CYP2C19 – Metabolizing medications

The CYP2C19 enzyme is responsible for the breakdown of several popular drugs including proton pump inhibitors (Prilosec, Nexium, Prevacid), certain anti-epileptics, and an antiplatelet drug (Plavix).  CYP2C19 is also involved in activating and breaking down some hormones such as progesterone.

There are variants of the CYP2C19 gene that cause some people to be poor metabolizers and others to be fast metabolizers. You can have increased side effects (depending on the medication) either from being a slow metabolizer or a fast metabolizer.   For example, a fast metabolizer taking omeprazole to treat h. pylori may have an insufficient response due to the drug not remaining active in the body long enough.[ref]  Alternatively, some drugs such as Plavix are converted into their active drug state through CYP2C19, and being a poor metabolizer could mean that Plavix (an anticoagulant) isn’t activated quickly enough. [ref]

Valium (diazepam) is another common drug metabolized in part by CYP2C19 (along with CYP3A4). Currently, there are no official recommendations to physicians as to reducing the dosages for poor metabolizers, but there is a box warning about CYP2C19. [ref]

A couple of SSRI’s, Celexa (citalopram), Zoloft (sertraline) and Lexapro (escitalopram), are also metabolized mainly through CYP2C19.[ref]

Approximately 10 – 20% of Asians are poor metabolizers, as are 2 – 5% of people of Caucasian descent.  Up to 20-30% of Caucasians are fast metabolizers, but less than 5% of Asians are.  So there is a wide variation on how drugs are metabolized by this gene.

Here is a complete list of drugs metabolized by CYP2C19.

Beyond Drug Metabolism:
So for a person not on any drugs, what does the CYP2C19 gene do?  Obviously, we don’t have a gene just waiting around for us to take a valium.  It is involved (minor) in metabolizing melatonin[ref] and is also involved in the metabolism of estradiol.[ref]

Poor metabolizers:  

Check your 23andMe results for rs4244285 (v4, v5):

  •  AA:  non-functioning (CYP2C19*2)
  •  AG: poorer metabolizer
  •  GG:  Normal    [ref]


Check your 23andMe results for rs4986893 (v4, v5):

  •  AA: poor metabolizer (CYP2C19*3), increased risk of lung cancer[ref]
  •  AG: slow metabolizer
  •  GG:  Normal    [ref]

Ultra-fast metabolizers:

Check your 23andMe results for rs12248560 (v4, v5):

  •  CC: normal
  •  CT: ultrafast metabolizer (CYP2C19*17), more likely to benefit from tamoxifen treatment
  •  TT: ultrafast metabolizer (CYP2C19*17), more likely to benefit from tamoxifen treatment [ref]



Don’t smoke:  If you are a CYP2C19 poor metabolizer and a smoker, you are at a 5x increased risk of lung cancer[ref] and a 17x increased risk of laryngeal cancer.[ref]

Interactions with natural substances:

  • D-limonene, a component of citrus essential oils, is also metabolized through CYP2C19.  If you are a poor metabolizer and taking a medication metabolized through CYP2C19, you may not want to take supplements or essential oils with d-limonene at the same time as the medication.
  • Inhibitors of CYP2C19 may also interfere with medications that you are taking.  Common supplements such as quercetin, berberine, and caffeic acid.[ref][ref]
  • Inducers of CYP2C19 include low-dose aspirin.[ref]

Read more: This is part of an ongoing series of posts about the CYP450 enzymes and detoxification.


Lipoprotein(a): A big genetic risk for heart disease

It is often tempting to think that people who exercise, are thin, and look healthy are at a low risk for heart disease. But beneath all the healthiness can lurk a genetically driven risk factor for a heart attack: elevated lipoprotein a.

Heart disease is the number one cause of death in the US and in most countries around the world. Statistics show that one in four people in the US will die of heart disease.

We often have a picture in our heads of someone at risk for a heart attack: obese, older man who looks unhealthy, perhaps with a stressful job. Looking at the statistics, being overweight increases the risk of heart disease by 35% and being obese (BMI >35) can double the risk.[ref] Compare this to the healthy looking person who has no signs or symptoms but yet has a 3x risk of heart attack due to a genetically elevated lipoprotein(a) — Lp(a) — level.

The Biggest Loser host and fitness trainer, Bob Harper, has been open about his recovery from a very serious heart attack that he had in 2017. He was the epitome of healthiness – fitness trainer, nutritional guru, athlete, and only in his early fifties. But he also had genetically elevated levels of Lp(a). Here is a Today show interview where he explains some of his recovery and what he is doing to prevent a second heart attack.

Family history is always mentioned by the doctor as an important indicator of your risk of heart disease, especially if you have a close family member who had a heart attack fairly young. One big way that researchers have found that family history plays a role is through the inheritance of a genetic variant that increases lipoprotein(a).

Lipoprotein(a) or LP(a) — called L P little a — is a blood particle that carries LDL cholesterol and proteins. Elevated levels of Lp(a) are a strong risk factor for having a heart attack due to atherosclerosis.  Read more about Lp(a) on the Lipoprotein(a) Foundation website.

There are questions and controversy on the role that cholesterol plays in heart disease, and that may lead people to dismiss Lp(a) as just the latest number to talk about. (Lots of people on a low carb or keto diet like to point out the flaws in the studies on cholesterol.) I think it would be a big mistake to dismiss the research on Lp(a).  There is abundant and really good research on the increased risk for heart attack, narrowing of the arteries, and stroke  (i.e. cardiovascular disease) being caused by elevated lipoprotein (a).[ref][ref]

LPA gene variants: 

The LPA gene controls the formation of the lipoprotein(a) molecule. Variants in the gene, specifically variable number tandem repeats (VNTR), cause the body to create more Lp(a). About 25% of the population carries one or more risk alleles (listed below) that correlate to the VNTR.

