A gene variant that leads to increased sweets consumption and decreased fat (Patreon post)

Is it possible to eat more sweets and have a decrease in fat?

A new study recently published in the journal Cell shows a genetic link to having a sweet tooth, but this sweet tooth gene comes with a nice twist: it causes a slight decreased in fat mass.

I may have to dub this the ‘not fair!’ gene variant since I don’t have it.

The gene in question is FGF21, which codes for a hormone that is created in the liver. In addition to stimulating adipocytes to uptake glucose, FGF21 also is involved in signaling in the hypothalamus to suppress sugar intake and alcohol consumption. [ref]

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Are you at a higher risk for diabetes? Check your TCFL72 variants

Type-2 diabetes affects about 9% of the US population and millions other world-wide. In those over age 65, one in four people has type-2 diabetes. While the overall numbers are a bit staggering, it is interesting to note that the peak for new cases was in the ’90s with a decrease in cases from 2005-2017.[ref]

Diabetes is thought to be caused partly by environment and partly due to genetics. Genetic susceptibility has been linked to a number of different genes, but one that stands out as being particularly relevant to almost all populations is the TCF7L2 gene.

The TCF7L2 (transcription factor 7-like 2) gene is involved in the regulation of blood glucose level with insulin by affecting the expression of pro-glucagon.  Variants in TCFL2 are tied to type-2 diabetes, obesity, higher BMI,  and larger waist circumference. The SNPs listed below have been found to up-regulate TCF7L2 in pancreatic beta cells.[ref]  The up-regulation is thought to impair insulin secretion from the beta cells rather than causing insulin resistance. [ref] [ref]

Why is this important? If you have one of the TCF7L2 variants that increase your risk of diabetes, there are lifestyle and diet choices that have been shown in studies to negate that increased risk.

Genetic Variants in TCF7L2:

Check your 23andMe results for rs7903146 (v4, v5):

  • CC: normal
  • CT: increased risk for type-2 diabetes, higher glucose levels,
  • TT: strong tie to increased risk for type-2 diabetes [ref][ref][ref] [ref] and higher glucose levels [ref]

Studies on this variant have found:

  • A higher intake of omega-6 polyunsaturated fats caused T allele carriers to have higher fasting glucose and a higher risk of metabolic syndrome. [ref]
  • T allele carriers are at an increased risk of gestational diabetes.[ref]
  • Several studies have shown that people with the T allele have higher fasting or night time glucose levels. [ref][ref]
  • A Mediterranean diet normalized the blood glucose level for those with the risk genotype. [ref]
  • A study of Indian diabetics found that 70% of patients with the GT or TT genotype who took a sulfonylurea (diabetes medication type) failed to achieve the therapeutic target (compared to 19% with the GG genotype). [ref]

Check your 23andMe results for rs12255372 (v4, V5):

  • GG: normal
  • CT: increased risk for type-2 diabetes
  • TT: increased risk for type-2 diabetes[ref]

Studies on this variant have concluded: 

  • While net carbohydrate intake made no difference, high glycemic index or glycemic load caused an increased risk for TT individuals in regards to metabolic syndrome[ref]
  • A low-fat diet was found to work better to decrease BMI and fat mass for those with the TT genotype [ref]
  • Those on a low-fat diet lost more weight with the TT genotype. [ref]
  • Hispanics with the minor allele have a lower avg BMI, thus showing that the effects could be population specific since most of the larger studies were predominantly Caucasian European populations. [ref]
  • A study found that people eating a low amount of fat along with the T allele had the highest HDL cholesterol levels, while those eating higher fat diet had lower HDL levels. [ref]

Check your 23andMe results for rs4506565 (v4, v5):

  • AA: normal
  • AT: increased risk of type 2 diabetes
  • TT: increased risk of type 2 diabetes[ref] [ref][ref]


Cut out fried food: Quite a few studies (above) looked at the amount and type of fat and the effect on the risk of type 2 diabetes. Overall, decreasing fat, specifically omega-6 polyunsaturated fats such as sunflower, safflower, corn, cottonseed, sesame, soybean and peanut oils, seems to reduce the risk of diabetes for those with the risky genotypes.

Check your glucose: The above variants can lead to higher fasting blood glucose levels.  Blood glucose meters aren’t expensive and are widely available. Watch your glucose levels and look into a lower glycemic index diet. Everyone has individual differences in how their blood glucose levels change in response to foods, so regular testing can help you know if you are on the right track.

