed without requiring high doses. This has led to the supplement’s popularity among those seeking mood support without the side effects often associated with prescription lithium.

Benefits of Lithium Orotate

Lithium orotate is believed to offer several benefits, particularly in the areas of mental and emotional health. These include:

  • Mood stabilization: It may help reduce mood swings and promote emotional balance.
  • Neuroprotection: Research suggests lithium may protect brain cells and promote the growth of new neural connections.
  • Reduced anxiety and irritability: Low-dose lithium is thought to help calm the nervous system.
  • Cognitive support: Some early evidence points to improved memory and learning.

Although most studies on lithium’s neuroprotective effects involve higher prescription doses, lithium orotate may provide subtle support over time, especially when used in combination with a healthy lifestyle and other nutrients.

How Lithium Orotate Works in the Body

Lithium acts on several biological pathways in the brain. It modulates neurotransmitters like dopamine, serotonin, and glutamate, which influence mood, motivation, and stress response. It also inhibits a key enzyme known as glycogen synthase kinase-3 (GSK-3), which is involved in inflammation and neuronal signaling. By reducing GSK-3 activity, lithium can promote the survival of brain cells and enhance synaptic plasticity—our brain’s ability to adapt and form new connections.

Lithium also increases levels of brain-derived neurotrophic factor (BDNF), a protein essential for brain health, memory, and mood regulation. Higher BDNF levels are associated with better mental resilience and reduced risk of depression.

Genetic Response to Lithium Orotate

Not everyone responds to lithium in the same way, and our genetics plays a key role in this variability. Several genes influence how lithium is absorbed, transported, and used in the body. Lithium in higher doses is a medicine used to treat bipolar disorder, but it doesn’t work the same way for everyone. Scientists think that differences in our genes might explain why some people respond well to lithium and others do not.

Some studies have looked at the entire human genome to find regions that might be linked to how people respond to lithium. These studies found several regions on different chromosomes that might be important. For example, some research pointed to loci on chromosomes 20, 15, 14, and 8 as possibly involved. One recent study in 2020 focused on a Japanese family and found a gene called DOCK5 on chromosome 8 that might be related to lithium response.

But here’s the problem: different studies have found different regions. This indicates there probably isn’t just one gene that controls lithium response. Instead, many genes may each have a small role like with many other polygenic traits.

 Several studies have looked closely at certain genes that might affect lithium response. Three genes come up a lot: GSK3β, BDNF, and SLC6A4. Genetic variants in these genes seem to be linked to either good or poor response to lithium. But not all studies agree on the very loci For example: For the BDNF gene, a variant called Val66Met was connected to lithium response in some studies, but not in others. Same for the SLC6A4 gene.. For the GSK3β gene, several gene variants have been found to berelated to lithium response, but results vary. This means that while these genes are likely to be important, their effects can differ depending on other factors.

In any case, genetics do play a part in how well lithium works for someone with bipolar disorder. But it’s not as simple as one “lithium response gene.” Many genes likely work together, and other factorslike the environment may also affect the response. Understanding these genes and other factors better could help doctors personalize lithium treatment in the future.

Sources of Lithium Orotate

Lithium is naturally present in small amounts in some food items and water supplies, especially in mineral-rich areas. However, the lithium content in food is generally too low to have a therapeutic effect. Supplementation with lithium orotate provides a consistent, low dose that may support mental well-being.

Lithium orotate supplements are widely available in health stores and online, usually in tablet form containing 1 mg to 5 mg of elemental lithium. It’s important to read labels carefully, as the total weight of lithium orotate is not the same as the elemental lithium content.

Who Might Benefit from Lithium Orotate?

Lithium orotate may be particularly helpful for individuals experiencing:

  • Mild mood instability or irritability
  • Chronic stress or burnout
  • Low resilience to emotional challenges
  • Cognitive fog or mental fatigue
  • A family history of mood disorders

Some people also take it to support recovery from brain injury, although more research is needed in this area. Since the dose is much lower than prescription lithium, it may offer a gentler way to support brain health and emotional balance.

Precautions and Side Effects

While lithium orotate is considered safe for many people at low doses, it’s not suitable for everyone. Individuals with kidney disease, thyroid problems, or those taking medications that influence lithium levels should use caution and consult a healthcare provider before starting supplementation.

Even at low doses, some people may experience side effects, especially with long-term use or if sensitivity is high. These may include:

  • Nausea or digestive discomfort: Some people report feeling queasy or experiencing mild stomach upset after taking lithium orotate. This may be due to how the body processes lithium or how the supplement is absorbed.
  • Mild tremors: A fine, involuntary shaking in the hands or fingers can occasionally occur. This is more common with higher doses of lithium but has also been reported in sensitive individuals at lower doses.
  • Increased thirst or urination: Lithium can affect how the kidneys manage fluids. As a result, you might feel thirstier than usual or notice that you’re urinating more often. This is usually mild but should be monitored.
  • Brain fog or sluggishness: Some users report feeling mentally dull, tired, or slow in their thinking after taking lithium orotate. This cognitive fatigue may result from how lithium influences brain chemistry in certain individuals.

These effects are generally uncommon with the low lithium content found in lithium orotate, but it’s still important to monitor your response. If any of these symptoms persist or worsen, it’s best to pause use and consult with a healthcare provider. Routine lab tests are not typically required with lithium orotate, but those using it regularly may benefit from periodic kidney and thyroid checkups to ensure long-term safety.

Personalized Lithium Supplementation

As interest in personalized health grows, more people are turning to genetic testing to determine how their bodies respond to various supplements. Lithium orotate is a prime candidate for such an approach. 

Lithium orotate offers a promising, low-dose option for supporting mental health and brain function. While it doesn’t replace prescription treatment for serious psychiatric conditions, it may benefit those looking for natural ways to enhance emotional balance and cognitive well-being. Genetics play a key role in determining who benefits most, making personalized approaches the future of supplementation.

It is important to note to always consult a healthcare provider before starting any new supplement, especially one that affects brain chemistry. With the right guidance, lithium orotate could be a valuable tool in your journey to better brain health.

References

The Role of Genetic Variations in Mercury Detoxification

Catherine on April 12, 2025

Image dietary sources of mercury detoxification.

Disclaimer: This article is for informational purposes only and is not intended for diagnostic use. LifeDNA does not provide diagnostic reports on any traits discussed. Genetics is just one piece of the puzzle; please consult a healthcare professional for comprehensive guidance on any health condition.

Lithium orotate is gaining attention as a natural supplement with potential benefits for mental health, mood stability, and neurological function. Unlike the pharmaceutical form of lithium used in higher doses to treat bipolar disorder, lithium orotate is a compound made by binding lithium to orotic acid, which is thought to improve its absorption and delivery into cells. But how does this supplement work in the body, and how might genetics influence its effects?