Check your 23andMe results for rs3798220 (v4, v5):

  • CC: risk of elevated Lp(a), increased risk for heart disease – 3.7x risk of aortic stenosis [ref]
  • CT: risk of  elevated Lp(A), increased risk for heart disease, increased risk of aortic stenosis
  • TT: normal

Check your 23andMe results for rs10455872 (v4, v5):

  • GG: likely elevated Lp(a), increased risk for heart disease – 2x risk of aortic stenosis [ref][ref]
  • AG: likely elevated Lp(A), increased risk for heart disease
  • AA: normal

Studies also showed that carrying one risk allele for both of the above — compound heterozygous — also doubled the risk of aortic stenosis.[ref]


So what do you do if you carry the risk alleles?  Knowledge is power here.

Keep in mind that this is a fairly common genetic risk factor, so it isn’t a reason to stress out or be anxious.  It is an excellent reason to do what you can from a lifestyle perspective to lower your risk of a heart attack: stop smoking, don’t drink too much, be active, eat healthily, reduce stress. You know all of these things, and now you know that they apply to you.

Get educated:
Read more about lipoprotein (a): Lipoprotein(a) Foundation,  European Atherosclerosis Society,

Talk to your doctor about getting an Lp(a) blood test done.

If you are one of those people who always ignores the “talk to your doctor” advice, you can also order a lipoprotein (a) test done through for about $45.  There are other online companies that you can order lab work through as well, and they all offer specials and coupons, so shop around.

How high is high?
One study shows a 3x risk of aortic valve stenosis for those with Lp(a) levels greater than 90 mg/dl.[ref]  Another source says normal Lp(a) levels are less than 30 mg/dl (or 75 nmol/L)[ref]  while others put it at less than 50 mg/dl.[ref] Again – this is something to talk to a doctor about and keep up with the research as it comes out.

There are a couple of therapies for high Lp(a) that have been well studied as well as new drugs coming out to target it.[ref]

  • Apheresis, where they run your blood through a machine to remove the LDL particles,  is considered effective, but expensive and inconvenient.[ref]
  • Niacin (vitamin B3) has been used for decades to lower the risk of heart disease. Studies show that 1 -3 g/day lowers Lp(a) levels by an average of 30-40%.[ref][ref][ref]  Most studies use the type of niacin that causes flushing.
  • Overall, lowering your LDL cholesterol numbers can help lower Lp(a) some since Lp(a) is the carrier for LDL. Here is a good article on it from the Cleveland Clinic.  How do you lower your cholesterol with diet? That seems to be the million dollar question.  A more whole food, plant-based diet, in comparison with a higher meat and fat based diet, works to lower cholesterol for some people.  It may be that you need to try out several diets – Mediterranean, DASH, etc – and test to see what works for your body.
  • One study showed Gingko Biloba reduced Lp(a) levels. The study used 120mg, twice a day and showed a 23% decrease in Lp(a). [ref]

More to read/watch:


HLA-B27: Genetic Variants That Increase Susceptibility to Autoimmune Diseases

Our immune system does an awesome job, most of the time, at fighting off pathogenic bacteria and viruses. But to fight off these pathogens, the body needs to know that they are the bad guys.  One part of our immune system is the major histocompatibility complex, also known as HLA, or human leukocyte antigens. The HLA genes produce proteins that, as part of our innate immune system, help our body determine what is a foreign invader that needs to be attacked.

There are many different HLA serotypes that people can have, giving us all slightly different strengths and weaknesses against microbial diseases. But along with attacking foreign invaders, a handful of HLA types also increase the susceptibility to autoimmune diseases, where the body attacks its own cells.

HLA-B27 is linked to susceptibility to inflammatory related autoimmune diseases including ankylosing spondylitis[ref], reactive arthritis, psoriasis, and inflammatory bowel disease.[ref]

Ankylosing spondylitis is a chronic inflammatory disease that mainly affects the spine.  It causes back pain and spinal stiffness, and the vertebrae can fuse together. More info can be found on the Spondylitis Association of America site.

Genetic variants included in 23andMe data that are associated with HLA-B27 are listed below.  Note that these genetic variants are not completely predictive of the HLA-B27 serotype.  These variants show if you are likely or not to carry an HLA-B27 type, but there are several subtypes of HLA-B27 and not all of them cause the higher risk of inflammatory autoimmune diseases.  A blood test is still necessary to be 100% certain that you carry the HLA-B27 type associated with autoimmune diseases.

Check your 23andMe results for rs4349859  (v5 only):

  • AA: high likelihood of carrying 2 copies of HLA-B27[ref][ref][ref]
  • AG: high likelihood of carrying 1 copy of HLA-B27
  • GG: normal

Check your 23andMe results for rs13202464 (v4, v5):

  • GG: high likelihood of carrying 2 copies of HLA-B27[ref][ref][ref]
  • AG: high likelihood of carrying 1 copy of HLA-B27
  • AA: normal

Don’t freak out if you are a carrier of HLA-B27 — certain populations have up to 20% of people carrying these variants. In Caucasians, about 10% of people carry one copy, whereas only 1% of Africans carry HLA-B27.[ref]

Although HLA-B27 dramatically increases the risk of ankylosing spondylosis over the risk that someone without this HLA type would have, ankylosing spondylosis is rare with about 1 in 2000 people having it.[ref] If you have the HLA-B27 serotype, the lifetime absolute risk is about 6%.[ref]  There are other genetic variants thought to be involved in the risk for ankylosing spondylosis,  as well environmental factors.[ref]

Interestingly, carriers of the HLA-B27 have a survival advantage for HIV and hepatitis C.[ref]

There is also a connection between HLA-B27 and changes to the gut microbiome.[ref] Spondylitis patients also showed changes in the gut microbiome with decreased F. prausnitzii and increased Bacteroides fragilis.[ref]

If you carry the HLA-B27 type and also have reactive arthritis, there is an interesting tie to salmonella persistence or other microbial infections.

Animal studies show that Lactobacillus GG probiotics may help with preventing recurrence of inflammatory bowel problems associated with HLA-B27.[ref]  Although I couldn’t find a human clinical trial on it, if you are wanting to try a Lactobacillus GG probiotic, Culturelle contains that strain.

The link between diet and symptoms of reactive arthritis or ankylosing spondylitis isn’t clear.  A meta-study looked at a bunch of studies on the subject and found no statistical links with diet. But individuals report that diet can make a difference in their joint pain with certain foods making it worse.  So trying an elimination diet or the autoimmune protocol diet may be worthwhile.