Blame your mom: Inheriting the TCF7L2 variants from your mother instead of your father may increase your risk of diabetes.  [ref]

More to read:

Color TV has made us fat: melatonin, genetics, and light at night

Diet – Gene Interaction in Type 2 Diabetes Risk




Meat consumption, colon cancer, and your genes

The link between colon cancer and meat consumption has been trumpeted by vegetarians and heatedly refuted by paleo fanatics. My question, as usual, is: “What role does genetics play?”

The World Health Organization includes processed meat on their list of probable carcinogens, based on several large epidemiological studies. According to the American Cancer Society, the lifetime risk of colon cancer is around 5%, and increasing that risk by around 20% would give a lifetime risk of about 6%.

Genetics study:
A 2014 study looked at the interaction between genetics and the risk of colon cancer from processed meat.  The study was conducted with over 9,000 people with colon cancer who were compared to 9,000 control subjects without colon cancer. The study found that the increased risk of colon cancer from meat consumption was limited to those with a certain genetic variant in the GATA3 gene.

Check your 23andMe results for rs4143094 (v.5 only):

  • TT: higher risk of colon cancer with increasing meat consumption
  • GT: higher risk of colon cancer with increasing meat consumption
  • GG: normal

The increase in the risk of colon cancer for those with the T allele did vary by the amount of meat consumed.  Those with the highest consumption of meat and a T allele were at a 39% increased risk for colon cancer, while those with lower meat consumption were at a 20 – 26% increase in risk.

People who carry the GG genotype, which is about 60% of Caucasians and 90% of Chinese populations, were not found to have an increased risk of colon cancer with meat consumption.  This actually makes sense with the population-wide studies that showed Americans to be at an 18% increased risk of cancer with meat consumption –without breaking it down by genetic differences.  I think this is a great example of why dietary recommendations based on population-wide studies are often only applicable to a portion of the population.

For those of you who want to get geeky with the genetics, here is a description from the study on the function of the GATA3 gene:

GATA3 has long been associated with T cell development, specifically Th2 cell differentiation [25]. GATA3 is up-regulated in ulcerative colitis [26], which is associated with increased risk of colorectal cancer [27]. However, the role of GATA genes as transcription factors extends to epithelial structures with a known role in breast, prostate and other cancers [28]–[30]. GATA factors are involved in cellular maturation with proliferation arrest and cell survival. Loss of GATA genes or silencing of expression have been described for breast, colorectal and lung cancers [30].

Finally, just for all the Parks and Recs fans who always think of Ron Swanson when they hear the word ‘meat’:




Weight Loss: Optimizing your diet based on your genes

Diet gurus, talking heads on TV, government food pyramids, and your friend who lost 20 pounds…

What do they all have in common?  They all know the perfect diet that will whip you into shape and make you feel good.

If that diet doesn’t work for you?  Well, you must have been cheating. You didn’t eat clean enough.  You didn’t stick it out through the ‘keto flu’ long enough….

It must be all your fault that you are failing on their perfect diet.
Or is it?  We all accept and embrace our differences when it comes to skin color, hair color, etc — different phenotypes based on our gene expression.  It is time for everyone to realize that we are all different when it comes to diet and weight loss as well.

Table of Contents:
The Very Basics
Circadian Foundation
Matching your genes to current diet trends
Genes Related to Weight Gain
The Gut Microbiome Influences Weight
Final Thoughts

The Very Basics

I’m assuming that most people reading this already have the basics in place:  eating healthy food, organic when possible, and not smoking or drinking alcohol in excess.  If you are eating a PopTart for breakfast and washing it down with Mountain Dew, well…    back up and start off by getting rid of the processed junk food.

Why get rid of junk food?  I think most of us have a sense that the preservatives, additives, colorings, and unrecognizable words on the ingredients list are probably not all that healthy. One thing that you may not have considered, though, is the impact of emulsifiers and surfactants in foods. Recent studies have looked at the effects of some substances, such as cellulose and polysorbate 80, which are used as emulsifiers to change the texture of foods. They found that these food additives, which are considered safe by the FDA, change the mucosal barrier in the intestines, allowing bacteria closer contact with the surface of our intestinal cells, leading to irritation/ inflammation. This leads to weight gain without increased food intake, and for some, an increased risk of IBD.  Read through the following article to check to see if your genes put you at a higher risk for having problems with emulsifiers in foods:  Microbiome Microbiome + Genetics + Emulsifiers = Obesity

