Should I Take Aspirin to Prevent Heart Disease?

Everyone knows that aspirin protects against heart disease, right?

Well, it turns out that aspirin may only protect some people from heart disease, and for others, it can actually slightly increase the risk of heart disease.  It all seems to depend on a variant of the COMT gene.

Catechol-O-methyltransferase (COMT) is the gene that codes for an enzyme that breaks down dopamine, epinephrine, and norepinephrine, as well as other substances.  There are many studies on the common genetic polymorphisms of the COMT gene, and most of the studies focus on the neurological aspects of the enzyme.

study published in the Journal of the American Heart Association looked at the effect of a common COMT polymorphism on cardiovascular disease.  The study also looked at the combined effect of the variant along with either aspirin or vitamin E and cardiovascular disease. Continue reading “Should I Take Aspirin to Prevent Heart Disease?”

Saturated Fat and Your Genes

There has been a decades-long debate about which type of fat is best: saturated fat or polyunsaturated fat. Those in the paleo and ketogenic world are quick to tout the benefits of saturated fat; the American Heart Association promotes polyunsaturated fats[ref]. And most people remain just a bit confused about the arguments on either side…

It may depend on your genes as to which answer is right for you. Individualized diet advice instead of generalities that apply to the majority!

Genetic Studies:
There have been several studies that investigated the effects of a high saturated fat diet on cardiovascular disease stratified by genetic variants. Continue reading “Saturated Fat and Your Genes”

Interaction between high fat diet, blood pressure, and your genes

ACE-deletionWondering if you should cut down on red meat and fat to lower your blood pressure? According to a new study, it could depend on your genes.

A recent study in the Journal of the American Heart Association illustrates once again the interaction between genetics and diet.  The study looked at blood pressure measurements in twins on a higher carb diet vs a higher fat.

For the first six weeks of the study, the participants, who were non-obese twin pairs, ate a higher carb diet which consisted of 55% carbohydrates, 30% fat, and 15% protein.  Blood pressure and other blood markers were measured at the end of the six weeks. For the second half of the study, the participants switched to a higher fat diet consisting of 40% carbohydrates, 45% fat, and 15% protein with the fat mainly being saturated fat from red meat, sausage, bacon, and full-fat dairy.

One parameter that was measured was the level of ACE, or angiotensin-converting enzyme, which controls blood pressure via the constriction of blood vessels. ACE inhibitors are a common type of blood pressure medication which works by decreasing or inhibiting the angiotensin-converting enzyme. The ACE gene has a common variant referred to as the ACE deletion/insertion.  To determine your variant of ACE deletion/insertion, check rs4343.

Check your 23andMe results for rs4343 (v4, v5):

  • AA: ACE insertion/insertion
  • AG: heterozygous – ACE deletion/insertion
  • GG: ACE deletion/deletion


The study found that overall, ACE levels increased by about 15% on the higher fat diet, but it did not find a significant increase in blood pressure when looking at the whole group.   When segregating by ACE genotype, the study found that those with the GG genotype (ACE deletion) had twice the average ACE increase on the higher fat diet, and they also had an increase in systolic blood pressure.


For those who have high blood pressure and the ACE deletion (rs4343 GG), this study indicates that decreasing fat intake from red meat, bacon, and full-fat dairy may help lower your blood pressure.

Other Studies:
Previous studies have linked the ACE deletion to hypertensionautism, and Alzheimer’s, but other studies showed no link to those diseases. This may be a case where the diet of those populations being studied plays a role in the genetic risk.

More to read:

High‐Saturated‐Fat Diet Increases Circulating Angiotensin‐Converting Enzyme, Which Is Enhanced by the rs4343 Polymorphism Defining Persons at Risk of Nutrient‐Dependent Increases of Blood Pressure  — Full Study

Building Up Iron: Check your genes to see how iron affects your health

Hemochromatosis is a fairly common genetic disease that causes iron to build up in the body. Knowing that you carry the genetic variants for hemochromatosis can literally add years to your life since you can prevent the buildup of iron through giving blood.

This is a personal cause for me, and getting the word out to as many people as possible is important because this is one bit of genetic information that can make a huge impact on the quality of life.

23andMe and Ancestry genetic data can tell you if you likely carry the genetic variant for hemochromatosis. Read on to find out how to check your data…

Background: What is hemochromatosis?

“Hereditary (genetic) hemochromatosis (HHC) an inherited disorder of abnormal iron metabolism. Individuals with hereditary hemochromatosis absorb too much dietary iron. Once absorbed, the body does not have an efficient way of excreting iron excesses.  Over time, these excesses build a condition of iron overload, which is a toxic [sic] to cells. Glands and organs, including the liver, heart, pituitary, thyroid, pancreas, synovium (joints) and bone marrow burdened with excess iron cannot function properly.  Symptoms develop and the disease progresses.”  Iron Disorders Institute

The most common type of hemochromatosis is Type 1, or Classic, and is usually caused by variants in the HFE gene.