You might want to read: Bacopa Monnieri and Genetics: The Effect on Brain Health

What Is Lithium Orotate?

Lithium is a naturally occurring trace element found in the earth’s crust, water sources, and some food items. It has long been used in medicine, especially in the form of lithium carbonate, to manage severe mood disorders like bipolar disorder. Lithium orotate is a different form, it contains a lower dose of elemental lithium, typically around 1-5 milligrams per tablet, compared to the much higher doses used in prescription lithium medications.

The orotate salt is thought to cross cell membranes more easily, delivering lithium to where it is needed without requiring high doses. This has led to the supplement’s popularity among those seeking mood support without the side effects often associated with prescription lithium.

Benefits of Lithium Orotate

Lithium orotate is believed to offer several benefits, particularly in the areas of mental and emotional health. These include:

  • Mood stabilization: It may help reduce mood swings and promote emotional balance.
  • Neuroprotection: Research suggests lithium may protect brain cells and promote the growth of new neural connections.
  • Reduced anxiety and irritability: Low-dose lithium is thought to help calm the nervous system.
  • Cognitive support: Some early evidence points to improved memory and learning.

Although most studies on lithium’s neuroprotective effects involve higher prescription doses, lithium orotate may provide subtle support over time, especially when used in combination with a healthy lifestyle and other nutrients.

How Lithium Orotate Works in the Body

Lithium acts on several biological pathways in the brain. It modulates neurotransmitters like dopamine, serotonin, and glutamate, which influence mood, motivation, and stress response. It also inhibits a key enzyme known as glycogen synthase kinase-3 (GSK-3), which is involved in inflammation and neuronal signaling. By reducing GSK-3 activity, lithium can promote the survival of brain cells and enhance synaptic plasticity—our brain’s ability to adapt and form new connections.

Lithium also increases levels of brain-derived neurotrophic factor (BDNF), a protein essential for brain health, memory, and mood regulation. Higher BDNF levels are associated with better mental resilience and reduced risk of depression.

Genetic Response to Lithium Orotate

Not everyone responds to lithium in the same way, and our genetics plays a key role in this variability. Several genes influence how lithium is absorbed, transported, and used in the body. Lithium in higher doses is a medicine used to treat bipolar disorder, but it doesn’t work the same way for everyone. Scientists think that differences in our genes might explain why some people respond well to lithium and others do not.

Some studies have looked at the entire human genome to find regions that might be linked to how people respond to lithium. These studies found several regions on different chromosomes that might be important. For example, some research pointed to loci on chromosomes 20, 15, 14, and 8 as possibly involved. One recent study in 2020 focused on a Japanese family and found a gene called DOCK5 on chromosome 8 that might be related to lithium response.

But here’s the problem: different studies have found different regions. This indicates there probably isn’t just one gene that controls lithium response. Instead, many genes may each have a small role like with many other polygenic traits.

 Several studies have looked closely at certain genes that might affect lithium response. Three genes come up a lot: GSK3β, BDNF, and SLC6A4. Genetic variants in these genes seem to be linked to either good or poor response to lithium. But not all studies agree on the very loci For example: For the BDNF gene, a variant called Val66Met was connected to lithium response in some studies, but not in others. Same for the SLC6A4 gene.. For the GSK3β gene, several gene variants have been found to berelated to lithium response, but results vary. This means that while these genes are likely to be important, their effects can differ depending on other factors.

In any case, genetics do play a part in how well lithium works for someone with bipolar disorder. But it’s not as simple as one “lithium response gene.” Many genes likely work together, and other factorslike the environment may also affect the response. Understanding these genes and other factors better could help doctors personalize lithium treatment in the future.

Sources of Lithium Orotate

Lithium is naturally present in small amounts in some food items and water supplies, especially in mineral-rich areas. However, the lithium content in food is generally too low to have a therapeutic effect. Supplementation with lithium orotate provides a consistent, low dose that may support mental well-being.

Lithium orotate supplements are widely available in health stores and online, usually in tablet form containing 1 mg to 5 mg of elemental lithium. It’s important to read labels carefully, as the total weight of lithium orotate is not the same as the elemental lithium content.

Who Might Benefit from Lithium Orotate?

Lithium orotate may be particularly helpful for individuals experiencing:

  • Mild mood instability or irritability
  • Chronic stress or burnout
  • Low resilience to emotional challenges
  • Cognitive fog or mental fatigue
  • A family history of mood disorders

Some people also take it to support recovery from brain injury, although more research is needed in this area. Since the dose is much lower than prescription lithium, it may offer a gentler way to support brain health and emotional balance.

Precautions and Side Effects

While lithium orotate is considered safe for many people at low doses, it’s not suitable for everyone. Individuals with kidney disease, thyroid problems, or those taking medications that influence lithium levels should use caution and consult a healthcare provider before starting supplementation.

Even at low doses, some people may experience side effects, especially with long-term use or if sensitivity is high. These may include:

  • Nausea or digestive discomfort: Some people report feeling queasy or experiencing mild stomach upset after taking lithium orotate. This may be due to how the body processes lithium or how the supplement is absorbed.
  • Mild tremors: A fine, involuntary shaking in the hands or fingers can occasionally occur. This is more common with higher doses of lithium but has also been reported in sensitive individuals at lower doses.
  • Increased thirst or urination: Lithium can affect how the kidneys manage fluids. As a result, you might feel thirstier than usual or notice that you’re urinating more often. This is usually mild but should be monitored.
  • Brain fog or sluggishness: Some users report feeling mentally dull, tired, or slow in their thinking after taking lithium orotate. This cognitive fatigue may result from how lithium influences brain chemistry in certain individuals.

These effects are generally uncommon with the low lithium content found in lithium orotate, but it’s still important to monitor your response. If any of these symptoms persist or worsen, it’s best to pause use and consult with a healthcare provider. Routine lab tests are not typically required with lithium orotate, but those using it regularly may benefit from periodic kidney and thyroid checkups to ensure long-term safety.

Personalized Lithium Supplementation

As interest in personalized health grows, more people are turning to genetic testing to determine how their bodies respond to various supplements. Lithium orotate is a prime candidate for such an approach. 

Lithium orotate offers a promising, low-dose option for supporting mental health and brain function. While it doesn’t replace prescription treatment for serious psychiatric conditions, it may benefit those looking for natural ways to enhance emotional balance and cognitive well-being. Genetics play a key role in determining who benefits most, making personalized approaches the future of supplementation.

It is important to note to always consult a healthcare provider before starting any new supplement, especially one that affects brain chemistry. With the right guidance, lithium orotate could be a valuable tool in your journey to better brain health.

