Is There a Statistically Significant Incidence of MTHFR Gene Mutations Among Individuals Who Suffer Long Term Side Effects from Isotretinoin Usage?


Mutations in the MTHFR gene are relatively common and have been well researched. Mutations in this gene are known to cause a variety of health issues including, but not limited to:

  • Mental health issues
  • Impacts to detoxification pathways
  • Fatigue
  • Hormone imbalance
  • Chronic Inflammation

Because a course of Isotretinoin (known commercially as Accutane, RoAccutane, Claravis, Sotret, Myorisan, Amnesteem, Absorica), places a tremendous strain on the body, underlying genetic variations or “mutations” may impact the body’s ability to deal with and recover from this strain.

The purpose of this study is to identify whether or not there is a statistically significant incidence of certain gene mutations, including MTHFR, in individuals who experience long term side effects from Isotretinoin. For individuals who do have MTHFR gene mutations and who suffer from long term side effects after having taken Isotretinoin, there is potential for improved health by addressing methylation issues caused by the variations in the MTHFR gene.

The MTHFR gene and others being studied in this research project have been chosen for their potential relevance to long term side effects of Isotretinoin.

What to Expect

If you already know your MTHFR status, you may choose to participate in this study without additional testing.

For everyone else, as a research participant you will be asked to provide a saliva sample, by mail, to the chosen DNA testing provider. 6-8 weeks after providing this sample, you will receive your results. You will then be asked to download your raw DNA data file and upload it to another 3rd party service provider who will generate an extensive, personalized health report which is yours to keep.

Here are some samples of some of the information included in the 132 page report you will receive (click to view, best viewed on laptop or desktop screen):

To complete the research study, you will be asked to complete an extensive, anonymous, health questionnaire. Your anonymous answers to this questionnaire will help us to look for correlations between Accutane long term side effects and the presence of specific genetic variations.

These correlations may help us to:

  • Identify and/or confirm effective healing methods and protocols for long term side effects, based on measurable genetic factors.
  • Identify measurable genetic susceptibilities for long term side effects from using Isotretinoin (Accutane). If discovered, these susceptibilities may help those most vulnerable to severe side effects avoid taking Isotretinoin in the first place.
  • Identify individuals who have recently taken Isotretinoin who may be at risk for long term side effects.
  • Identify preventative measures for at-risk individuals. (i.e., dietary and or supplementation protocols)

A Note About Recovery from Accutane Side Effects

For those struggling with long term side effects from Isotretinoin (Accutane, RoAccutane, Claravis, Sotret, Myorisan, Amnesteem, Absorica), this study is intentionally structured to help participants discover genetic information which may be useful in restoring health. As mentioned above, study participants receive the StrateGene DNA report (see sample images above) which provides personalized DNA information that may then be used in conjunction with the Accutane Recovery Stack for a multi-level, holistic approach to healing from Accutane damage. The StrageGene report may be used in conjunction with other health services and health care providers.

Study Prerequisites

Participants must have taken 13-cis-Retinoic Acid (Isotretinoin), the acne chemotherapy drug commercially known as Accutane, RoAccutane, Claravis, Sotret, Myorisan, Amnesteem, Absorica, as well as the chemical name 13-cis-Retinoic Acid (Isotretinoin). There is no time limit. In other words the drug may have been taken recently, decades ago, or anything in between. You are invited to participate whether you have noticeable side effects from the drug or not.

Study Purpose

The purpose of this study is twofold:

  1. Determine whether or not individuals who suffer from long term side effects* after having taken Accutane, have a statistically significant incidence of MTHFR gene mutations, specifically the A1298C and and C677T variants. The study also looks at genetic variations (SNPs) also called “mutations” in 77 other genes. For a complete list, please see the FAQ section towards the bottom of this page.
  2. To provide participants with potentially powerful genetic information which may be useful in mitigating long term side effects from Accutane.

* “Long term side effects” is defined as persisting after more than one year after stopping Accutane treatment.

Study Cost

If you have already been tested for MTHFR, the only requirement is to purchase the book Dirty Genes. Instructions will be provided once you register.