Check Your 23andMe results for rs1800562 (HFE C282Y) (v.4 and v.5)

  • AA: most common cause of hereditary hemochromatosis, highest ferritin levels
  • AG: increased ferritin levels, check to see if compound heterozygous with rs1799945
  • GG: normal/ wild-type

Check your 23andMe results for rs1799945 (HFE H63D) (v.4 and v.5)

  • GG: can cause (usually milder) hemochromatosis, increased ferritin levels
  • CG: somewhat higher ferritin levels, check to see if compound heterozygous with rs1800562
  • CC: normal / wild-type

Check your 23andMe results for rs1800730 (HFE S65C) (v. 4)

  • TT: can cause (usually milder) hemochromatosis, increased ferritin levels
  • AT: possibly increased ferritin levels
  • AA: normal / wild-type

Iron Buildup in those Heterozygous for Hemochromatosis gene variants:

So you’ve checked your genetic data and found that you are heterozygous (one variant) for one of the HFE variants… While most of the official hemochromatosis sites will say that you are ‘just a carrier’, in actuality, it could be causing problems, just not to the extreme extent that being homozygous for the variant could cause.

Doctors and researchers seem to be focused (rightly so) on the long-term consequences such as liver failure and heart failure of extreme iron overload. But if you know that you genetically susceptible to building up iron, you can take action to avoid the irritations that come with too much iron, such as random joint pain, fatigue, and/or abdominal pain.

Recent studies showing higher disease risk due to HFE variants:

  • increased risk of non-alcoholic fatty liver disease [ref][ref]
  • metabolic syndrome  [ref]
  • cardiovascular disease [ref] including women with heterozygous variants [ref]
  • slightly higher risk of cancer [ref] meta-study [ref] breast cancer[ref] liver[ref]
  • musculoskeletal problems (osteoarthritis like symptoms) [ref]
  • high blood pressure [ref]
  • hyperuricemia (gout) [ref]
  • lung fibrosis  [ref]
  • diabetes[ref]
  • cardiovascular disease in kidney disease patients [ref]
  • increased lead levels [ref] [ref]

The Iron Disorders Institute includes these signs and symptoms of too much iron: chronic fatigue, joint pain, abdominal pain, liver disease, diabetes, irregular heart rhythm, skin color change, hypothyroidism, enlarged spleen, elevated blood sugar and more.


Middle-aged men and menopausal women who are heterozygous or homozygous for any of the HFE variants, should, in my non-medical doctor opinion, go get their serum iron, TIBC, and ferritin levels checked or ask their doctor to test them. In the US, you can order your own labs online through places like Ordering serum iron w/ TBIC and ferritin should give you enough information to know if you are storing too much iron.

If you have slightly elevated iron levels, the simplest way to manage iron levels is to give blood! You will probably feel good, and you will definitely help out someone else with your blood donation. If your iron test levels are really high, go to a doctor. Seriously.

Natural Iron Chelators and Inhibitors:

In addition to giving blood, natural and pharmaceutical iron chelators have been used to reduce iron levels in the body.[ref]

Quercetin, a flavonoid found in fruits and vegetables, has been studied for its iron chelating properties.[ref]  A 2017 study on dendritic (immune system) cells found that quercetin “increase extracellular iron export, resulting in an overall decrease in the intracellular iron content and consequent diminished inflammatory abilities.” And a 2014 study on quercetin concluded: “Potentially, diets rich in polyphenols might be beneficial for patients groups at risk of iron loading by limiting the rate of intestinal iron absorption.” Foods high in quercetin include apples, dark cherries, tomatoes, capers, onions, and cranberries. Quercetin supplements including pure quercetin powder are also readily available.

Another flavonoid, rutin, has also been studied for its iron chelation properties.[ref]  A 2014 study in rats found: “Rutin administration to iron-overloaded rats resulted in significant decrease in serum total iron, TIBC, Tf, TS%, ferritin levels…”  Foods high in rutin include capers, black olives, buckwheat, asparagus, and berries.  Rutin is also available as a supplement and in bulk powder.

Okra: A 2015 study found that okra “dramatically decreases intracellular iron levels in H63D cells compared to untreated cells”.[ref]  Time to make some gumbo!

Dietary phenols such as EGCG from green tea and grape seed extract also have been shown to inhibit iron uptake in the intestinal cells.  [ref]

The jury is still out on curcumin.  In a double-blind, placebo-controlled, randomized, cross-over study, curcumin was found to decrease hepcidin and increase ferritin.[ref]  Other studies, though, refer to curcumin as a possible iron chelator.[ref]

Taurine, in a mouse model of hemochromatosis, was found to protect against liver damage from excess iron.  The study is worth reading and looking into if you are worried about iron-induced liver damage.

Iron Fortified Foods…May, or may not, be a problem for those carrying the hemochromatosis genetic variants.  In the US, white rice and refined wheat products are fortified with iron.

  • A Swedish study looked at the effect of iron-fortified foods on iron absorption in men with hemochromatosis.  The study found that eliminating iron fortification from foods significantly reduced the iron absorbed by the men in the study.  The study also found that the time needed between phlebotomy (to maintain proper iron levels in hemochromatosis patients) was increased significantly.
  • A US study in 2012, though, declared that there is no evidence that dietary iron content made a difference in ferritin concentration.  (I actually don’t agree with their ability to draw that conclusion based on the method of doing the study.)  Basically, they gave 200 people (homozygous for the HFE C282Y variant and high serum ferritin levels) surveys asking for information on the type of diet they had eaten for the last few years as well as alcohol intake.    Then they compared the survey data to their serum ferritin levels to look for a correlation and drew the conclusion that iron intake doesn’t impact hemochromatosis. [ref]
  • A few studies have looked at the impact of the overabundance of iron on obesity.   But while the risk for each of these diseases increases with higher ferritin levels, no one seems to be publishing studies showing that iron fortification is causing them.