Liver Detox Genes: CYP2C9 Genotypes and Drug Metabolism

Have you ever wondered why certain medications don’t work well for you? Genetic variants can change how fast or how slow the medication is broken down in your body.

CYP2C9 is a gene that codes for an enzyme that metabolizes quite a few medications in the liver as well as linoleic acid, arachidonic acid, and serotonin outside of the liver.[ref]

Some of the most prescribed drugs metabolized with CYP2C9 include losartan (blood pressure), Warfarin, acenocoumarol, tolbutamide (Orinase), glipizide (Glucotrol), ibuprofen (Advil, Motrin), celecoxib (Celebrex), montelukast (Singulair), naproxen (Aleve).  A complete list can be found on Pharmacy Times.

There are several genetic variants of CYP2C9  that either increase or decrease the activity level of the enzyme.

This is important when looking at how your body is going to respond to different doses of common drugs.  For example, with some loss-of-function variants of CYP2C9, people may have an increased risk of stomach bleeding with NSAIDs.[ref]  Celecoxib is another drug that is metabolized by the CYP2C9 enzyme, and a new study recommends a lower starting dosage for those with reduced enzyme function.

Warfarin is a popular prescription anticoagulant, often used after strokes or for those at risk for blood clots.  Dosage variations that are determined by genetic factors are mainly based on the CYP2C9 and VKORC1 gene variants.

A popularly prescribed statin, Crestor (rosuvastatin), is also partially metabolized by CYP2C9.  A recent study found that those with slow CYP2C9 variants had more of a reduction of LDL levels when using rosuvastatin.

THC, the active component of marijuana, is partially metabolized by CYP2C9. [ref]

CYP2C9 Genetic Variants

While more than 50 variants of CYP2C9 have been found, a few of the more common variants that are available in 23andMe raw data are listed below.

Check your 23andMe results for rs1799853 (v4, v5):

  •  TT: CYP2C9*2 – poor metabolizer; 40% reduction in Warfarin metabolism [study]
  • CT:  One copy of CYP2C9*2, reduced activity
  •  CC: normal


Check your 23andMe results for rs1057910 (v4, v5):

  • CC: CYP2C9*3 – poor metabolizer; 80% reduction in Warfarin metabolism [study]
  • AC:  One copy of CYP2C9*3, reduced activity; 40% reduction in Warfarin metabolism
  •  AA: normal


Check your 23andMe results for rs2256871 (v4, v5):

  • GG: CYP2C9*9 – poor metabolizer [ref][ref]
  • AG:  One copy of CYP2C9*9, decreased metabolism
  •  AA: normal


Check your 23andMe results for rs9332131 (v4, v5):

  •  – – or DD: CYP2C9*6 – poor metabolizer[ref]
  • II: normal


Check your 23andMe results for rs28371685 (v4, v5):

  • TT: CYP2C9*11 – poor metabolizer [study]
  • CT: One CYP2C9*11 allele, reduced activity
  • CC: normal


Short-term fasting may reduce CYP2C9 activity; a 36 hour fast reduced CYP2C9 activity by 19%.  Keep this in mind if you are taking a medication that is metabolized by CYP2C9 as this can affect how long the medication is active for you.  For example, this could affect your clot time if you are taking Warfarin while fasting.

Hesperitin, a flavonoid found in lemons and oranges, is an inhibitor of CYP2C9.[ref]

Quercetin interacts with warfarin dosages, but not through CYP2C9 metabolism.  “Quercetin metabolites are able to strongly displace warfarin from HSA suggesting that high quercetin doses can strongly interfere with warfarin therapy. On the other hand, tested flavonoids showed no or weaker inhibition of CYP2C9 compared to warfarin, making it very unlikely that quercetin or its metabolites can significantly inhibit the CYP2C9-mediated inactivation of warfarin.”

More to read:


Vitamin K: CYP4F2 and VKOR Genetic Variants

VitaminK1 is a fat-soluble vitamin that is needed by our bodies to synthesize the proteins responsible for blood coagulation.  Without vitaminK1, also known as phylloquinone, bleeding is hard to control.  We get vitaminK1 from eating green plants, as phylloquinone is a part of the photosynthesis process.

Vitamin K2 comes in several different forms (MK-4, MK-7, MK-8, MK-10) and helps maintain bone strength.  Additionally, higher levels of K2 has been shown to reduce calcification in the arteries [ref], as well as possibly playing a role in mitochondrial function.[ref]

We get the highest amounts of vitaminK2 from pasture-raised eggs, dairy, and organ meat as well as from fermented soy (natto). We can also convertK1 toK2 in some organs of our bodies, and certain residents of our gut microbiome (E. coli especially) convert K1 to K2 for us.

CYP4F2 Gene:

Our body breaks down or metabolizes a lot of medications through the CYP 450 family of genes.  One of those genes, CYP4F2, codes for the enzyme that is involved in converting vitaminK1 and vitaminK2 (MK-4) to oxidized forms, thus regulating the amount available.[ref]

Genetic variation in the CYP4F2 gene causes people to naturally have higher or lower levels of vitamin K, which can affect blood clotting. Warfarin, a commonly prescribed blood thinner, works by acting on vitamin K, and CYP4F2 variants can affect Warfarin dosage levels.

Quick note of caution on Warfarin dosages: While the information provided here is based on good research studies,  you should always talk with your doctor about questions on medications.  Everyone is different and there can be more than one genetic variant affecting the metabolism of a drug. So while the genetic variants listed below may be tied to increased or decreased dosages for most people, it may not hold true for you specifically.


Because the body regulates the amount of vitamin K  via CYP4F2., someone with a genetic variant that slows down their CYP4F2 production could have higher circulating levels of vitamin K, depending on the foods that they have eaten.[ref] Thus Warfarin dosages may need to be higher for someone with an impaired CYP4F2.  (If you are wondering why there are so many studies on Warfarin, there are about 30 million people in the US prescribed the drug each year![ref])

CYP4F2 is also involved in the break down of certain omega 6 fatty acids as well as vitamin E, so it plays an important role in our body’s inflammatory response.