For those who have not been tested, the study requires the following purchases by study participants:

Part I

Part II

(purchased 6-8 weeks after Part I) has generously agreed to provide a 15% discount to study participants. Use coupon code: MTHFRSTUDY

Total estimated cost: $195.74 + tax and shipping

Study Structure & Requirements

The structure of the study involves:

  1. Participants are asked to complete a commercially available gene test (by mail).
  2. While waiting for the test results (6-8 weeks), participants are asked to fill out a questionnaire regarding general health, health history, and any experience of Isotretinoin (Accutane) side effects.
  3. Once the DNA test results are available, participants are asked to download their raw DNA data and upload it to be processed into the the StrateGene DNA report. Participants are asked to include anonymous genetic data from this report when submitting the research questionnaire.
  4. Participants who complete the study will be eligible to participate in potential follow up studies on the impacts of specific healing protocols that target long term Accutane side effects.

Participants must agree to:

  • Complete a DNA test (or provide results from a completed test).
  • Upload the raw DNA data from this test to to generate the Strategene report.
  • Complete an anonymous research questionnaire which includes current health indicators as well as health history questions.
  • Include gene data from the StrateGene report in the research questionnaire, in such a way that the gene data remains anonymous.

Additional study requirements:

  • Ability to download DNA raw data from and upload to the Strategene reporting service. (Instructions will be provided)
  • Access to spreadsheet software. Options include Microsoft Excel, Apple Numbers, Google Docs
  • The ability to open a spreadsheet in one of these programs, add your answers, save the spreadsheet and attach it to an email.
  • The ability to take screenshots on your computer and attach the images to an email.

Time to Complete

DNA Testing

Once ordered, your DNA testing kit takes 7-10 days to arrive. You’ll provide a saliva sample and mail that to Test results are then available in 6-8 weeks. For this reason, you are encouraged to order your DNA test as soon as possible if you are interested in participating in this study.


Some answers in the study questionnaire require completing exercises in the Dirty Genes book. You have 6-8 weeks to complete the questionnaire while waiting for your DNA test results.

Total Time

The DNA testing and completion of the questionnaire are all that is required of you as a research participant. Estimated time to complete is 6-8 weeks, mostly due to waiting on the DNA test results.

Anonymity & Privacy

To ensure anonymity, each participant is assigned a 5 digit number during the registration process. This number is used to correlate the research study’s anonymous questionnaire answers with future, follow up studies, if such studies are conducted. First and last name, or any personally identifying information, are not collected as part of the study.

Regarding DNA privacy, study participants are responsible for acquiring their own gene testing and test results. The research study questionnaire requires participants to share genetic data from the Strategene report in such a way that it remains anonymous.

All anonymous, collected data will be encrypted and stored on an offline data storage device. Data submitted to this study is received at a HIPAA compliant email address and is not stored online once received.

To Participate:

  1. Please read the informed consent for the study. By choosing to participate, you acknowledge that you understand and agree to the informed consent.
  2. Please register here to receive your participant ID and a copy of the study questionnaire.
  3. Order your gene test kit from as soon as possible. (It takes up to 10 days to receive and up to 6-8 weeks to receive the results.)
  4. Complete the study questionnaire while waiting for your gene test results (6-8 weeks).
  5. Once your gene test is complete, download the raw gene data from and upload it to Strategene to generate your test results. (Instructions will be provided.)
  6. You will be given instructions on how to anonymously include the relevant gene data from your StrateGene Report when submitting your completed research study questionnaire.
  7. Optional: Subscribe to the study newsletter to be notified of study progress and results. In order to maintain anonymity, study participants are not automatically signed up to this newsletter.

Are You Highly Sensitive?

If you know you are a highly sensitive person, there is an additional study involving the MTHFR gene coming soon.


If you would like to stay abreast of this research project, you can sign up for the accutane recovery newsletter here. Study participants are encouraged to sign up.

For Facebook Users

For those interested, there is a Facebook group for this research study.

How Can I Help?