The Science behind Iron Overload:

Hepcidin is the iron regulatory hormone produced by the liver. Hepcidin was discovered and named in 2000, and scientists have since figured out that it controls the regulation of iron in the body and responds to lipopolysaccharides to prevent iron-loving bacteria from reproducing rapidly.  [ref]

“Hereditary hemochromatosis is caused by a deficiency of the iron-regulatory hormone hepcidin (Ganz and Nemeth, 2011). Hepcidin is a 25 amino acid peptide secreted by hepatocytes. It controls iron concentrations in extracellular fluid and blood plasma by regulating the amount of ferroportin, the sole known cellular iron exporter. Ferroportin transports absorbed, recycled or stored iron from tissues into plasma (Donovan et al., 2005). Hepcidin binding to ferroportin triggers its degradation, resulting in the decreased transfer of iron to plasma and consequently hypoferremia (Nemeth et al., 2004b). During infections or in response to injection of microbial molecules, hepcidin production is greatly enhanced (Armitage et al., 2011; Rodriguez et al., 2014), stimulated by inflammatory cytokines including IL-6 (Nemeth et al., 2004a; Rodriguez et al., 2014) and possibly activin B (Besson-Fournier et al., 2012). It has been proposed that hepcidin-mediated hypoferremia functions as a host defense mechanism that evolved to restrict iron availability for pathogen growth (Drakesmith and Prentice, 2012; Ganz, 2009) but this has never been demonstrated. Hepcidin was also reported to have direct bactericidal activity in vitro (Krause et al., 2000; Park et al., 2001), but the effect is seen only at unphysiologically high concentrations.” –

Other Genes Involved:

Not everyone who is homozygous for the hemochromatosis variants will develop iron overload.  Diet and lifestyle play a role in the rate at which iron accumulates. Additionally, there are other genes that play a role in ferritin levels and iron levels in the body. Some of these are listed below:

  • BMP2 gene: rs235756 (v.4)-A allele is associated with higher ferritin levels with HFE variants (several studies) [ref] [ref]
  • BTBD9 gene: rs3923809 (v.4 and v.5)-G allele is associated with higher ferritin levels [ref]
  • HBS1L-MYB gene: rs4895441 (v.4 and v.5)- G allele protects against anemia [ref]
  • SLC40A1 gene: rs1439816 (not in 23andME v.4/v.5 data) – C allele may lead to more liver damage [ref] [ref]
  • TMPRSS6 gene: rs855791 (v.4 and v.5)- G allele associated with higher iron stores in men [ref
  • SLC40A1 gene: rs11568350 (not in 23andMe data) (Q248H) – leads to higher ferritin levels

Rare genetic forms of hemochromatosis (mostly non-HFE):

  • Hemochromatosis type 2A: listed in 23andMe as i5001498 (T is the risk allele)(v.4 and v.5)[ref]
  • Hemochromatosis type 2A: listed in 23andMe as i5001502 (A is the risk allele)(v.4 and v.5) [ref]
  • Hemochromatosis type 2A: listed in 23andMe as i5001501 (C is the risk allele)(v.4) [ref]
  • Hemochromatosis type 2A: listed in 23andMe as i5000096 (T is the risk allele)(v.4) [ref]
  • Hemochromatosis type 2A: listed in 23andMe as i5001503 (T is the risk allele)(v.4) [ref]
  • Hemochromatosis type 4: rs28939076 (T is the risk allele)(v.4) [ref]
  • Hemochromatosis type 4: i5006507 (T is the risk allele)(v.4)[ref]
  • Hemochromatosis type 4: i5006505 (A is the risk allele)(v.4)[ref]
  • Hemochromatosis type 2B: listed in 23andMe as i5003867 (T is the risk allele)(v.4) [ref]
  • Hemochromatosis type 1: i5012781 (C is the risk allele)(v.4) [ref]
  • Hemochromatosis type 1: i5012784 (C is the risk allele)(v.4) [ref]
  • Hemochromatosis type 1: rs1800562 (A is the risk allele) (v.4 and v.5) [ref]

Final thoughts…

Bloodletting in 1860. Public domain photo from Burns archive.

It hit me while researching all of this, that the bloodletters of yesteryear probably did some good for the minority of people who were overloaded with iron. Leeches to reduce blood and iron stores were probably effective against bacterial infections from iron-loving bacteria.

Fortification of iron into all wheat product in the US, which began in the 1940’s, is good for children and most women of childbearing age, but it adds to the iron overload burden for some men and older women.  When looking at the forced fortification of foods with iron and folic acid, it really does seem that the policymakers are focused on the majority, at the expense of a minority who genetically are harmed by it.  Since iron can takes decades to build up in the body, it may be that we are now seeing the consequences in the baby boomer generation.


More to read:




Thiamine – Genetic Variations in Need for B1

ThiamineThiamine (thiamin), also known as vitamin B1, is a water-soluble vitamin that serves as a cofactor in the metabolism of carbohydrates, branch chain amino acids, and fatty acids.  It is essential and needed in the production of ATP, which is used in every cell for energy. Severe deficiency of thiamin leads to beriberi, and less severe deficiency can cause fatigue, gut issues, headaches, and irritability.  [ref] [ref]

Food sources of thiamin include pork, enriched rice and wheat products, wheat germ, legumes, and sunflower seeds.  Daily recommended intake is around 1.2 – 2 mg per day. For someone on a  grain free diet who doesn’t eat a lot of pork, it may be worth tracking your intake for a week or so to make sure that you are getting enough thiamine. is an excellent and free way to keep track of your nutrient intake.