Check your 23andMe results for rs2108622  (v4, v5) — also known as  Val433Met or CYP4F2*3

  • TT: reduced CYP4F2 function, possibly need higher Warfarin dosages[ref][ref][ref], somewhat increased risk of stroke[ref][ref]
  • CT: reduced CYP4F2 function, possibly need higher Warfarin dosages[ref][ref], somewhat increased risk of stroke[ref][ref]
  • CC: normal

VKORC1 Gene:

VKORC1 is the gene that codes for vitamin K epoxide reductase complex subunit 1.  Basically, VKORC1 is responsible for recycling vitamin K back to the active form, which is then involved in activating clotting factors.[ref][ref]

The anticoagulant Warfarin acts on VKORC1, preventing it from activating clotting proteins.  Variants in VKORC1 then can play a big role in the amount of Warfarin that is needed.

Check your 23andMe results for rs9923231 (v4, v5)

CC: normal VKORC1 activity, increased risk of lupus (Asian population)[ref]

CT: decreased VKORC1 activity, increased Warfarin sensitivity (lower dose)[ref], increased stroke risk [ref]

TT: decreased VKORC1 activity, increased Warfarin sensitivity (lower dose)[ref],  increased stroke risk [ref]


Vitamin K is a fat-soluble vitamin, and including fat while eating green veggies will increase your absorption.  Most animal sources of vitamin K2 are naturally found with fat.

The role of K2 in mitochondrial function is still being determined, but the more recent research shows some promising results.  [ref]

Resveratrol, in high doses, may increase Warfarin’s anticoagulation activity.  This was a mouse study, though, so it may not hold true for humans.[ref]

Osteoporosis studies have shown that doses of 45mg/day of MK-4 were effective in preventing bone loss in postmenopausal women.[ref] This is a really high dose of vitamin K, but there have been multiple studies using this dose of MK-4 (mostly in Japanese women). [ref]

If you aren’t getting enough vitamin K through food sources — specifically enough vitaminK2 through pastured eggs and dairy or from natto — you may want to look into a vitamin K supplement.

While there is no known upper limit or toxicity set for vitamin K1 orK2  supplementation, there are user reviews showing that some people react poorly to too much MK-7. So just a word of warning to pay attention to how you feel if you start taking higher doses of MK-7.

Conversion of vitamin K2 in the gut microbiome is dependant on having a good gut microbiome — so if you have been on a broad spectrum antibiotic recently, your vitamin K conversion may be impaired.

More to read: 
Chris Masterjohn’s Ultimate Vitamin K2 Resource

Warfarin Dosage Calculator:
If you are comfortable with uploading your genome to Stanford, there is a nifty little calculator that gives an estimate (for informational purposes only) of warfarin dosage.

Your Drinking Genes: How well does your body break down alcohol?

Alcohol.  People have been imbibing beer and wine for millennia, enjoying alcohol ever since someone discovered the altered sensations from fermented fruits and grains.

Archeologists recently announcing the discovery of an Egyptian brewery from the time of the great pyramid.

What does alcohol do in our bodies? And why do people react differently to alcohol? (hint- it’s genetic!)

Alcohol is absorbed through the stomach into our bloodstream, making its way to our brain and to our liver.  In the liver, alcohol is first broken down with an enzyme called alcohol dehydrogenase, which helps to convert it into acetaldehyde (toxic).  Next, the enzyme acetaldehyde dehydrogenase helps convert the acetaldehyde into acetate. This is a somewhat simplified explanation, but it covers the majority of alcohol metabolism.[ref]

Alcohol dehydrogenase is coded for by the ADH genes, and acetaldehyde dehydrogenase by the ALDH genes (there are several).

There are two well studied genetic variants which have different ways of reaching the same endpoint:

~ an alcohol dehydrogenase (ADH1B) variant that speeds up the conversion to acetaldehyde, thus creating a buildup of acetaldehyde

~ an acetaldehyde dehydrogenase (ALDH2 )variant that slows down the conversion from acetaldehyde to acetic acid, again creating a buildup of acetaldehyde.

In addition to the beer, wine, and other alcohol that we might drink, the alcohol dehydrogenase enzyme also breaks down alcohols produced by bacterial fermentation in the intestines. (yep – some of your bug guts could be fermenting that apple you ate this morning.)

Retinol (vitamin A) and bile acids are also metabolized by alcohol dehydrogenase.[ref]

So what is the big deal about too much acetaldehyde? Why does it make you feel cruddy and make you flush?  Well, it is toxic and carcinogenic at certain levels.  So your body wants to get rid of it as soon as possible. Headaches, nausea… you know the drill.


ADH1B  – Alcohol dehydrogenase gene:

Check your 23andMe results for rs1229984 (v4, v5):

  • TT: faster metabolism of alcohol to acetaldehyde
  • CT: faster metabolism of alcohol to acetaldehyde
  • CC: normal

Studies of this genetic variant show:

  • increased risk of fatty liver disease with alcohol use [ref]
  • increased risk of restless leg syndrome [ref]
  • reduced risk of alcoholism (because people with the variant feel bad when they drink) [ref]
  • the variant is protective against gout[ref] (likely because people without the variant drink more alcohol, leading to gout…)


ALDH2 – acetaldehyde gene

Check your 23andMe results for rs671 (v4, v5)

  • AA: Alcohol flush reaction, much higher risk of lung cancer from smoking
  • AG: Alcohol flush reaction
  • GG: normal acetaldehyde metabolism

Studies on ALDH2 show:

  • Smokers with AG and AA have a much higher risk of lung cancer than those with GG. [ref] While smoking isn’t healthy for anyone, people with AA really, really shouldn’t smoke.
  • People with the AG and AA variants (alcohol flush reaction) are much less likely to be alcoholics.  Probably because they feel so bad when they drink.
  • Candida overgrowth also produces acetaldehyde in amounts close to those considered carcinogenic. [ref]  If you carry the ALDH2 variant and are slow to clear out acetaldehyde, you may be more negatively affected by candida.
  • A little evolutionary science:  You may be wondering why the variant is so high in the East Asian populations since it seems to be detrimental. The theory is that alcohol production (from rice cultivation) began in eastern Asia about 16,000 years ago, well before alcohol production in other civilizations. Those carrying the variant were less likely to drink a lot of alcohol, and thus were more ‘reproductively fit’, passing on the genetic variant.