References

The Impact of Pthalates on Your Genes

Catherine on April 11, 2025

Woman spraying perfume on her wrist, representing exposure to phthalates that may affect gene expression

Disclaimer: This article is for informational purposes only and is not intended for diagnostic use. LifeDNA does not provide diagnostic reports on any traits discussed. Genetics is just one piece of the puzzle; please consult a healthcare professional for comprehensive guidance on any health condition.

Phthalates are everywhere. These chemicals, often added to plastics to make them more flexible and durable, can be found in a wide variety of household products. From food packaging and cosmetics to medical devices and children’s toys, phthalates are ingrained in our everyday lives. However, despite their convenience, phthalates may pose potential risks to human health. 

What Are Phthalates?

Phthalates are a group of chemicals primarily used as plasticizers, meaning they make plastic more flexible and durable. These chemicals can be found in everyday products like vinyl flooring, shower curtains, food packaging, perfumes, and even medical devices. They are also used in personal care products such as shampoos, deodorants, and nail polishes.

But what makes phthalates particularly concerning isn’t just their widespread presence. It’s the way they interact with our bodies. Phthalates are considered endocrine disruptors, meaning they interfere with the body’s hormonal systems. This disruption may lead to a variety of health problems, including developmental disorders, fertility issues, and metabolic conditions like obesity and diabetes.

But phthalates’ potential impact doesn’t stop there. They may also influence our genes and how they function, leading to genetic and epigenetic changes that can persist over time.

The Genetics Behind Phthalate Exposure

Phthalates interact with our DNA, potentially altering gene expression. Gene expression refers to the process in which our DNA is used to make proteins, which are crucial for nearly every function in our body. The way our genes are expressed may be influenced by environmental factors like chemicals, and phthalates are important in this process.

The changes phthalates cause don’t always involve changes to the DNA sequence itself. Instead, phthalates can affect how genes are turned on or off. Phthalates can change how our body reads and uses its genetic instructions, and these so called epigenetic changes can have far-reaching consequences.

DNA Methylation

One of the main ways phthalates influence gene expression is through a process called DNA methylation. DNA methylation involves adding a small chemical group (a methyl group) to the DNA molecule. This small change can silence or activate certain genes, essentially turning them on or off.

Recent studies have shown that exposure to phthalates, especially during critical periods of development like pregnancy, can alter DNA methylation patterns. This can lead to genes being turned off or on at inappropriate times, which may contribute to developmental disorders, immune dysfunction, and even cancer.

For example, a study on phthalate exposure during pregnancy found that it caused changes in the methylation of genes related to lung development. These changes were linked to a higher risk of asthma in children born to mothers who had been exposed to phthalates during pregnancy. This is just one example of how small changes in gene expression can have significant consequences for long-term health.

Histones

In addition to DNA methylation, phthalates can also alter histones, proteins that help organize and package DNA in cells. Histones control how tightly DNA is wound, which affects how easily genes can be accessed for reading and transcription. By modifying histones, phthalates can make certain genes more or less accessible, leading to changes in gene expression.

One interesting aspect of phthalate-induced changes in histones is their potential to influence immune function. Phthalates have been shown to affect histone modifications in genes that regulate immune responses, which could make individuals more susceptible to infections or autoimmune diseases. This is another example of how phthalates, by modifying gene expression, can have cascading effects on health.

MicroRNAs

MicroRNAs (miRNAs) are tiny molecules that play a crucial role in regulating gene expression and are important epigenetic regulators in addition to the DNA methylation and histone modifications. These small RNA molecules help determine which genes are expressed and when, acting as messengers that control gene activity. Phthalates have been shown to interfere with the production and activity of miRNAs, which can disrupt normal gene regulation.

Research has found that exposure to phthalates during early development can alter the levels of specific miRNAs in the body. These changes can affect the development of organs like the brain and lungs, and may contribute to diseases like cancer, cardiovascular conditions, and even developmental disorders. The ability of phthalates to impact miRNAs highlights their far-reaching influence on genetic regulation.

Phthalates and the Health of Future Generations

One of the most fascinating but worrisome aspects of phthalate exposure is that the effects don’t just end with the person exposed. The genetic and epigenetic changes caused by phthalates can be passed down to future generations, creating a multigenerational health impact.

For example, one study explored how phthalate exposure in fathers could affect the genetic material passed on to their children. It turns out that exposure to phthalates can alter the germline DNA in sperm, potentially affecting the health of the offspring. This is particularly concerning because the genetic changes may not only affect the individual who was exposed but could also be passed down to their children and even their grandchildren.

Even when the germline DNA sequence may not be affected by phthalates the  changes caused by phthalates may be inherited epigenetically. These mechanisms affect , the way genes are expressed (or not expressed) in different types of cells in the body and these changes can be passed down. This adds another layer of complexity to the long-term health effects of phthalates, as the consequences can ripple through generations.

How Phthalates Impact Specific Health Conditions

Phthalates have been linked to a variety of health conditions, many of which involve genetic and epigenetic changes. Below, we’ll take a closer look at some of the key areas where phthalates have been found to play a significant role.

Reproductive Health

Phthalates are notorious for their impact on reproductive health. These chemicals can disrupt hormone levels, affecting both male and female fertility. In men, phthalates can alter the DNA in sperm, which may contribute to infertility or other reproductive issues. In women, phthalates have been linked to altered hormone regulation, which could lead to complications like early menopause or difficulty conceiving.

Interestingly, the effects of phthalates on reproductive health can extend beyond the individual who was exposed. Studies have shown that phthalate exposure in one generation can influence fertility and reproductive health in the next generation, either through genetic changes or epigenetic alterations.

Metabolic Diseases

Phthalate exposure has also been linked to metabolic diseases like obesity and diabetes. These conditions are influenced by a combination of genetic factors and environmental exposures, and phthalates appear to play a role in disrupting metabolic regulation. Changes in gene expression caused by phthalates can alter the way the body processes fat, glucose, and other essential nutrients, leading to an increased risk of metabolic disorders.

Cancer Risk

One of the most concerning implications of phthalate exposure is its potential link to cancer. Some studies have shown that phthalates can interfere with the normal function of genes that control cell growth, potentially leading to cancer. These chemicals can affect both DNA repair mechanisms and the regulation of genes that are involved in controlling the cell cycle, which could increase the likelihood of cancerous cell growth.

Research has specifically linked phthalates to cancers such as breast cancer and liver cancer. By altering gene expression and interfering with normal cellular functions, phthalates may contribute to the development of these diseases. The relationship between phthalates and cancer remains an area of active research, but early findings suggest a concerning connection.