Thiamine transporter gene:

An SLC35F3 (thiamin transporter) variant is linked to hypertension. There have been other studies showing that thiamine supplementation reduces blood pressure in some, possibly due to the increase in pyruvic and lactic acid found in thiamine deficiency.[ref] [ref]

  • rs17514104 (not in 23andme) –  A is minor allele.  Those homozygous for the minor allele (AA), had a significant reduction in blood thiamine content and higher blood pressure. [ref]

SLC19A2 is the gene that codes for the Thiamine transporter 1. Mutations in this gene can cause thiamine-responsive megaloblastic anemia.

  • rs28937595 – AA is considered pathogenic for thiamin-responsive megaloblastic anemia.[ref]
  • rs121908540 – TT is considered pathogenic for thiamin-responsive megaloblastic anemia. (23andMe v5 only)

Rare Genetic Disorders:

Thiamine is also involved in several rare genetic disorders.  These are usually diagnosed in infants, but those who are heterozygous for the mutations listed below may want to look into these disorders and thiamine some more.

Pyruvate dehydrogenase complex deficiency (PHDC) is sometimes responsive to thiamine.

  • rs28933391 – AA is considered pathogenic for Pyruvate dehydrogenase deficiency.
  • rs28935769 – CC is considered pathogenic for pyruvate dehydrogenase deficiency.

An inborn error of branch chain amino acid metabolism, Maple syrup urine disease,  can be responsive to thiamine.  Mutations in the BCKDHB gene cause this error in BCAA metabolism.

  • i3002808–  CC is considered pathogenic for Maple Syrup Urine Disease[ref]
  • i4000422– AA is considered pathogenic for Maple Syrup Urine Disease [ref]
  • rs74103423– AA is considered pathogenic for Maple Syrup Urine Disease [ref]

More to read:

This post is just scratching the surface of all the ways that thiamine is used in the body.

Thiamine Supplements:

If you don’t eat a lot of foods that contain thiamine, there are thiamine supplements available.  Most good B-complexes, such as Jarrow B-Right, include thiamine.  There are also individual supplements, such as Seeking Health Thiamine.  If you don’t want the extra excipients in the capsules, PureBulk also sells thiamine powder.

Vitamin C Levels and Your Genes

As the weather here turns colder, thoughts turn to preventing colds and the flu.  My “go to” method of preventing sickness has always been by loading up on vitamin C, even though recent studies haven’t really supported the idea that vitamin C increase immune function. Like most nutrients, our genes play a role in how the nutrient is transported and used by the body.

So, what happens when we take or eat vitamin C? Our bodies have vitamin C transporters that are involved in the absorption of ascorbic acid (Vit. C) in the intestines.  Most mammals actually make vitamin C themselves, but humans can’t make vitamin C and have to rely on food sources.

Vitamin C has a variety of functions in the body.  It is an antioxidant, as well as a co-factor in many important enzyme reactions, including the synthesis of collagen, carnitine, and some neurotransmitters.

There are several major diseases associated with vitamin C levels as well as with genetic polymorphisms of the vitamin C transporters, SLC23A1 and SLC23A2:

  • Higher intake of vitamin C is associated with a reduced risk of cardiovascular disease. Higher plasma vitamin C levels (whether due to genetics or due to higher fruit and vegetable intake) is associated with a reduced risk of both heart disease and overall mortality. [ref]
  • Higher intake of vitamin C is associated with a reduced risk of stomach cancer.[ref] Stomach cancer is now the third leading cause of cancer deaths worldwide.[ref]

SLC23A1 and SLC23A2 are the genes that code for vitamin C transporters.  Variants of these genes affect the plasma levels of vitamin C.  All of these variants are very common; some are associated with higher plasma vitamin C concentrations and some with lower concentrations. You can check your 23andMe results for the variants by clicking the link below (if you have received your results after Aug. 2017, use the links that say v.5).

  • rs6133175 (v. 4 only):  Those with GG have (on average) 24% higher plasma vitamin C concentrations.[ref]
  • rs6053005 (v. 5 only): Those with TT genotype allele have (on average) 24% higher plasma vitamin C concentrations.[ref]
  • rs12479919 (v. 4 only): The T allele is associated with lower risk of gastric cancer, with those carrying the TT genotype at half the normal risk of gastric cancer.[ref]  [ref]  Since higher vitamin C levels = lower gastric cancer risk, it makes sense that those people with the T allele will have higher levels of vitamin C.[ref]
  • rs33972313 (v. 5 only):  Those with a T allele have an average decrease in plasma vitamin C concentration of 24%.[ref] Another study found that those with the C allele have a reduced risk of heart disease (implied that it is due to increased vitamin C transport) [ref]
  • rs10063949 (v. 4 and v.5): The C allele is associated with decreased vitamin C transport, and also with an increased risk of Crohn disease [ref]
  • rs1776964 (v. 4 only): A study found a  higher risk of heart disease in homozygous AA women regardless of vitamin C intake. [ref]

SLC2A1 (also known as GLUT1) is the gene that codes for the enzyme that transports glucose across the cell wall.  This same enzyme also transports the oxidized form of vitamin c, dehydroascorbic acid, into cells where it is then reduced to ascorbic acid. [ref]  While there are studies linking GLUT1 polymorphisms to diabetes in some populations, I didn’t find any relating to vitamin C levels in the cell.