Building the platform for good health
Most people want to lose weight to ‘get healthy’. We are inundated with stories on the horrible health consequences of being overweight, accompanied by photos of protruding bellies and people eating giant burgers. Being overweight causes cancer, diabetes, heart attacks… and well, it is just generally loathed because fat people are smelly slobs with no common sense or self-control. Right? Well, maybe not. For example, read up on the ‘obesity paradox’, where large studies (~250,000 people) have shown that mortality rates are lower for those who are overweight. It is a U shaped curve for mortality after heart attacks, where those who are overweight are least likely to die and those who are underweight or morbidly obese being at the highest risk for death.[study]

Perhaps we are all looking at weight loss backward. Instead of losing weight to get healthy, we should get healthy and then naturally lose weight. We can look at being overweight or obese as a symptom of the wrong diet and lifestyle for our genes, with finding our own genetically correct diet and lifestyle as the way to get to get healthy first.

Circadian Foundation

Fundamental to health for everyone is good sleep and a healthy circadian rhythm.

Don’t stop reading here! Even if you are thinking, “I sleep ok”, please read on.

Circadian rhythms — biological activities tied to the 24-hour cycle of light and dark — are something that we all recognize in animals and plants. We all know that there are nocturnal animals and insects, and we’ve all seen the cool time-lapse videos of flowers opening in the day and closing at night. But somehow it seems to escape us that circadian rhythms, fundamental to all life forms, apply to humans. They are foundational to our biology and our health.

Thomas Edison invented the lightbulb in the late 1800’s, and cities began lighting up at night just over 100 years ago. Prior to that, humans only had light from fire (candle, oil lamps) in the evenings, which emit a yellow/red shifted light. More recently, color TV’s came into everyone’s living room by the ’80s, computers in the ’90s, and then we all got laptops, smartphones, and tablets in the 2000’s. Edison’s incandescent bulb, with its warm yellow light, went by the wayside with the introduction of the CFL bulb and subsequent leap to LED bulbs.

Light at night disrupts our circadian rhythm, which makes sense when you think about it. But the bigger problem came with the TV, computer, cell phones, and CFL/LED bulbs. They all produce a lot of light in the shorter, blue wavelengths (~480 nm), which is the wavelength that signals through receptors in our retina to set our circadian clocks. For the thousands of years before electricity, our bodies’ exposure to blue wavelengths came each day when the sun came up in the morning. Now blue wavelengths are inundating us late into the night, making our body think that it is still mornings.

Before anything else for our health, we need strong circadian rhythms with melatonin onset in the evening when the sun goes down and sunlight hitting our eye in the morning as the sun comes back up.

There is a ton of research coming out about the health effects of messing with our circadian rhythm, and the Nobel Prize was just given for the discovery of the circadian clock genes.

Why am I going on and on about this for a weight loss article? Studies show that low levels of light at night (like from a night light or street lights shining through the window) cause mice to gain fat compared to mice eating the exact same amount of calories but with dark at night. Weight gain due to light at night is backed up by many studies of people working late shifts. Other circadian rhythm disruption consequences include increased risks of cancers, heart disease, and diabetes (yep, same health risk list as above for obesity).

Genetically, some of us are more sensitive to disruptions of circadian rhythms and melatonin production than others. Some people are a double the risk of diabetes from a melatonin receptor variant, and that risk can be mitigated through the timing of meals and, perhaps, blocking blue light at night. Read through my Melatonin and Circadian Rhythms articles to check your genes for higher susceptibility to circadian disruption: Color TV has made us fat: Melatonin, Genetics, and Light at Night and Circadian Rhythms: Genes at the Core of Our Internal Clocks

Even if you aren’t at a higher risk genetically, blocking blue light in the evening with blue-blocking glasses will benefit everyone from a health standpoint. From all the research studies that I’ve read, the biggest thing that we can do for our health (other than not smoking or excess alcohol) is to get our circadian rhythms on track by blocking blue light for two or three hours before bed, sleeping in the dark, and getting outside in the morning to see the sun.

Matching Your Genes to Current Diet Trends:

If you are looking at current diet trends to give you some ‘rules’ to follow, you may be reading up on Paleo, ketogenic, intermittent fasting, Mediterranean, vegan, juice fasts, and detox cleanses.

How do your genes play a role in which diet to choose? Well, they actually may play more of a role in which diet to eliminate…

Saturated fat consumption is tied to increased risk of heart disease for people with certain genetic variants. So a diet high in saturated fat, such as Paleo or keto, might not be a great long-term solution for some people depending on their genes. Read Saturated Fat and Your Genes and check your genetic data to see if you are at risk.