The simple answer is that alcohol is a toxin for everyone. Don’t drink it – or at least don’t drink very much or very often.  (I know that most people are going to ignore me on this one :-)

MitoQ, a mitochondrial supplement,  has been shown in studies to enhance acetaldehyde clearance in the liver. “This study demonstrated that speeding up acetaldehyde clearance by preserving ALDH2 activity critically mediates the beneficial effect of MitoQ on alcohol-induced pathogenesis at the gut-liver axis.” [ref]   MitoQ is available on Amazon.

Zinc and niacin (B3) are both co-factors for acetaldehyde dehydrogenase [ref]

Glutathione is also needed for the conversion of acetaldehyde into acetic acid.  NAC is a precursor to glutathione.

H2 blockers such as Zantac and Tagamet can help reduce the flushing symptoms of the ALDH2 variant. Note that this is just helping the flushing and not moving out the acetaldehyde faster. [ref]

There is a supplement called Sunset Asian Flush that is formulated to prevent the reactions from ALDH2 variant.  It has NAC, Quercetin (a natural antihistamine), and a couple other supplements in it.

How light at night could double your risk of cancer.

The World Health Organization listed ‘light at night’ as a possible carcinogen in 2007. That is an eye-opening statement for something that affects almost all of us. From streetlights to the lamp in the living room, from accent garden lighting to the glow of TV’s and cell phone… artificial light at night is truly ubiquitous.

An often stated fact is that 80% of people in North America cannot see the milky way at night.  What was more surprising to me was that the Milky Way was supposed to be visible!  Who knew?  Oh, wait – people who don’t have light pollution know…

So how can light possibly be a carcinogen? Will turning on the TV or a light in the living room after dinner suddenly cause cancer?  Let me start with two recent, contradictory studies, and then I’ll get into the science of why I think that artificial light at night is a fundamental health problem. 

A few weeks ago a study was released that looked into breast cancer incidences and light at night in Israel.  The study used spectral imaging – a satellite mapping method that looks at the color spectrum of light – to investigate a link between wavelengths of light and breast cancer.  This was based on animal studies that showed that shorter wavelengths (the blue end of the light spectrum) were associated with increased breast cancer. The researchers factored in the socio-economic impact, age, ethnicity, and other environmental factors that increase the risk of breast cancer.  The study showed that rather than all light at night being associated with increased breast cancer risk, only areas with more light in the blue wavelengths were at an increased risk. [ref]

Not all studies agree that light at night impacts cancer risk, of course.  Another study published in February 2018 showed that exposure to light at age 20 didn’t increase the risk of breast cancer. I did see a few flaws in the study…  The participants were women in their mid-40’s who were asked to report on how much light they were exposed to at night when they were 20.[ref] I’m a woman in my mid-40’s, and I have no idea what my light exposure at night was when I was 20.  I probably would have said it was dark at night.  In fact, up until a year or so ago when I finally installed blackout curtains, I had no idea what sleeping in the true dark really felt like.

Studying light exposure at night is difficult and hard to prove causation for cancer. The majority of the world is exposed to more and more light at night. Ubiquitous. While hormone-related cancers have risen over the last fifty years,  a number of other things we are all exposed to – like endocrine disrupting chemicals – can also be linked to cancer.

Let me dig into the research a little more and explain why light at night is most likely a carcinogen, and then I’ll put it into perspective, showing how large the risk is so that you can decide if it is something you should actually do something about.

Melatonin and cancer:
Melatonin, which most people think of as ‘the sleep hormone’, rises at night and falls during the daytime. This is a circadian rhythm that is maintained in most animals, and it is governed by light hitting the retina of the eye. Even in nocturnal animals, melatonin will rise at night.

Melatonin, though, is not really a just sleep hormone. In addition to circadian signaling, recent research shows that melatonin acts as an antioxidant, helping to repair our cells at night. While we sleep, our cells go into rest and repair mode, cleaning up the waste from the active period during the day.

Two factors govern melatonin: light during the day and absence of light at night.

Melatonin levels are affected by the amount of light (specifically in the blue wavelengths) that you get during the daytime.  A June 2018 animal study on liver cancer found that increasing blue wavelengths (465-485) during the day increased nighttime melatonin levels by 7x compared to the animals kept under standard fluorescent lighting. The animals exposed to the blue-enriched light also had markedly reduced tumor growth. The daytime blue light exposure and increased nighttime melatonin decreased the Warburg Effect, which is the shift to glycolytic metabolisms that cancer cells exhibit.[ref] Other studies have shown similar increases in melatonin and decreases in tumors (prostate, oral, breast).[ref][ref][ref]

The rise in melatonin at night is governed by the lessening of the blue light hitting our eyes in the evening hours. As the sun heads towards the horizon, we get more of the red end of the light spectrum. The golden hour.  In studies, the rising of melatonin levels is referred to as ‘dim light melatonin onset’.

While suppressing melatonin with lots of blue light during the day is good, at night, we need melatonin levels to rise so that our body can clear out bad cells and fight off cancer.

Studies over the last twenty plus years have made it clear that light at night (dim or bright) causes a decrease in melatonin levels, and animal studies show without much doubt that the decreased nighttime melatonin levels increase the risk of certain types of cancer. [ref][ref][ref][ref][ref]

Human studies for cancer are based on looking at the environmental factors (in this case either light at night or lack of light during the day) and then correlating them with an increase in risk. We, of course, can’t do human trials to intentionally test a condition to cause cancer, so there always seems to be a little wiggle room to be hopeful and say “maybe light doesn’t affect humans like it does all other mammals”. The overwhelming evidence of a link between light at night and cancer, though, really means that we need to pull our heads out of the sand on this topic and take a real look at the impact on our health.