I did find one interesting study that I wanted to share about vitamin C, glucose, and cancer:  A study in 2015 looked at the levels of glucose and ascorbic acid in thyroid cancer cells.  “The results showed that in thyroid cancer cells high glucose inhibits both transport of AA [ascorbic acid] and DHAA [dehydroascorbic acid]. Inhibition of vitamin C transport by glucose had a cytotoxic effect on the cells. However, stabilization of vitamin C in one of 2 forms (i.e., AA or DHAA) abolished this effect. These results suggest that cytotoxic effect is rather associated with extracellular accumulation of vitamin C and changes of its oxidation state than with intracellular level of ascorbate.”

Boosting your vitamin C intake: 

The US RDA for vitamin C is 60mg per day, which is a little above what is needed to prevent scurvy (46mg/day).  The Vitamin C Foundation recommends 3000 mg/day,[ref] and the Linus Pauling Institute recommends 400mg/day.  Vitamin C is a water-soluble vitamin and non-toxic, but you (and your bathroom) will know it if you exceed your personal bowel tolerance.

Excellent food sources of vitamin C include oranges, grapefruit, kiwi, strawberries, tomato and red peppers.

There are lots of options for vitamin C supplements including liposomal vitamin C. *

More to read:
Oregon State University: Vitamin C


Adiponectin levels, food choices, and genetics

Adiponectin, a hormone discovered in the 1990’s, is secreted by adipose (fat) tissue.  It is an anti-inflammatory protein, protective against the effects of low-grade inflammation that are associated with obesity.

Although it is made in adipose tissue, those who have more fat tissue usually have lower adiponectin levels.  It is thought that the lower adiponectin levels (and thus high inflammation) are a cause of chronic issues associated with obesity.[ref]

Low levels of adiponectin have been linked to insulin resistance, diabetes, heart disease, and cancer.  [ref]

ADIPOQ gene: responsible for adiponectin creation

Some polymorphisms increase adiponectin levels, leading to lower risk of insulin resistance,  and some polymorphisms decrease adiponectin levels which leads to a higher risk of insulin resistance and diabetes.  Diet and ethnicity also seem to play a role in how these polymorphisms affect a person.

rs17300539 (T is the minor allele,  v.4 and v.5)

  • T allele= lower weight, BMI and higher adiponectin levels; benefits from a monounsaturated fat diet and MUFA > 13% cuts risk of obesity in half [ref] [ref]

rs1501299 (T is the minor allele, v.4 and v.5)

  • T allele is associated with lower adiponectin levels in some populations[ref][ref]  but is associated with higher levels in Chinese adolescents [ref]  This may be related to diet.
  • GG homozygotes have higher adiponectin levels compared to T carriers when eating a low fiber diet. [ref]

rs266729 (C is the minor allele, v.4 and v.5)

  • CC homozygous (23andMe orientation) has lower adiponectin levels  [ref] [ref] [ref]
  • For Caucasian men with GG (23andMe orientation, more common alleles), switching from a saturated fat rich diet to either a carbohydrate rich diet or a monounsaturated fat rich diet caused plasma glucose concentrations to decrease. [ref]

rs2241766 (G is the minor allele, v.4 and v.5)

  • G allele is associated with higher risk of Type 2 Diabetes in Asian populations [ref]

rs17366568 (G is the minor allele, v.4 and v.5)

  • G allele is associated with lower serum adiponectin levels in white women but not black women [ref]

What works and doesn’t work:

Increasing adiponectin levels seems like a good idea since low levels of adiponectin are a risk factor for heart disease.  But it isn’t absolutely clear that manipulating adiponectin levels will cause weight loss.

  • Orlistat (Alli) increases adiponectin levels [ref]
  • Both blueberry juice and mulberry juice increased adiponectin levels (in mice) [ref]
  • In mice, Platycodon grandiflorus root extract (Korean medicinal food) improved insulin sensitivity to activation of PPARG which upregulates adiponectin [ref]

Here are a few things that have been tested and found not to increase adiponectin levels:

  • Fish oil doesn’t seem to have much effect on adiponectin levels.
  • Green tea extract doesn’t affect adiponectin levels [ref]


Omega-3 vs. Omega-6: polyunsaturated fats and your genes

Butter is evil. Butter is the best! Only cook with Canola oil. Wait — everyone switch back to saturated fats. Olive oil, grapeseed oil, avocado oil, cold pressed, expeller pressed….  is palm oil now good?

Am I the only one who is confused by which kind of fat is the best?

It turns out, like most things, that the answer to the ‘best type of fat’ question depends on your genes.

My simplified overview of the genes involved in PUFA conversion.

Polyunsaturated Fats:
Omega-6 fatty acids are named as such because they have a double carbon-carbon bond as the sixth bond, while omega-3 fatty acids have a double bond as the third bond. Each one is metabolized in the body into other essential fatty acids. Common sources of omega-6 (as linoleic acid) in the diet include corn, sunflower, cottonseed, and peanut oils. Fats high in omega-3 as ALA include flaxseed and chia seed, while EPA and DHA can be found in fish oil.