Neurodevelopmental Disorders

Another area where phthalates have a significant impact is neurodevelopment. Phthalates, especially when exposure occurs during pregnancy or early childhood, have been linked to developmental disorders such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). These conditions are influenced by a complex interplay of genetic and environmental factors, and phthalates appear to exacerbate genetic susceptibility to these disorders.

Phthalates can affect the development of the brain by altering gene expression in neural cells, which may affect brain structure and function. Studies have found that phthalates can influence the development of neurotransmitter systems, which are critical for proper brain function. This may contribute to behavioral issues and learning difficulties later in life.

References:

Understanding the Heritability of Teeth Cavities

Catherine on April 10, 2025

Close-up of teeth cavities, representing the genetic link to tooth decay.

Disclaimer: This article is for informational purposes only and is not intended for diagnostic use. LifeDNA does not provide diagnostic reports on any traits discussed. Genetics is just one piece of the puzzle; please consult a healthcare professional for comprehensive guidance on any health condition.

Overview

We’ve all heard it before, “Brush your teeth or you’ll get cavities!” While oral hygiene, diet, and dentist visits undeniably plays an important role in dental health, an important question remains, can your genes be partly to blame for your cavities?

Understanding both genetic and non-genetic factors is essential because it gives us a more complete picture of what truly affects dental health. This may help individuals make informed choices, have specific preventive care more effectively, and even lead to personalized dental treatments in the future.

What Are Cavities?

Dental cavities, or caries, are permanent damage to the tooth’s surface caused by bacteria that feed on sugars and release acids. These acids erode tooth enamel and can lead to painful infections if untreated. While brushing, flossing, and reducing sugar intake are key preventive strategies, not everyone with good oral hygiene avoids cavities and not everyone with poor habits gets them.

Genes That Shape Your Teeth

Several specific genes influence tooth development, enamel formation, and salivary composition each of which can affect your risk for cavities.

Multiple studies  have revealed that mutations in genes like ENAM (enamelin) and AMELX (amelogenin) are linked to enamel defects that make teeth more vulnerable to decay. Other enamel matrix genes also play a role in determining the thickness and mineralization of enamel. Even minor differences in enamel quality due to genetic variation can significantly influence decay risk.

Genes influencing saliva composition can also influence cavity risk. Saliva does more than just help you chew, it neutralizes acids, remineralizes teeth, and carries protective proteins. 

Variants in genes such as MUC7, which influence salivary mucin production, may alter its antimicrobial and buffering properties. Studies  conclude that people with specific variants may have reduced protection from acids and harmful bacteria, increasing their risk of developing cavities.

Saliva-related gene expression also appears to differ in individuals with high versus low caries risk, suggesting that personalized saliva profiles—shaped by genetics—might one day be used to predict or prevent cavities.

One of the strongest types of evidence pointing to a genetic link in cavities comes from studies on twins. Identical twins share 100% of their genes, while fraternal twins share about 50%. Comparing dental health between these groups helps researchers understand the role of heredity.

Multiple twin studies have found that genetic factors contribute significantly to an individual’s risk of developing dental caries. Heritability estimates have ranged from 20% to 65%, indicating that a substantial portion of cavity risk could be inherited. The higher similarity in decay rates among identical twins compared to fraternal twins strongly supports the role of genetics.

Immune System Genes and the Battle Against Bacteria

Tooth decay is caused by bacteria—but not everyone’s immune system responds to these invaders in the same way. Some people may be genetically better equipped to fight off harmful microbes in their mouths.

Genetic variation in immune response genes, such as those encoding cytokines and toll-like receptors, can influence caries susceptibility. Polymorphisms in genes like IL1B and TLR2 may lead to stronger or weaker inflammatory responses. Research says that Inadequate immune responses may allow decay-causing bacteria to flourish, while overly aggressive responses could damage oral tissues.

The Role of the Oral Microbiome

Each of us hosts a unique mix of bacteria in our mouths, known as the oral microbiome. While shaped by environment and diet, genetics may also play a role in determining which microbial communities dominate.

Evidence shows that the host genome can influence the composition of the oral microbiome, meaning your genes may indirectly affect your cavity risk by altering the oral environment to be more or less favorable for harmful bacteria.

For example, genetic differences that affect saliva’s mineral content could lead to microbial imbalances that raise your risk of decay.

Can Genetic Testing Predict Cavities?

While multiple studies have proposed integrating genetic risk factors into dental care, current findings may not be strong enough to support widespread predictive testing.

Many of the identified genetic variants have only small effects on their own. Tooth decay likely results from a complex interaction of many genes, each contributing a small part, along with lifestyle and environmental factors as suggested by some recent genome-wide association studies (GWAS).

Nosingle “cavity gene” has been found. Still, as more genetic data is gathered, future breakthroughs may make genetic testing a practical part of oral care planning.

Personalized Oral Health

Gene expression profiles in saliva may serve as non-invasive biomarkers to predict caries risk and allow for proactive, individualized care.

Another key takeaway is the role of education and awareness in applying genetic insights. If people understand that they may be genetically predisposed to cavities, they might be more motivated to take preventive actions.

For parents, this could mean early interventions for children at risk, such as dental sealants or frequent fluoride varnish treatments. It also reduces blame or stigma around dental issues that may not be fully preventable, even with good hygiene.

References:

 

Understanding Inclusion Body Myositis

Catherine on April 7, 2025

Woman holding her arm due to muscle weakness, representing Inclusion Body Myositis

Disclaimer: This article is for informational purposes only and is not intended for diagnostic use. LifeDNA does not provide diagnostic reports on any traits discussed. Genetics is just one piece of the puzzle; please consult a healthcare professional for comprehensive guidance on any health condition.

Overview

Inclusion Body Myositis (IBM) is a rare and progressive muscle disorder that primarily affects adults over the age of 50. It causes slow but steady muscle weakness, especially in the arms and legs. While IBM is often mistaken for other types of inflammatory muscle disease, it stands apart due to its unique cellular changes and resistance to most conventional treatments.

While the exact cause of Inclusion Body Myositis remains unknown, researchers have identified several contributing factors that appear to play a role in its development. These include autoimmune activity, abnormal protein buildup, and age-related cellular changes.

You might want to read: The Genetics of Age-related Muscle Mass Loss

Causes of Inclusion Body Myositis

The exact triggers of IBM are not fully understood, but researchers believe it develops due to a combination of immune system issues and underlying cellular defects. Key contributing factors include:

  • Autoimmune response
     IBM is classified as an inflammatory myopathy, which means the body’s immune system mistakenly attacks its own muscle tissue. This autoimmune reaction leads to chronic inflammation and progressive damage to muscle fibers.