One goal for this research study is to include as many Accutane users as possible. The most useful data will come from including the full spectrum of individuals who have taken Isotretinoin. Meaning, those who are suffering extreme long-term side effects to people who are not suffering at all. To that end, whatever you can do to spread the word about the study and bring in more participants is helpful. For example sharing on social media or on Accutane message boards, contacting local churches, sharing it with your friends and family, etc.

Become a Research Study Patron

As mentioned above, possible outcomes of this research study include:

  • Support for identifying effective healing methods and protocols for long term side effects, based on measurable genetic factors.
  • Identifying measurable genetic susceptibilities for long term side effects from using Isotretinoin (Accutane). If discovered, these susceptibilities may help those most vulnerable to severe side effects avoid taking Isotretinoin in the first place.
  • The ability to identify individuals who have recently taken Isotretinoin who may be at risk for long term side effects.
  • Support for identifying preventative measures for at-risk individuals.

Your patronage of the study helps to cover the costs involved and is entirely optional. If you’d like to support this research, you can make a one time or recurring donation here:

Share This Study! Choose a platform:

Help us reach the goal of 1,000 study participants.
If you know of others who have taken Isotretinoin, please consider sharing this study opportunity with them.

Frequently Asked Questions

Beyond discovering the prevalence of certain gene variations or “mutations” in individuals who suffer from long term Accutane side effects, participation in the study provides the participant with genetic information which may be helpful, or even critical, to improving health and achieving relief from long term side effects resulting from Accutane usage.

For those who are not actively suffering, your participation may help to provide information that positively impacts the lives of others to a significant degree. Data from this study may be able to help predict vulnerabilities to long term side effects from Accutane usage, as well as help predict potentially successful treatment patterns for regaining health.

The StrateGene DNA report has been specifically chosen for its integration with the Dirty Genes book by Dr. Ben Lynch, providing an extensive framework for understanding and working with DNA test results. This framework of information may be helpful to participants beyond Isotretinoin health issues alone.

There are several important considerations:

DNA Testing

The study requires that you perform a commercial DNA test via As such, you should familiarize yourself with their privacy policy and terms and conditions. Once you download the raw data from that test, you become responsible for the safety and protection of that data. (For example, destroying it, or storing it on a storage drive not connected to the internet.)

After downloading the raw DNA data, that data must then be uploaded to to generate the StrateGene Report. You should familiarize yourself with their privacy policy and terms and conditions as well before choosing to participate.

Collected Health Information

The MTHFR Accutane study questionnaire involves anonymously providing health information including health history and current health indicators. Health Insights LLC does not collect any personally identifying information in the study questionnaire.

Completed, anonymous study questionnaires are received via a secure, HIPAA compliant email account. Questionnaires are downloaded within 24 hours of receipt and deleted from the email account.

Collected data is encrypted, password protected, and stored on an offline storage device that is not exposed to an internet connection.

After careful consideration of available options, was chosen for the following reasons:

  • Reasonable cost
  • Integration with the StrateGene report
  • Superior SNP reporting over 23andMe when used as a source for the Strategene report

DNA test results from a commercially available DNA test should not be used to diagnose any condition or as a reason to make major health, dietary or lifestyle changes. If there is concern about any information in the test results, clinically administered follow up tests should be performed and confirmed or denied by a qualified health care professional.

Additionally, it must be stated that gene mutations do not necessarily impact health. In fact a gene mutation only has a 25% chance of manifesting health conditions associated with that mutation. The other 75% depends on epigenetics, that is, the expression of those genes. Gene expression is influenced by a variety of lifestyle factors including exposure to stress and toxins, diet, exercise, etc. Epigenetic factors are focused on in the Accutane Recovery Stack.

Genomics is still in its infancy. Rather than expecting exact results, the most we can hope for is to identify probabilities in terms of genetic mutations, particularly at the level of affordable, commercially available tests. For example, if a certain SNP (pronounced “snip”), let’s say the C677T variant in the MTHFR gene, comes back as homozygous (meaning one mutation from each parent), then we have one data point. Other data points regarding the MTHFR gene can be gathered by checking for health conditions that are known to correlate with that gene mutation. Still more data points can be gathered by looking at behavioral issues associated with the various genes. In this way we can get a sense of potential genetic factors at play within an individual’s physical makeup. This study uses all three of these methods.