Most nutritionists seem to agree that the ratio of omega-6 to omega-3 fatty acids is important to our health. It is thought that our ancestors in the past ate a diet with a ratio of omega-6 to omega-3 was less than 4:1. Currently, an average Western diet has a ratio of 16:1 or higher. Omega-6 fats can have both inflammatory and anti-inflammatory properties, and it is thought that the higher ratio of omega-6 to 3 is causing an increase in inflammatory diseases such as heart disease and diabetes.[ref]

There isn’t just one “Omega-6” fat. The term applies to a series of different chains of fatty acids that are changed in your body by enzymes called fatty acid desaturase (coded for by the FADS1 and FADS2 genes). For example, if you eat a plant-based oil high in omega-6 fats (sunflower, cottonseed,  corn, etc), you are consuming it in the form of linoleic acid.  Linoleic acid can then be converted by FADS1 and FADS2 (in a couple of steps)  to arachidonic acid, which can be pro-inflammatory.

Similarly, omega-3 fatty acids from plant sources usually are in the form of alpha-linolenic acid. A small percentage of alpha-linolenic acid can be changed via the enzymes produced by FADS1 and FADS2 genes into eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). DHA and EPA are touted for their effects on lowering the risk of heart disease and for their brain health benefits.

So notice that the same enzymes are involved in the metabolism of both the omega-6 and the omega-3 fatty acids. This is where the ratio of the fats in your diet comes into play. With only a limited amount of the desaturase enzymes available, a high ratio of omega-6 to omega-3 means that more of the omega-6 will be metabolized into arachidonic acid.

Genetics of Fatty Acid Metabolism:
Genes definitely come into play here.  The FADS1 (codes for delta-5 desaturase) and FADS2 (codes for delta-6 desaturase) genes have several different variants which slow down the production of the enzymes.

So what does a slowing of the production of these enzymes mean for your body? On the one hand, having less of the linoleic acid (omega-6) turning into the sometimes inflammatory arachidonic acid due to having less of the enzyme can be good. But on the omega-3 side, this situation also produces less EPA and DHA if your diet is heavy on the omega-6 fatty acids. One way around this is to eat very little omega-6 fat; another way is to directly get EPA and DHA from fish or fish oil.

Quite a few studies have found that those with variants that slow down the conversion of linoleic acid to arachidonic acid affect disease risks. A 2008 study found that those with higher arachidonic acid to linoleic acid ratios had a higher risk of coronary artery disease.[ref]  The opposite has also been found in that those with variants slowing down the FADS enzymes can have a lower risk of heart disease.

FADS1 Variants:
Note that some of these variants are considered linked, meaning that if you have the minor allele for one of them it is highly likely to have the minor allele for all of them.  

rs174546  (v.4 and v.5) – Risk allele is T.
Those with a T allele have lower enzyme activity[ref];  lower risk of coronary artery disease [ref]; lower conversion of LA to AA; minor allele benefits more from high intake of EPA and DHA to lower high triglycerides [ref]

rs174547 (v.4 and v.5 ) Risk allele is C
Lower gene expression for those with a C. [ref]

rs174537   (v.4 and v.5) Risk allele is T
Lower arachidonic acid and EPA levels [ref]; lower total cholesterol levels for the minor allele [ref] lower risk of type 2 diabetes [ref]

rs174548 (v.4 and v.5) Risk allele is G
Arachidonic acid and phosphatidylcholine is reduced in those with the minor allele[ref]

rs174550 (v.4 and v.5) Risk allele is C
Risk allele is associated with lower HDL and higher triglycerides [ref]

FADS2 Variants:

rs1535  (v.4 and v.5) Risk allele is G
A lower rate of ALA to EPA conversion in adults with the minor allele [ref]; increased DHA levels in breastfed babies with the minor allele [ref];

rs174575  (v.4 and v.5) Risk allele is G
Found to be part of a haplotype corresponding to higher linoleic acid and lower levels of arachidonic acid[ref]; several other studies on DHA in breastmilk that seem to possibly contradict each other.


Things to think about doing if you have FADS2 and FADS1 variants listed above: 

  • Reducing your omega-6 to omega-3 ratio is a good idea (cut out the fried fast food!)
  • If you have a clean source of fish, increase your fish consumption.
  • If you are supplementing with flaxseed oil or chia seeds, you may be converting very little into DHA and EPA.  A fish oil supplement may be a better way to go.

More to read:

Coffee: Is it right for your genes?

Coffee and GenesCoffee — is it good or bad for you?

Coffee is one of the most popular drinks in the world, second only to tea! It is sometimes controversial due to its caffeine content.

Large, population-wide studies have shown many benefits of coffee consumption including decreasing the risks of heart disease, endometrial cancer, diabetes, Parkinson’s disease, liver cancer, cirrhosis, prostate cancer, and stroke. But large population studies often miss an individual’s reaction to a substance (see Vitamin E, Genetics, and Inflammation), and coffee’s benefits can vary based on your genes.

Antioxidants in Coffe
Coffee is actually the “number one source of antioxidants in the U.S diet, according to a new study by researchers at the University of Stanton”.[ref] In brewed coffee, there are several micronutrients, including potassium, magnesium, and niacin, available in somewhat significant levels, but variations in soil nutrients, processing, and brewing do make a difference in the micronutrient levels per cup.[ref]

Caffeine is metabolized in the liver by the CYP1A2 enzyme (coded for by the CYP1A2 gene). Slow metabolizers of caffeine – CYP1A2*1F (rs762551 AC or CC) – have a slightly increased risk of heart attack when drinking more than 2 cups of coffee per day. Four+ cups of coffee increase the risk for heart attacks even more in slow metabolizers.