Night shift workers have an increased risk of breast cancer:
Evidence from studying shift workers (mainly nurses) showed varying results for the increased risk of breast cancer.  One large study found a 79% increase in breast cancer risk for women working the night shift for 20 years, [ref]   while another look at the combined data from the Nurses Health Studies found that for women exposed at younger ages to night shift work (light at night) there was a more than doubled risk of breast cancer.  [ref] But not all studies show such a large risk, with one estimating only a 7 – 21% increase in risk. [ref]

What about the risk from general light at night (street lights, lights at home)?

It turns out that you don’t have to work the night shift to have an increased risk of cancer due to light at night.  A California study of over 100,000 women found a 34% increased risk of breast cancer for premenopausal women exposed to higher amounts of light at night.[ref]

There are quite a few smaller studies on breast cancer and light at night with similar findings to the larger ones – with a few interesting tidbits thrown in.

One study found a 51% increased risk with higher ambient light at night.[ref]   It also found that sleeping longer (thus more melatonin) cut the risk of breast cancer in half.

Closing the shutters at night (shutting out the streetlights) was also associated with a significant decrease in cancer risk.[ref]

Why does a dim light at night matter?  You have your eyes closed when you sleep, right.

A study from a few years ago tested a light device to see if they could shift melatonin levels while the participants were asleep.  The researchers used sleep masks with different colored led lights built into them; the lights turned on for two seconds every minute for an hour while the study participants slept. The results showed that blue wavelengths through their closed eyelids had an effect on melatonin – actually shifting the time that melatonin onset began the following night. [ref]

How much light is too much?  The answer may surprise you…  Even 0.2 lux (way less than a nightlight) was found to affect cancer rates in rats.[ref]   Most studies on dim light at night use 5 lux, which would be about the amount of light from having a nightlight out in the hall near your bedroom.  To put this in perspective, on a sunny day the outdoor illuminance can be as high as 120,000 lux, and a cloudy day is about 1,000 lux. Contrast this with a moon-lit night which ranges from .002 lux to .25 lux (quarter moon vs full moon).

Beyond melatonin:
In addition to affecting melatonin levels, light at night also increases cancer risk through activation of stress hormones. [ref]  The connection between an increased risk for hormonal cancers and salivary cortisol levels has been well established, and disruption to the normal circadian rhythm of cortisol is linked doubling the risk of death in breast cancer. [ref]

So there is a bit of a double whammy here: light at night decreases melatonin (cancer preventative) and increases stress hormone levels (cancer causing).

Quantifying the risk:
So after all of the studies (and there are hundreds more than I’ve referenced here), what is the consensus for the cancer risk from light at night?  The World Health Organization and the American Medical Association both place light at night as a probable carcinogen.  Probable, though, is a word with wiggle room.

The problem with quantifying the impact of light at night is that it is pretty much everywhere.  There are a few darker spots left, though, around the world. A  study looking at artificial light levels in protected or natural areas (such as forests, conservation areas, etc)  in 158 different countries and compared the cancer incidences to areas with high light. The results of the study, when all confounders were taken into account, showed that colorectal, prostate and breast cancer risk increased by up to 35% with light at night. [ref]

What does a 35% or 79% or 2-fold increase (depending on the study!) in breast cancer risk really mean? The lifetime risk in the US of breast cancer for women is 1 in 8, with the risk increasing with age. [ref]  So a 35% increase is going to change that risk to about 1 in 6, while a 2-fold increase would increase the lifetime risk to 1 in 4.  Putting this into perspective against other known breast cancer carcinogens: hormone replacement therapy increases the risk of breast cancer by 75% (~1 in 5) [ref]; BRCA1/2 gene mutations can increase risk of breast cancer to about 1 in 2.[ref]  So light at night is not as risky as carrying the BRCA mutations, but possibly as risky or riskier than hormone replacement therapy.

Why is no one else talking about this?
There are a few articles here and there in the mainstream media on the topic of cancer and light at night, mostly when a new study comes out. And there are a few health gurus that have started talking about the impact of light at night.  The problem is that the topic gets lost in the swirl…

This topic isn’t sexy or exciting, and, quite frankly, blocking blue light at night is inconvenient. No one can make a profit by telling people to turn off their lights and go to bed.  No one wants to listen to that – sounds like just some hippie-dippie wacko stuff.  But there is more research on this topic than pretty much anything else that I’ve blogged about. The science is real. And it is time to take it seriously.


Simplest: get as much light as possible during the day.  Go outside in the morning when you get up.  Have your cuppa tea or coffee outdoors.  A recent study also showed that blue light emitting bulbs during the day help increase the production of melatonin at night. [ref]

Also simple, but sometimes kind of geeky/not cool: wear blue-blocking glasses in the evening starting a couple of hours before bedtime. Many studies show that wearing blue-blocking glasses in the evening increase melatonin production and sleep quality and quantity. [ref][ref]

Alternative to blue blocking glasses: shut off all your lights at night and go back to using candlelight.  Yeah — probably not realistic.  So get yourself some blue blocking glasses and join the dork club.

Curtains: Get some curtains and sleep in the dark. True dark is needed, so get blackout curtains or perhaps curtains over blackout shades.  Also get rid of all the little lights in your bedroom from LED indicator lights.  A little bit of black electrical tape will block them out.

A cell study found that curcumin in combination with melatonin killed bladder cancer cells.  So perhaps taking curcumin at night before bed would increase its cancer prevention ability.[ref]

Resveratrol, in combo with melatonin, was somewhat effective in reducing tumors in rats. Taking resveratrol at night may boost its benefits.[ref] Resveratrol and melatonin both boost sirtuin 1, an enzyme vital to cellular function and longevity.[ref]

Melatonin pills:
If melatonin is so great, why not just take a pill instead of producing it yourself naturally? Melatonin as an adjuvant to chemotherapy has been shown to be helpful and something to talk with your oncologist about if you are currently doing chemo.[ref][ref]  The problem with just popping a melatonin pill for the rest of us is that a big single dose isn’t what your body needs/expects. The natural rise and fall of melatonin that your body produces without light disruption is just plainly better, so your better option is to block out the blue light. Additionally, people react to the hormone differently, and your natural production of melatonin may decrease with supplementation.