The stated accuracy of the StrateGene report is as follows:  “The StrateGeneV1 array is a single-nucleotide polymorphism (SNP)-based assay, used to detect variants for the generation of the StrateGene report. It demonstrates a 99.98% concordance internally and 99.67% concordance with previously validated SNP-based assay.”

MTHFR and the other genes focused on in this study play critical roles in various, known metabolic pathways in the body. While no guarantees are made, by purchasing a DNA test along with the Strategene DNA report, and in conjunction with reading Dirty Genes, study participants are able to obtain a significant amount of personal health information which may be useful in improving health. This information includes recommendations in the StrateGene report on fine tuning metabolic pathways to improve health.

Participants may use the Strategene report in conjunction with the Dirty Genes book to establish a broad understanding of how genetic factors may or may not play a role in their current health condition. The Dirty Genes book also provides actionable dietary and lifestyle options based on one’s genetic profile.

Additionally, Health Insights LLC is focused, where possible, on helping study participants interpret DNA results in a meaningful way specifically with regard to recovering from long term side effects of Isotretinoin (Accutane).

The MTHFR Accutane Research Study is self-funded by Health Insights LLC. The study structure design process, administrative costs, and research hours are all donated by Health Insights LLC.

Study participants are required to purchase

  • their own DNA test from
  • their own StratGene DAN report from
  • the Dirty Genes book by Dr. Ben Lynch

For those individuals wishing to support the work being done here, donations can be made here.

Information on the the following Gene SNPs (variations or “mutations”) are collected an studied:

If you have already been tested for the A1298C and C677T variants in your MTHFR gene, you may choose to participate in the study with only the requirement to purchase the Dirty Genes book. You may however, also choose to do the DNA test and Strategene report and provide that information as well.

If, after reading through this page, you have an additional question about the study, please use the contact form on this page.


About Accutane/Isotretinoin

Isotretinoin is a retinoid form of chemotherapy that places an extreme level of stress on the human body. Depending on the dosage and length of treatment, the body may enter into a state of hypervitaminosis A, caused by ingesting 10 times the recommended daily allowance of vitamin A over a sustained period of time.

[Hypervitaminosis A] may be acute or chronic. Acute toxicity occurs after consuming large amounts of vitamin A over a short period of time, typically within a few hours or days. Chronic toxicity occurs when large amounts of vitamin A build up in your body over a long period of time. [1]

Isotretinoin (Accutane) is a Vitamin A derivative.


One of 20,000 genes in the body, the MTHFR gene is the blueprint for the MTHFR enzyme which plays a crucial role in the “Methylation Cycle.” The Methylation Cycle is a critical process occurring in every cell of the body, approximately once every second.

Some common mutations in the MTHFR gene result in an impairment of the Methylation Cycle. As a result, the body’s detoxification pathways can be reduced by as much as 90%. Neurotransmitter production can be impacted, affecting mental and emotional well being. DNA synthesis is affected. Over 200 processes in the body rely on the Methylation Cycle.

Because MTHFR gene mutations are common and impact the body’s detoxification pathways, being tested for these mutations is a foundational approach for looking at potential, underlying contributing factors to long term side effects from Accutane.

Importantly, the negative effects of MTHFR mutations can be mitigated, to varying degrees, through vitamin supplementation and lifestyle changes. In other words, if the MTHFR gene mutation is discovered, there are actionable steps to reducing the problems associated with it. These actionable steps can improve detoxification, neurotransmitter production, and improve support for the more than 200 processes in the body that rely on the Methylation Cycle.

While more protocols may be needed for healing from Accutane side effects (i.e., neurotransmitter rebalancing, restoring gut microbiome, addressing Vitamin D insufficiency, addressing fat digestion, addressing pharmaceutical overlays such as in the case of SSRI usage, etc…), knowing one’s MTHFR status illuminates potentially critical issues happening at the molecular level which, in essence, may be “jamming up” the body.

Additionally, MTHFR mutations have been implicated in over 600 different medical conditions. So the benefits of knowing one’s MTHFR status are wide ranging, even beyond recovering from Accutane side effects.