Fast metabolizers (AA) have a decreased risk of heart attack with coffee consumption, with heavy coffee drinkers having a significantly decreased risk that is about 70% less than average. In European Caucasians, the population split between fast and slow metabolizers is about even.[ref][ref]

Check your 23andMe results for rs762551:

  •  CC: Slow metabolizer of caffeine, higher risk of heart attack with more than 4 cups of coffee per day
  •  AC: Slow metabolizer of caffeine, higher risk of heart attack with more than 4 cups of coffee per day
  •  AA:    Fast metabolizer of caffeine, lower risk of heart attack with heavy coffee consumption

Changes to the adenosine A2A receptor gene (ADORA2A) also gives rise to variation in how we respond to caffeine.  One thing that caffeine does in the body is to block adenosine receptors, which are believed to play a role in promoting sleep.  Changes in the way the adenosine receptor functions, due to a genetic polymorphism, can alter a person’s response to caffeine.  [ref]

Check your 23andMe results for rs5751876:

  •  CC: no increase in anxiety from caffeine (avg.)
  •  TT:  high caffeine dose more likely to make you anxious [ref]

For those with a BRCA1 mutation, one study found that coffee consumption before age 35 for those with the C-allele reduced their risk of breast cancer by 64%.[ref]

So what type of coffee should you drink to increase antioxidants?  One recent study showed that the lighter roasts have a higher antioxidant content.  Lighter roasts also increased intercellular glutathione concentrations better than darker roasts.

Hate coffee? There may be genetics involved in that also. Check out this article on bitter taste receptors.


Looking for a way to pep up your morning coffee?  Here are a couple of options:

Include Bulletproof Brain Octane oil:

Add Lion’s Mane and Chaga mushroom extracts with cognitive benefits (my new favorite!):

More to Read:

Genetics of Cholesterol Levels

Heart disease is the leading cause of death in the US and around the world, and hand-in-hand with heart disease goes the often demonized cholesterol.  Standard medical advice on ideal cholesterol levels and cardiovascular disease is often confusing, ever-changing, and sometimes downright contradictory.

Here is a look at some of the ways our genes are involved in either high or low cholesterol levels and at the evidence from research studies on the effects of high or low cholesterol.

The “cholesterol problem”…
So what is the role of cholesterol in the body?

Cell membrane showing cholesterol molecules within the phospholipid bilayer. Wikimedia Commons.

Cholesterol is a type of lipid (fat) that is created in by all animals and is an essential part of the cell membrane structure. Every cell in our body is surrounded by a membrane composed mainly of phospholipids. Cholesterol molecules also make up part of the cell membrane, stabilizing the membrane to help maintain the integrity of it. It keeps the membrane firm enough to keep some very small water-soluble molecules out, but yet not too rigid. All-in-all, a vital component of each cell in our body.

Cholesterol is also the precursor for bile acids, vitamin D, and the steroid hormones, such as testosterone, estrogen, progesterone, cortisol, and aldosterone. Bile acids are essential to the breakdown of dietary fats, and vitamin D plays a big role in calcium metabolism and in bone health.[ref]

Like most things in the body, it is a matter of having neither way too much nor too little cholesterol. The right amount is personal to each of us, depending on our genes and our diet.

Here is an interesting chart plotting causes of death worldwide along with cholesterol levels. The chart shows a sharp increase in mortality with lower cholesterol levels. One reason for the high mortality rates with low cholesterol is that cholesterol plays a role in protecting against infectious diseases.[ref]  Don’t like charts? There is a large 10-year study out of Norway that found the lowest mortality between ~190 to 270 mg/dl (5 and 7 mmol/l).

So where does cholesterol come from?  In addition to the cholesterol that your body makes, cholesterol from food (animal products) is absorbed in the intestines.  Ingesting foods with cholesterol causes a  temporary increase in serum cholesterol levels, with levels drop to baseline in about seven hours.[study]

Eating cholesterol causes the body to produce less of it, and lowering cholesterol intake will trigger the body to make more of it. The majority of cholesterol in the body is synthesized in the liver, intestines, adrenals, and reproductive organs.  It is a multi-step, complex process. Cholesterol synthesis is regulated through several processes, with one of the main ways being the SREBP protein, coded for by the SREBF1 and 2 genes.  Other genes involved in your cholesterol levels include cholesterol transport and receptor genes.

Statins and Cholesterol Lowering Medications:
Statins, one type of cholesterol-lowering medicine,  are one of the most prescribed medications in the US and UK. It was estimated in 2014 that about 28% of Americans over age 40 are taking a statin. With prices for the prescription drugs ranging from $10 (generic) to over $700 for a month’s supply, the economic impact of taking statins can be extensive, especially when calculated over the typically many years of use.  [goodRx]

The Number Needed to Treat website has an extensive review of studies on statins, including the increased risk of diabetes and muscle pain. It is an interesting, well-crafted assessment of the risks and benefits which concludes that the risks from statins outweighs the benefits for most people.

Recent Studies on Cholesterol:

A March 2018 study found that lung cancer patients with lower cholesterol were at a 61% higher risk of death.[ref]


Genetic variants that affect cholesterol levels:

CETP Gene:
One of the well-studied genes related to cholesterol is CETP (cholesteryl ester transfer protein), which codes for a protein involved in exchanging triglycerides between LDL and HDL cholesterol.