Fasting or a ketogenic diet is counter-indicated for people carrying genetic mutations that decrease their ability to burn fatty acids for energy. Check out Short Chain Acyl-CoA Dehydrogenase Deficiency and Medium Chain Acyl-CoA Dehydrogenase Deficiency to see if you carry one of those mutations.

Some people are genetically better at breaking down carbs than others. Amylase is the enzyme your body produces to break down starches, and we vary genetically in the amount of amylase that we produce. Read through Digesting Carbohydrates: Amylase Variants to determine if you are a high or low amylase producer. This plays more of a role in whether you are likely to regain weight rather than in initial weight loss.

Carbohydrates play a role in blood glucose levels as well, and this is modified by your genetic variants. A Paleo diet which is low in carbohydrates may work well for someone who has a higher insulin reaction to carbs. Check out your likely reaction to carbs in Carbohydrate metabolism: Your genes play a role in insulin and blood glucose levels

When you eat may be more important than what you eat. If you are considering Intermittent Fasting (or really, any diet), you should check on your melatonin receptor genetic variants. Melatonin interacts with insulin release and overnight blood glucose levels, and some people are at a higher risk of diabetes if they eat later in the evening. Read Color TV has made us fat: melatonin, genetics, and light at night.

Clean eating may be a key for those who have problems with detoxifying endocrine disruptors, which can lead to weight gain. Check out BPA: Genetics and Detoxification and Detoxifying Phthalates: Genes and Diet.

Genes related to weight gain

There isn’t one smoking gun ‘fat gene’ that makes people gain weight, with a few rare exceptions. But there are a lot of minor players in the field of genetics and obesity. Quite a few different genes have been found to correlate to an increase in BMI of say a half to one or two points. Knowing how you are genetically predisposed to weighing a little more may help you find a diet that works for you.

FTO genetic variants have been linked in many studies to an increased risk of obesity. Check your FTO variants and read about the possible lifestyle and diet solutions.

MC4R is a gene involved in regulation of appetite and metabolism. Variants in the gene have been linked to a higher risk of obesity and metabolic dysfunction.  Read more and check your genetic variants in the article Obesity Genes: MC4R.

Our cannabinoid receptors are involved in more than just getting high on cannabis.  Some people have more active cannabis receptors which have been linked to increased appetite and weight gain.  I think of it as a minor case of the munchies.  Check your cannabinoid receptors: Cannabinoid receptors, metabolism, inflammation, and obesity.

The Gut Microbiome Influence Weight

There have been several studies showing the influence of the gut microbiome on weight. The most intriguing studies have shown that transplanting the fecal microbiome from an obese mouse to a normal weight mouse will make the normal mouse become obese.

How can you know if your gut microbiome is to blame? You could do a test through a service like uBiome. They can tell you how your microbiome compares to other people’s samples, but they can’t give you a miracle probiotic pill to change anything.

Your genes also play a role in your gut microbiome, influencing which bacteria are likely to thrive there. Bifidobacteria strains have been associated with a reduced risk for obesity.
Read more: How our genes shape our gut microbiome and our weight

Final Thoughts

For almost all of us, gaining too much weight isn’t something that has just one cause. Thus, losing weight may need multiple solutions applied together.  Focusing first on health may bring about the weight changes naturally.

Getting the foundation down through blocking blue light in the evening, thus increasing melatonin synthesis and regulating circadian rhythm, will help with many aspects of health including weight loss.

Prioritize the rest — whether to remove toxins, go on a ketogenic diet, or try intermittent fasting — based on your genetics.

Finally, ensure that your gut microbiome is healthy and not adding to your weight problems.

Salt and High Blood pressure: Genes Make a Difference (Patrons only)

Salt: Is it good for you? Or is it putting you at risk of high blood pressure?

There is an interesting new book out by Dr. James DiNicolantonio called The Salt Fix that makes the argument that the experts got it wrong as far as the salt and blood pressure connection goes.  In contrast, the American Heart Association tells us that our sodium intake causes our high blood pressure.  Either argument could be valid, depending on your genetics.

A recent study found that approximately 25% of people with mild hypertension had their blood pressure increase on a low sodium diet.    And a 2015 review fount that salt sensitivity for blood pressure is “estimated to be present in 51% of the hypertensive and 26% of the normotensive populations”.

Disclaimer timeout:
Everything written here is just for informational purposes. While some of the genetic variants that make a difference in salt intake are presented here, there are more variants that aren’t covered by 23andMe or Ancestry data and are not discussed here.

Back to the topic at hand…
In the US, the FDA recommends 2,300 mg of sodium per day, which is about 6 g of salt.  The CDC’s sodium fact sheet claims that the average salt consumption is the US is around 3,400mg/day and recommends that everyone should cut back on sodium.