Food sources of melatonin:
Almost all plants contain small amounts of melatonin which acts as an antioxidant in the plant. Pineapple, oranges, and bananas all have been shown to significantly increase serum melatonin levels.[ref] The flip side of this is that you really shouldn’t eat at night due to a circadian drop in insulin sensitivity.

Genetic variants that increase susceptibility to Lyme disease

Lyme disease is caused by being bitten by a tick that carries the bacterium Borrelia burgdorferi  in North America or other Borrelia species in Europe.  General symptoms after being bitten can include a bulls-eye rash, fever, headache, pain, and general malaise. The majority of people recover after a few weeks, but some have symptoms (neurological, cardiovascular, fatigue, arthritis) that can last for months or even years.

Whether you are one of the ones who recover quickly or have chronic symptoms including joint pain or arthritis may be due to genetic variants that you carry.

Immune Response:
The innate immune system reacts quickly to pathogens, giving us the initial inflammatory response to fight off bacterial invaders.  One part of the innate immune system is the toll-like receptor (TLR) family, which helps the body to recognize specific bacteria, like Borrelia.

The simplified picture is that the innate immune system recognizes the Borrelia bacteria, raises an alarm bringing in inflammatory molecules to destroy it. It is the front line of the body’s army, quick to rise and fight a short battle.

Part of our individuality is found in different genetic variants in our innate immune system. It makes sense for a population to carry different variants – some may be better at fighting off leprosy, others good at surviving cholera.  While variation is good on whole, for an individual, though, it can end up causing increased susceptibility to a pathogen like Borrelia.

TLR1 (Toll-like Receptor 1) -Check your Genetic Variants:

One variant in TLR1, rs5743618 or T1805G, causes a decreased TLR1 functionality for people carrying the CC genotype.  This is an advantage when it comes to leprosy and cuts the risk of severity. [ref] But when it comes to Lyme disease, this variant is linked to an increased risk of ‘antibiotic refractory Lyme arthritis’ which basically means that joints still ache after taking several rounds of antibiotics.[ref]

The C variant for rs5743618 is found in about 50% of the Caucasian population, less than 10% of African populations, and is rarely found in Asian populations. [ref]

Check your 23andMe results for rs5743618 (v4, v5)

  • CC: 1.9x more likely to have antibiotic-refractory Lyme arthritis (but better off if you get leprosy)
  • AC: normal Lyme risk
  • AA: normal Lyme risk

There is another (uncommon) TLR2 genetic variant that is not covered by 23andMe testing. It is interesting because it cuts a person’s risk of Lyme disease by more than half and reduces the risk of long-term effects from Lyme even more substantially.[ref] This again shows the impact that our genetic variants in our immune system can have on our susceptibility to diseases.

HLA-DRB1 gene:

The HLA genes code for another part of our innate immune system known as the major histocompatibility complex. One variant, HLA-DRB1 *0401 has been linked to a greater susceptibility to antibiotic-resistant Lyme arthritis as well as being a risk factor for rheumatoid arthritis.[ref][ref][ref][ref]

So why am I going on about the link to rheumatoid arthritis, an autoimmune condition? There have been quite a few different studies over the past 20 years looking at the link between Borrelia infection and subsequent autoimmune diseases. There doesn’t seem to be a smoking gun study that definitively shows Borrelia causing autoimmune diseases (that I could find), but an interesting 2017 study looked at patients with Lyme arthritis who were diagnosed with autoimmune joint diseases within 4 months of getting Lyme.  The study results showed: “Most systemic autoimmune patients had positive tests for B. burgdorferi IgG antibodies by ELISA, but they had significantly lower titers and lower frequencies of Lyme-associated autoantibodies than LA patients. Prior to our evaluation, the patients often received additional antibiotics for presumed Lyme arthritis without benefit. We prescribed anti-inflammatory therapies, most commonly disease modifying anti-rheumatic drugs (DMARDs), resulting in improvement.” [ref]

HLA-DRB1 *0401

Check your 23andMe results for rs660895 (v4, v5):

  • GG: increased risk of Lyme arthritis, rheumatoid arthritis.
  • AG: increased risk of rheumatoid arthritis
  • AA: normal risk


Other factors affecting Lyme:

A study found that age is a factor in susceptibility to Lyme with elderly people likely to have a less vigorous immune response to the pathogen. The study also found that BMI, gender, vitamin D levels, and previous exposure to Borrelia had no effect on Lyme susceptibility.[ref]


Antibiotics are, of course, the first line of defense against Borrelia. Your doctor can give you more information on the effective antibiotics.

Below are some herbal remedies that are often recommended for chronic Lyme symptoms that persist after antibiotic treatment:

Stevia, an herbal sweetener, has been shown in the lab to kill Borrelia about as well as antibiotics do.[ref] I question whether this holds true in people rather than just in Petri dishes. But if you like stevia, it is probably a safe bet to use it when you have Lyme disease and it may help.

Andrographis paniculata is an Asian herb used in traditional medicine for respiratory infections and other ailments. It is recommended as an herbal remedy (combined with other herbs) for chronic Lyme disease.  While I didn’t find any studies on its effectiveness against Borrelia, there are quite a few studies on it for other diseases.  Studies have found it to be somewhat effective in the treatment of ulcerative colitis,  changing TH1/TH17 immune response, decreasing fatigue from MS, and as an antibiotic. [ref][ref][ref][ref]

Cat’s Claw (Uncaria tomentosa) is a traditional Peruvian herbal medicine that is often suggested for Lyme disease.  Again, I didn’t find any studies specifically showing that Cat’s Claw was effective for chronic Lyme disease symptoms. Studies do show that it is an antiviral and immunomodulator and that it may be effective for Dengue fever. Other studies show it affecting TNF-alpha and IL-1B levels in the immune response.[ref][ref][ref] You can get Cat’s Claw on Amazon or at most health food stores.