The rs708272 polymorphism is also known as Taq1B in studies.  Those with the T (referred to as A or B2 in studies) allele generally have higher HDL cholesterol.  In research studies, the polymorphism is usually referred to as Taq1B, and B2B2  is the same as rs708272 – TT.

Check your 23andMe results for rs708272 (v4, v5):

  • TT: reduced CETP function, higher HDL cholesterol levels
  • GT: reduced CETP function, slightly higher HDL cholesterol levels
  • GG: normal type

A 2009 study investigated the effect of the Taq1B polymorphism (rs708272 – T) for both HDL levels and the risk of heart attack.  That study (18,000+ women) showed an average increase in HDL level per T-allele and reduced risk of heart attack.  A 2016 meta-study confirmed this increased HDL and reduced heart attack risk in Caucasians and Asians.

Another polymorphism of the CETP gene, rs5882 or I405V, is linked to HDL cholesterol levels and lower risk of dementia.  The 2010 study on dementia, published in the Journal of the American Medical Association, found that those with the G allele had a slower rate of memory decline and that homozygotes had a 70% reduction in risk of dementia!

Check your 23andMe results for rs5882 (v4, v5):

  • GG: higher HDL cholesterol levels, significantly lower risk of dementia[ref][ref]
  • AG: higher HDL cholesterol levels, lower risk of dementia
  • AA: normal type

One more SNP near the CETP gene also is associated with higher HDL levels.

Check your 23andMe results for rs3764261 (v4, v5):

  • AA: increased HDL cholesterol levels [study]
  • AC: increased HDL cholesterol levels
  • CC: normal type


PCSK9 Gene:
The PCSK9 gene is being studied for the effects of polymorphisms on LDL levels.  There is a fairly in-depth video with nice visuals here.  One well-studied gene variant that decreases LDL levels is rs11591147.  A 2012 meta-study showed that the T allele significantly lowers the risk of cardiovascular disease (28% risk reduction) and corresponds to a lower LDL cholesterol level (avg 16mg/dl).   This is a ‘loss of function’ mutation for the gene.

Check your 23andMe results for rs11591147 (v4, v5):

  • TT: lower LDL cholesterol, decreased risk of heart disease
  • GT: lower LDL cholesterol, decreased risk of heart disease
  • GG: normal type

Another PCSK9 variant is rs28942111, which causes a gain of function in the gene, raising LDL cholesterol levels.  The risk allele here is A, which is considered pathogenic for hypercholesterolemia. [ClinVar]

Check your 23andMe results for rs28942111 (v4, v5):

  • AT: pathogenic for hypercholesterolemia[ClinVar]
  • TT: normal type

APOB – Apolipoprotein B gene:
Apolipoprotein B is one of the main carriers of LDL cholesterol throughout the body and into the cells.  Polymorphisms in the APOB gene can lead to high LDL levels and increased risk of heart disease.  [study] [study]

Check your 23andMe results for rs693 (v4, v5):

  • AA: higher LDL, increased risk of heart disease
  • AG: higher LDL, increased risk of heart disease
  • GG: normal type

There are also several fairly rare APOB mutations that are pathogenic for familial hypercholesterolemia, a genetic form of very high cholesterol.  Familial hypercholesterolemia can significantly raise the risk of heart disease. These include:

  • i4000339 -The A allele is listed as pathogenic for hypercholesterolemia [ClinVar]
  • rs5742904 -The T allele is listed as pathogenic for hypercholesterolemia [ClinVar]
  • rs12713559 -The A allele can possibly lead to familial hypercholesterolemia

LDLR Gene:
Some fairly rare mutations in the LDL receptor gene are pathogenic for familial hypercholesterolemia. 23andMe data only covers a few of the over 400 mutations known.

  • rs2228671 – G allele is pathogenic for familial hypercholesterolemia
  • rs28942079 – A is pathogenic for familial hypercholesterolemia

HMGCR gene:
A genetic variant in the HMGCR gene affects how well people respond to statins.

Check your 23andMe results for rs3846662 (v4, v5):

  • AA: normal
  • AG: statins may not work as well
  • GG: statins may not work as well [ref]


If you have high cholesterol and are trying to avoid going on a statin, here are some diet and supplement ideas to try:

  • A whole foods diet and moderate exercise are beneficial for keeping cholesterol levels in check. Yep – standard advice to cut out pre-packaged / fried food and go out and take a walk. While the old advice to give up eggs is no longer the case, cutting out the processed food should decrease inflammation and lower cholesterol levels a bit. Interestingly, a recent study found no correlation between fruit and vegetable intake and cholesterol level.
  • Niacin (vitamin B3) has been shown to raise HDL cholesterol levels and lower LDL and VLDL levels.  There is some controversy, though, as to whether this reduces the risk of heart disease. [study] [study]
  • Omega 3 / fish oil supplements are often recommended for lowering cholesterol. The jury seems to still be out on the topic, but adding fish to your diet may be beneficial.  [study]
  • Red cabbage microgreens were found to reduce LDL levels.[study] Microgreens are very simple to grow at home in a sunny window or under a LED grow light.
  • Cholesterol is important to thyroid hormone levels and vice-versa; without enough cholesterol, you will have a hard time keeping your thyroid hormone levels at an appropriate level.  A recent study recommends that women of childbearing age should have TSH levels less than 2.5. [study] [study]
  • A recent study found that pomegranate juice raised triglyceride and LDL levels, but lowered blood pressure. So you may want to skip the pomegranate juice right before a cholesterol test.

More to read:

Updated 5/2017