  • Protein misfolding and accumulation
     A hallmark of IBM is the buildup of abnormal clumps (inclusion bodies) inside muscle cells. These clumps are made of misfolded proteins that the body fails to clear. The presence of these inclusions is what gives IBM its name and contributes to muscle degeneration.

  • Genetic susceptibility
     While IBM is not typically inherited in a straightforward way, certain genetic aspects(like variations in the HLA-DRB1 gene) may increase the risk. These genetic variants may influence immune function or how cells process and remove damaged proteins.

  • Age-related changes
     IBM mostly affects people over 50, suggesting that aging muscles may be more vulnerable to the underlying disease processes. As we age, the body becomes less efficient at managing inflammation and repairing damaged tissue.

Symptoms of Inclusion Body Myositis

IBM usually progresses slowly over several years, with symptoms that can vary from person to person. Common signs include:

  • Weakness in the thighs and forearms
    IBM tends to affect specific muscle groups, particularly the quadriceps (front thigh muscles) and finger flexors (muscles used to grip). This leads to difficulty rising from chairs or holding objects.

  • Frequent falls and unsteady walking
    Leg weakness often causes people with IBM to lose balance or trip easily. Falls become more common as the condition progresses.

  • Difficulty swallowing
    Involvement of the throat muscles can make swallowing difficult, increasing the risk of choking or aspiration pneumonia.

  • Wasting or shrinkage of muscles
    As muscle tissue deteriorates, visible muscle wasting (atrophy) may occur, especially in the forearms and thighs.

  • Slow but steady progression
    IBM develops gradually over time and may take years before becoming significantly disabling. Unlike other forms of myositis, it typically does not respond to steroids or immunosuppressants.

Genetics on IBM 

 Research  studies have looked at immune-related genes and found that certain variations in the HLA-DRB1 gene may increase the risk of IBM. These variations affect specific amino acid coding positions in the gene, possibly changing its function, which could help explain why some people are more likely to develop the disease. Another gene, CCR5, has also shown a possible link to IBM, suggesting there may be shared genetic features between IBM and other autoimmune diseases. In addition, rare genetic changes have been discovered in genes like VCP, SQSTM1, and FYCO1, which are involved in how the body breaks down damaged proteins. Studies also found large mitochondrial DNA deletions in certain muscle cells, suggesting that mitochondrial damage could be part of IBM as well. Similar findings have been reported by a more recent study on mitochondrial DNA variants in IBM. Altogether, these findings support the idea that IBM is caused by a combination of immune system problems, protein breakdown issues, and mitochondrial dysfunction. Scientists now believe that inflammation in the muscles may come first, leading to a buildup of damaged proteins and mitochondrial changes. Different research approaches have helped uncover these clues, and ongoing global studies are collecting more samples to improve future research. Larger studies that include diverse populations, along with advanced genetic testing methods like whole-exome and whole-genome sequencing, are expected to reveal even more about how genetics contributes to IBM.

How to Care for Someone with Inclusion Body Myositis

While there is no known cure for Inclusion Body Myositis (IBM), supportive care can make a significant difference in a patient’s quality of life. Physical therapy plays an important role in helping maintain mobility and muscle strength through gentle, customized exercises that avoid overexertion. Occupational therapy is also valuable, offering practical tools and adaptations to support daily tasks as fine motor skills decline. As leg weakness progresses, mobility aids such as canes, walkers, or wheelchairs may become necessary to prevent falls and maintain independence.

For those experiencing swallowing difficulties, working with a nutritionist or speech therapist can help modify diets to ensure safe and adequate nutrition. Emotional support is equally crucial—living with a chronic, progressive condition can be isolating, so having access to support groups, therapy, and a strong social network can help ease the psychological burden. Regular visits to a neurologist are essential to monitor progression and manage emerging symptoms. In some cases, patients may also qualify for clinical trials exploring potential new treatments. A coordinated, multidisciplinary approach remains the best strategy for managing IBM over time.

Can You Get Tested for Inclusion Body Myositis?

Diagnosing IBM can be challenging because its symptoms often resemble other muscle diseases like polymyositis or ALS. However, there are several ways to confirm it:

  • Blood tests
    These may show elevated muscle enzymes like creatine kinase (CK), but levels are usually only mildly increased in IBM.

  • Electromyography (EMG)
    This test measures electrical activity in muscles and helps identify patterns consistent with IBM-related muscle damage.

  • Muscle biopsy
    A definitive diagnosis usually requires a biopsy, where a small sample of muscle tissue is analyzed under a microscope. Inclusion bodies and other cellular changes are key markers of IBM.

  • Genetic and immune testing
    While there is no standard genetic test for IBM, some individuals may benefit from genetic screening to identify genetic variants like those in HLA-DRB1. Research is ongoing into the genetic underpinnings of IBM, and new insights may shape future diagnostics.

If you’re experiencing unexpected muscle weakness or other concerning symptoms, speak with a healthcare provider. A neurologist or rheumatologist familiar with neuromuscular disorders is best equipped to assess and guide you through the appropriate tests.

References

Genetics of Pernicious Anemia

Catherine on April 6, 2025

This image shows a man holding his stomach in visible discomfort, symbolizing one of the common symptoms of pernicious anemia.

Disclaimer: This article is for informational purposes only and is not intended for diagnostic use. LifeDNA does not provide diagnostic reports on any traits discussed. Genetics is just one piece of the puzzle; please consult a healthcare professional for comprehensive guidance on any health condition.

Overview

Pernicious anemia may sneak up on someone without them realizing that they actually have a serious condition. At first, they might just feel tired or experience brain fog, symptoms easy to brush off as everyday stress or busy life. But underneath, their body isn’t absorbing enough vitamin B12 because of an immune system issue. Genetics may also play a role, making some people more likely to develop this condition. Knowing about these hidden connections can help them get diagnosed and treated sooner.

Recent statistics shows that Pernicious anemia typically affects people between the ages of 60 and 80, especially those of Northern European descent. In the United States, it is estimated to affect about 151 in every 100,000 people. Although it is more common in this group, anyone may develop the condition.

Understanding this condition is important because the early symptoms are often subtle and easy to miss. If this is left untreated, it may lead to serious complications, including nerve damage and cognitive issues. Being aware of the symptoms and risk factors may help people seek timely medical advice and improve their quality of life.

What Is Pernicious Anemia?

Pernicious anemia is a type of megaloblastic anemia,  a type of anemia where the body produces unusually large and immature red blood cells that don’t work properly. This happens because the body lacks important nutrients, usually vitamin B12 or folate (vitamin B9) that are needed to make healthy red blood cells. As a result, the blood can’t carry enough oxygen to the body’s tissues, causing symptoms like tiredness and weakness.