Japanese Knotweed (Polygonum multiflorum) is traditional Chinese herbal medicine sometimes recommended for Lyme. No Lyme specific studies, but there is a very good review of the effectiveness and safety of knotweed for a variety of ailments. Two constituents of knotweed are resveratrol and emodin.[ref]

Emodin, found in knotweed (above), is an anthraquinone that has been shown in a cell study to be effective against Borrelia.[ref] It is also found in rhubarb and is what causes the ‘gastrointestinal effects’ from eating too much rhubarb at once. Another source for emodin is cascara sagrada (also a laxative). There are quite a few studies on emodin, and it is possibly effective as an antimicrobial and as an anticancer agent. Studies also show that long-term, high doses may not be completely safe — so read up on it and know what you are getting into before you go overboard on this one.[ref] [ref]

All in all, there isn’t a ton of research on herbal remedies for chronic Lyme disease, even though there is a lot of discussion on various websites touting their effectiveness (and sometimes selling the products).  My guess is that emodin may be the most effective constituent of some of the herbal remedies.  Rhubarb pie with some stevia?

Dads matter: MTHFR variants in fathers affect miscarriage risk

There are quite a few studies showing that women carrying certain MTHFR variant combinations are at a somewhat higher risk for miscarriage, but I recently ran across a study that added a new twist to the topic.  It turns out that the father’s MTHFR variants can also play a role in recurrent miscarriages.

The study from 2015 looked at 225 couples with more than three consecutive pregnancy losses compared with 100 control couples with successful pregnancies.  All 225 mothers in the pregnancy loss group carried either compound heterozygous MTHFR C677T and A1298C variants or homozygous C677T or homozygous A1298C. The study defined carrying just one copy (heterozygous) of either C677T or A1298C as being at a low risk for miscarriage.

When the researchers looked at the fathers MTHFR variants, they found that in the pregnancy loss group the men were more likely to carry the risk variants.[study]  This backs up the work of other, smaller studies that also found that the male’s MTHFR status combined with the mother’s MTHFR variants does seem to statistically increase the risk of miscarriage.[study]



How to check your MTHFR variants on 23andMe

Check your 23andMe results for rs1801133 for the MTHFR C677T:

  • GG: normal (wildtype)
  • AG: one copy of C677T allele (heterozygous), MTHFR efficiency reduced by 40%
  • AA: two copies of C677T (homozygous), MTHFR efficiency reduced by 70 – 80%


Check your 23andMe results for rs1801131 for the MTHFR A1298C:

  • TT: normal (wildtype)
  • GT: one copy of A1298C allele (heterozygous), MTHFR efficiency reduced
  • GG: two copies of A1298C (homozygous), MTHFR efficiency reduced




There are a couple of things that could be going on here:
First, fathers who carry the MTHFR variants are likely passing them on to the baby.  There are a couple of studies showing that the baby’s MTHFR variants may play a role in miscarriages, but there are other studies showing no effect from the baby’s MTHFR gene. Overall, the meta-studies tend to show little to no effect from the baby’s MTHFR status, so this is probably not the reason.[study]

The second possibility of why the father’s MTHFR variants matter could tie in with the fact that men carrying homozygous MTHFR variants are also at a higher risk for infertility.  A meta-analysis pooled the results of 20+ studies and showed that men carrying either the homozygous MTHFR C677T or A1298C variants were at a higher risk for infertility (29 – 63% increase).  Statistics here…  Keep in mind that this is the just the increase in the risk of infertility compared to the normal risk. For example, if the risk of male infertility is 1 in 20, a 69% increase would make the risk 1.69 in 20.[study]

Dads matter – in conception, pregnancy, and throughout life! It is easy to see how prospective moms need to clean up their diets, exercise, and sleep well before getting pregnant, but I think these studies are a good reminder that prospective fathers need to pay attention to their own health as well!

MTHFR variants (read more here) increase the need for ensuring adequate folate consumption. This means leafy green veggies, legumes, and other organic food sources of folate need to be eaten daily. If you won’t make the necessary dietary changes, there are methyl folate supplements as well. A quality B12 is also important, and many people find it convenient to take a B-complex to cover all the bases.  Here is one that I like: Jarrow B-Right. But you may find other options that are a better fit for you.

This may be a ‘talk to your doctor’ situation if you have a physician working with you on family planning.  I know – telling some guys to talk to a doctor is like banging your head against the wall, but if recurrent miscarriages or infertility are a problem, this really may be a time to get some professional help.

I didn’t find any specific studies looking at men supplementing with folate for recurrent miscarriage, but there are studies showing that it is effective for women. One recent (small) study found that 5mg of methyl folate along with B6 and B12 decreased the risk of miscarriage.[study]

Please note that methyl folate is likely the better form of supplemental folate vs. folic acid,[study]  but that some studies show that a folate-rich diet is as effective as either methyl folate or folic acid. [study]  One reason for methyl folate instead of folic acid is that there have been several recent studies linking high doses of folic acid to things like an increased risk of allergies[ study] and some epigenetic changes that are a bit of an unknown.[study]

Studies on miscarriage risk for women carrying MTHFR variants:




Review of 23andMe’s GrandTree Feature

Ever wonder whether you get your red hair from your grandmother or grandfather? Is it grandma’s fault that you are likely to go bald?

The GrandTree feature on 23andMe allows you to link together three generations to see what a grandchild inherited from their grandparents. This seems to be the ultimate way to know who to blame for

The GrandTree feature starts off by giving a great explanation of how inheritance works – and why grandchildren don’t necessarily have exactly 25% of their grandparent’s DNA.

Part of the explanation of recombination from 23andMe’s GrandTree


Once you have all everyone sharing their reports with each other, it is easy to go in and select who occupies each branch of the tree.  The Total DNA Inheritance option shows how much DNA each grandchild shares with a grandparent. For example, this ranges, in the case of my kids, between 21 and 31%.

If you have the health reports for everyone included in the sharing, you can also see some fun health and trait sharing information. Highly important information can be gained — such as who to blame for your unibrow genes or from whom your cheek dimples are likely to have come.

None of the traits are highly impactful or vitally important, but it is fun to see how inheritance works in a nice visual format.  One nice feature is to be able to trace a particular gene; if there is one particular gene that interests you, you can trace it back to see which grandparent it came from.


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