The root cause is typically an autoimmune response that attacks the stomach’s parietal cells or intrinsic factor, a protein necessary for vitamin B12 absorption. Without adequate vitamin B12, the body can’t produce healthy red blood cells, leading to symptoms like fatigue, weakness, numbness, and cognitive difficulties.

You may want to read: How Genetics May Affect Vitamin B12 Levels 

What Are the Symptoms of Pernicious Anemia?

Pernicious anemia symptoms often develop slowly and may be mistaken for other conditions, especially in the early stages. Because vitamin B12 is involved in red blood cell formation and neurological health, symptoms can affect many systems in the body.

Common Symptoms Include:

  • Fatigue and Weakness:
    As red blood cell production declines, less oxygen circulates through the body, leading to persistent tiredness and a feeling of weakness even after rest.
  • Pale or Yellowish Skin:
    The lack of healthy red blood cells may cause the skin to look pale, while the breakdown of defective red cells can give the skin a slightly yellow tone.
  • Shortness of Breath and Dizziness:
    Low red blood cell count reduces oxygen delivery, making people feel out of breath during activities or even at rest.
  • Numbness and Tingling in Hands and Feet:
     deficiency in vitamin B12 can lead to peripheral nerve damage, causing sensations like pins and needles—especially in the extremities.
  • Balance and Coordination Problems:
    Nerve damage can also impact motor control, resulting in difficulty walking, poor coordination, or frequent falls.
  • Cognitive Issues:
    Many people with untreated pernicious anemia experience brain fog, memory loss, and even mood changes like irritability or depression.
  • Glossitis and Mouth Ulcers:
    Inflammation of the tongue (glossitis) can cause pain, redness, and a smooth appearance. Mouth sores are also common.
  • Digestive Symptoms:
    Some may experience nausea, bloating, or appetite loss, especially if the autoimmune response affects stomach lining function.
  • Fast Heart Rate or Irregular Heartbeats:
    In response to low oxygen levels, the heart may beat faster to compensate, potentially leading to palpitations or arrhythmia.

Causes of Pernicious Anemia

Primary Causes:

The main cause of pernicious anemia is when the body’s immune system makes a mistake and attacks components in the stomach that help absorb vitamin B12. Normally, special cells in the stomach called parietal cells make a protein called intrinsic factor. This protein is needed to help the body take in vitamin B12 from food.

In people with pernicious anemia, the immune system creates antibodies that destroy these parietal cells. Sometimes, the antibodies attack the intrinsic factor protein itself, stopping it from working properly. Because of this, the body can’t absorb enough vitamin B12, which is important for making healthy red blood cells. Also, long-term swelling and damage in the stomach lining, called autoimmune gastritis, often happens along with pernicious anemia and makes the problem worse.

Other Contributing Factors:
Aside from problems with the immune system, other things may raise your chances of getting pernicious anemia. Your genes play a big part, but some people are born with genetic variation that makes their immune system more likely to attack the lining of the stomach. If you have family members with autoimmune diseases like type 1 diabetes or thyroid problems, your risk may be higher too. Age matters as well, and people over 60 get this condition more often. 


Genetic Studies on Pernicious Anemia

Researchhas shown that pernicious anemia is closely linked to genetics and the immune system. Researchers analyzed the DNA of over 2,000 people with pernicious anemia and compared it to more than 650,000 people without the condition. They discovered several genetic markers that are much more common in those affected.

Three large European biobanks were used: the Estonian Biobank (EstBB), UK Biobank (UKBB), and FinnGen. In Estonia, 378 cases and over 138,000 controls were identified, with a disease rate of 0.3%. In the UK, 754 cases and 390,000 controls were found, with a rate of 0.2%. In Finland, researchers looked at a broader category called “Vitamin B12 deficiency anemia,” identifying 1,034 cases and 131,000 controls, with a rate of 0.8%. All studies applied a special analysis method that adjusted for factors such as age, sex, and genetics. The combined results from these populations were analyzed together in a meta-analysis to better identify genetic links to the disease.

The meta-analysis pinpointed five specific genetic variants strongly associated with pernicious anemia. These variants are located on Chromosome 1 (rs6679677), Chromosome 2 (rs12616502) , Chromosome 6 (rs28414666), Chromosome 10 (rs2476491) , and Chromosome 21 (rs74203920). Importantly, these findings were consistent across all three biobanks, confirming the genetic basis of this autoimmune form of vitamin B12 deficiency. The genetic markers are near genes involved in immune system function and other autoimmune conditions, suggesting that inherited immunological traits may increase the risk of developing pernicious anemia. Overall, this research confirms that genetics plays a significant role in pernicious anemia..

Management and Treatment

The primary approach to managing pernicious anemia involves restoring and maintaining adequate levels of vitamin B12, typically through intramuscular injections since the body cannot absorb the vitamin naturally due to the lack of intrinsic factor. Once B12 levels stabilize, some patients may switch to high-dose oral supplements under medical supervision. Treatment is ongoing and often lifelong, as the underlying absorption issue remains. In certain cases, antibiotics may be prescribed if intestinal bacteria are interfering with B12 absorption. Many individuals begin to feel better within days of starting treatment, although it may take several weeks for noticeable improvements. Long-term management generally requires regular monitoring and continuous supplementation to prevent recurrence and complications.

LifeDNA and Vitamin B12 

LifeDNA offers a personalized Vitamins and Supplements Report based on your DNA to help you understand your body’s unique nutritional needs. This  includes insights on Vitamin B and D levels, giving you a clearer picture of what your body may need.

Vitamin B12 is one of the essential nutrients covered in these reports. Since the body doesn’t produce B12 naturally, it must come from food or supplements. Good sources include eggs, red meat, soy, nuts, seeds, shellfish, leafy greens, mushrooms, and bananas. While the recommended daily amount for adults is 2.4 mcg, higher amounts—up to 1000 mcg—may be needed for those with a deficiency. Fortunately, excess B12 is typically excreted through urine, making it safe to take more than the minimum.


References

Genetics and Response to Metformin

Catherine on April 5, 2025

Metformin pills on a surface, representing how genetics can influence drug effectiveness and side effects

Disclaimer: This article is for informational purposes only and is not intended for diagnostic use. LifeDNA does not provide diagnostic reports on any traits discussed. Genetics is just one piece of the puzzle; please consult a healthcare professional for comprehensive guidance on any health condition.

Overview

Metformin is one of the most commonly prescribed medications for type 2 diabetes. It helps control blood sugar, is generally well-tolerated, and it is studied for its potential benefits as an anti-aging and cancer prevention agent. But here’s a little catch you need to know; not everyone responds to metformin the same way.

While metformin works well for some people, others may get more side effects or see little improvement. The answer lies in our genes. In recent years, researchers have begun uncovering how genetic differences affect our response to this medication. If you’re planning on taking Metformin, understanding how your DNA may influence its effectiveness to personalize your treatment plan and improve outcomes is important.

You may want to read: Are You Always Craving Sugary Drinks? Your Genetics May Be the Cause

What Is Metformin?

Metformin is a medication commonly used to help people with type 2 diabetes manage their blood sugar levels. It is often the first treatment doctors recommend because it works well and doesn’t usually cause weight gain or dangerously low blood sugar levels like some other diabetes medicines.

Metformin is approved by the FDA and is most effective when combined with healthy habits like eating well and exercising regularly. By keeping blood sugar levels in a healthy range, metformin can help prevent serious long-term problems such as kidney damage, nerve pain, vision loss, foot or leg amputations, and even heart attacks or strokes.

In addition to diabetes, metformin is also being studied for other health conditions, including polycystic ovary syndrome (PCOS), obesity, and aging.

How Does Metformin Work?

Metformin helps lower blood sugar in three important ways:

  • It reduces how much sugar the liver makes: The liver naturally produces glucose, but metformin slows this process down so less sugar enters the bloodstream.
  • It helps the body respond better to insulin: Insulin is the hormone that helps move sugar from the blood into the cells. Metformin makes the body more sensitive to insulin, so sugar is used more efficiently.

  • It lowers the amount of sugar absorbed from food: After eating, some sugar from food gets absorbed into the blood through the intestines. Metformin helps reduce this absorption, which keeps blood sugar from rising too high.

Why People Respond Differently to Metformin

While metformin works well for many, about 1 in 3 people either don’t get optimal results or experience side effects like nausea, diarrhea, or abdominal pain. For some, this leads to stopping the medication altogether. One major factor is our  genetic variation. Your DNA may influence how your body absorbs metformin or your liver and kidneys process it and how sensitive your cells are to insulin.

A seminal genome-wide association study (GWAS) discovered  that genetic differences help explain why people respond differently to metformin, the most widely used drug for type 2 diabetes (T2D). Researchers studied over 13,000 individuals from diverse ethnic backgrounds and discovered that a variant in the SLC2A2 gene, which affects the glucose transporter GLUT2, is linked to a significantly stronger response to metformin. People with this variant have reduced GLUT2 activity, limiting glucose processing in the liver—an effect that metformin helps reverse. The variant was also associated with higher body weight, potentially explaining why metformin often works best in overweight patients. These findings support a move toward precision medicine in diabetes care, suggesting that some patients may benefit from higher doses or earlier intervention based on their genetic profile.

Several recent pharmacogenetic studies have demonstrated that variations in genes  encoding various cellular transporters are associated with metformin pharmacokinetics, pharmacodynamics and metformin response.

Known  Factors Affecting Metformin Response

While genetics provide valuable insight, they represent only one aspect of the overall picture. Several other factors can significantly influence an individual’s response to metformin. However, these factors may also be affected by your genetic make-up.:

  • Diet and Exercise Habits – What you eat and how active you are can impact blood sugar control and insulin sensitivity, which can affect metformin’s effectiveness.
  • Other Medications – Some drugs may interact with metformin, either enhancing or reducing its effects.
  • Liver or Kidney Function – Since metformin is processed by the liver and excreted by the kidneys, impaired function in these organs can alter how the drug works.
  • Gut Health and Microbiome – A healthy balance of gut bacteria can influence how metformin is absorbed and metabolized.
  • Age and Hormone Levels – Age-related changes and hormonal shifts (such as during menopause or puberty) can affect insulin response and how the body processes medication.

How Genetics May Affect Metformin Side Effects

Metformin is a commonly used medication, especially for type 2 diabetes and sometimes PCOS. While it works well for many people, some experience uncomfortable side effects—and your genes could be part of the reason why. Let’s look at some of these symptoms and how your body’s natural makeup might influence them.

  • Unusual Muscle Pain: Muscle pain while taking metformin can be a sign of a rare but serious problem called lactic acidosis. Some people’s bodies process metformin more slowly, which can cause it to build up and lead to this condition. If you’re more sensitive to metformin, your muscles might ache even with normal doses.

  • Feeling Cold: Feeling cold can also be linked to how your body handles metformin. If metformin builds up in your system or affects your energy levels, you might feel chilly or have trouble staying warm. This is more likely if your body naturally clears the medicine more slowly.

  • Trouble Breathing: Difficulty breathing is another serious sign that metformin might not be agreeing with you. Some people are more prone to having low energy production in their cells when taking metformin, which can lead to breathing problems—especially if too much of the medicine stays in the body.

  • Feeling Dizzy, Light-Headed, Tired, or Very Weak: If you feel faint, tired, or unusually weak, your body might be reacting strongly to the effects of metformin. Some people experience drops in blood sugar or shifts in energy levels more easily, depending on how their body processes the medication.

  • Stomach Pain, Vomiting: Stomach issues like cramps, pain, or vomiting are some of the most common side effects. But some people feel these more intensely. Your genes may make your stomach more sensitive to metformin, leading to stronger reactions even if you’re taking the standard dose.

  • Slow or Irregular Heart Rate: A very slow or uneven heartbeat can happen if metformin affects the balance of fluids or energy in your body. If your system doesn’t handle the drug efficiently, this kind of side effect can be more noticeable.

Can You Get Tested for Metformin Sensitivity?

Some health and wellness companies offer genetic tests that look at your DNA to see how you might respond to metformin. These tests check for specific genetic differences that can affect how well metformin works for you or whether you might experience side effects.

Although these genetic tests are not yet used by doctors to officially prescribe or adjust metformin, they can still be helpful. Knowing your genetic information can make it easier to talk with your doctor and may help you:

  • Have more realistic expectations about how metformin might work for you.
  • Avoid guessing and reduce the time spent trying different treatments.
  • Lower your chances of experiencing uncomfortable side effects.
  • Think about other treatment options sooner if metformin isn’t the best fit for you.

References

 

Genetic Response to Ashwagandha

Catherine on April 3, 2025

Powdered Ashwagandha herb in a bowl highlighting genetic influence on herbal response

Disclaimer: This article is for informational purposes only and is not intended for diagnostic use. LifeDNA does not provide diagnostic reports on any traits discussed. Genetics is just one piece of the puzzle; please consult a healthcare professional for comprehensive guidance on any health condition.

Ashwagandha, often referred to as Indian ginseng or winter cherry, is an ancient herb with deep roots in Ayurvedic medicine. Known for its ability to help the body manage stress, improve energy, and enhance focus, it has gained global popularity as a natural supplement. But not everyone experiences the same results when taking ashwagandha—and that’s where genetics come into play.

Recent scientific interest has focused on how our genetic makeup may influence our response to ashwagandha. In this article, we’ll explore what ashwagandha is, its benefits, how it works in the body, and how individual genetic variations—especially in stress, hormone, and neurotransmitter pathways—can shape its effects.

What Is Ashwagandha?

Ashwagandha (Withania somnifera) is an adaptogenic herb, meaning it helps the body adapt to physical and emotional stress. It has been used in Indian traditional medicine for over 3,000 years to promote strength, calm the nervous system, and support immune function.

The active compounds in ashwagandha—known as withanolides—are believed to be responsible for most of its therapeutic effects. These compounds, like the Withaferin A and Withanone, help balance hormones, reduce inflammation, and support brain function.

Ashwagandha is typically available in powder, capsule, or extract form, often standardized to contain a specific percentage of withanolides.

What Are the Benefits of Ashwagandha?

Scientific studies have validated many of the traditional benefits of ashwagandha. Some of the most common and researched advantages include:

  • Reduces stress and anxiety: Ashwagandha helps lower cortisol, the body’s primary stress hormone, and may ease symptoms of anxiety.
  • Improves sleep: It promotes deeper and more restful sleep by calming the nervous system.
  • Supports thyroid health: It may help balance thyroid hormones, particularly in individuals with underactive thyroid function.
  • Boosts brain function: Ashwagandha enhances memory, attention, and information processing.
  • Increases energy and stamina: It supports adrenal health, which may lead to better energy levels.
  • Enhances muscle strength and recovery: Studies show it may improve muscle mass and physical endurance.
  • Improves male fertility and testosterone levels: Some trials have found it may raise testosterone and support reproductive health in men.

While these benefits are promising, individual experiences and outcomes with ashwagandha can vary. One reason may lie in your genes.

How Does Ashwagandha Work in the Body?

Ashwagandha interacts with multiple systems in the body. It helps regulate the hypothalamic-pituitary-adrenal (HPA) axis—a key stress response system—by reducing excessive cortisol release. It may increase GABA (gamma-aminobutyric acid) signaling, a neurotransmitter that promotes relaxation and reduces nervous activity. Ashwagandha also has strong antioxidant properties that protect cells from oxidative stress. It can influence the balance of thyroid hormones and testosterone, which are vital for metabolism, energy, and fertility. These actions create a wide range of benefits—but how powerfully they work may depend on your individual biology, especially your genetics.

What Is the Genetic Response to Ashwagandha?

Not everyone responds to ashwagandha the same way. Differences in certain genes can affect how your body processes or responds to the herb’s active compounds. Here are a few key genetic pathways that may shape your response:

COMT Gene – Cognitive and Mood Effects

The COMT (catechol-O-methyltransferase) gene affects how your brain breaks down dopamine, epinephrine, and norepinephrine—neurotransmitters related to mood, focus, and stress. Variants in the COMT gene determine whether you clear these neurotransmitters quickly or slowly. Fast COMT (Val/Val) types may experience more cognitive benefits from ashwagandha, such as better focus and stress relief. Slow COMT (Met/Met) types may be more sensitive and experience stronger sedative or calming effects.

NR3C1 and FKBP5 Genes – Stress Response and Cortisol Regulation

These genes are involved in regulating the body’s sensitivity to cortisol, the stress hormone. People with certain Glucocorticoid receptor gene;  NR3C1 or Immunophilin (prolyl isomerase 5) gene FKBP5 gene variants may have a heightened or prolonged stress response. Ashwagandha may help normalize cortisol levels, but individuals with dysregulated stress genes may respond more noticeably, finding it especially helpful in calming anxiety or improving sleep.

GAD1 Gene – GABA Production

The GAD1 gene codes for GAD67, an enzyme that helps convert glutamate (a stimulating neurotransmitter) into GABA (a calming one). Low GAD67 activity can lead to a state of excitability or anxiety. Ashwagandha’s ability to support GABA activity may be more beneficial to those with GAD1 variations who experience chronic stress or restlessness.

TH and MAOA Genes – Mood and Hormone Regulation

These genes affect dopamine, serotonin, and other mood-related chemicals. Variations here can influence how ashwagandha impacts mood stability, emotional resilience, and even energy levels. People with MAOA-L (low activity) may experience stronger mood-stabilizing effects from ashwagandha, especially in high-stress environments.

Where Does Ashwagandha Come From?

Ashwagandha is a shrub native to India, parts of the Middle East, and North Africa. Its roots and berries are used for medicinal purposes, although most modern supplements use root extracts. These extracts are standardized to specific withanolide content to ensure consistent potency. Top-quality sources often come from organically grown plants in India and undergo purification to remove contaminants like heavy metals or pesticides.

Can Genetic Testing Help Personalize Ashwagandha Use?

DNA testing companies now offer reports that examine your stress response, mood sensitivity, hormone metabolism, and other traits related to neurotransmitter activity. These insights can help you understand whether ashwagandha may help with stress or make you feel overly calm, how your nervous system processes stimulants and calming agents, and if you’re more likely to benefit from ashwagandha for cognitive or physical reasons. This can be particularly useful if you’ve tried ashwagandha before and noticed very mild—or very strong—effects.

Who Should Be Cautious About Ashwagandha?

While ashwagandha is generally safe, certain people should consult a healthcare provider before using it. This includes pregnant or breastfeeding women, individuals with hyperthyroidism (as ashwagandha may further increase thyroid hormone levels), people taking sedatives or thyroid medication, and those with autoimmune diseases, since ashwagandha may stimulate the immune system.

Personalized Herbal Medicine

As the field of nutrigenomics grows, more people are turning to personalized health solutions based on their DNA. Herbs like ashwagandha may become part of targeted wellness strategies, especially for addressing stress, fatigue, and hormone imbalance. By understanding your genetic makeup, you can make more informed decisions about whether ashwagandha is right for you—and how best to use it.

Ashwagandha is a powerful adaptogenic herb that can reduce stress, improve mood, and support overall health. However, not all bodies respond the same. Your genetic makeup, particularly genes related to stress hormones, neurotransmitters, and hormone regulation, can shape how well ashwagandha works for you. As genetic testing becomes more accessible, it’s now possible to tailor natural supplements like ashwagandha to your unique biology—leading to more effective and balanced wellness outcomes.

The LifeDNA Methylation Genes Report gives you a closer look at how your genes may affect your well-being. One of the key genes it covers is COMT, which helps your body break down brain chemicals like dopamine and adrenaline. These chemicals affect how you handle stress, focus, and mood. Knowing your COMT type can help you understand why you may feel calm or anxious in certain situations. The report also looks at other important genes linked to mental clarity and overall wellness, making it a helpful tool if you want to learn how your body responds to things like stress or calming herbs such as ashwagandha.

References

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