One thing to note when looking at studies on salt consumption is that many studies have different definitions of low-salt vs. high-salt depending on what is normally consumed for that population.

Quick Recap:
Some are sensitive to salt; it makes their blood pressure increase.
Some are insensitive to salt; it has no impact on blood pressure.
Some have blood pressure rise with a low salt diet.

Genetic variants for salt-sensitive blood pressure:

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Why Allegra may not work as well for you: genetics of ABCB1 proteins (Patrons only)

Ever wonder why a certain medication may work great for a friend and do nothing for you?  One reason could be your genes.

Let’s take fexofenadine (Allegra) for example.  You have watery eyes and a drippy nose during spring allergy season and pop an Allegra.  There is a lot that goes on in your body before that medication brings about allergy relief.  It has to dissolve, be absorbed, get transported to the cells where it is going to act — and it has to stay inside of those target cells.

Staying inside the cells instead of the medicine being transported back out again is where genetics comes in to play.

Some medications and other toxins are transported back out of cells by an ATP-binding cassette transporter protein encoded by the ABCB1 gene.  In the epithelial cells that line your intestines, the ABCB1 proteins are involved in pumping substances back into the intestinal lumen.  So imagine if you take an Allegra, it dissolves, gets absorbed, and then part of that gets pumped back into the intestines to be eliminated. Genetic variants in ABCB1 affect how much stays in the cells vs getting eliminated (through intestines, bile, urine).

In general, it seems like a good thing for the body to get rid of a substance that it thinks might be toxic. While an allergy medication not working quite as well is not that big of a deal, the real problem comes in when trying to keep chemotherapy drugs inside of cancer cells in order to act upon them.  This gene has been studied in depth for cancer treatment drugs.

ABCB1 gene (multidrug resistance protein, p-glycoprotein):

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Biohacks – Experiments and Optimizations Based on My Genetics

After three years of digging into genetics and learning all that I can about my genes, I wanted to get a little personal and share a few things that have worked for me.

I would also love to hear back from all of you.  Leave a comment below or comment on the Facebook page if you have learned something from your genes and what impact it has had on your diet or lifestyle.

n=1 experiments:  the best lab rat is me

Methylation cycle:
I started off my genetic ‘lifehacking’ the same way that many people do: “Oh, no! I have an MTHFR polymorphism that affects so many things”.  So, of course, I read a few things by people with the word doctor next to their names and then ran out and bought some methylfolate and some hydroxycobalamin (B12).  Methylfolate, at a 400 mcg dose, was the first vitamin or supplement that ever had an effect on me: it gave me an almost immediate headache! I was fascinated by the idea that a vitamin could do something- even something bad – that quickly.

Backing off the methylfolate for a while and then re-introducing it slowly at less than 100 mcg/day got me around the headaches and gave me a new appreciation for ‘just a vitamin’.  A 400 mcg capsule is tiny and taking it apart to sprinkle out a quarter of it a day seemed like it would be impossible to affect me, but it did.

So what did adding methyl folate and hydroxocobalamin do?  It was subtle, but I found that I was no longer as foggy headed, no longer searching for words, and had more energy in the afternoons.  I was in my early forties, and I no longer had that horrible feeling that I was ‘getting old’!

What have I learned since then?  Having read a lot more from other researchers and medical doctors, I’ve come to realize that for me, creatine, glycine, and choline are bigger players in my mental fluidity and energy levels, rather than methylfolate.  I do still take 400 mcg of methylfolate periodically, but I tend to do that just when I haven’t been eating a lot of folate-rich foods.   (Want to learn more about the role of creatine and glycine in the methylation cycle?  Chris Masterjohn has an excellent podcast on the methylation system, with a transcript available if you would rather read than listen. )

Quick recap and links:
MTHFR and other methylation cycle genetic variants.
Low doses of methylfolate and hydroxocobalamin were a good start.
Optimized with increasing glycine, creatine, and choline consumption.


Histamine intolerance:
In looking into my methylation cycle genes, I came across some research on the genes that produce the DAO enzyme that breaks down histamine in the intestines.  Realizing that I had a couple of variants there that caused a decreased production of the DAO enzyme, I started looking into the implications of what that meant, which lead me to information on histamine intolerance.

Lightbulbs went off!  My permanently stuffy nose, constant throat clearing, migraines, heartburn, and periodic itchy hives all suddenly made sense.  I had had allergy testing about ten years earlier because I had noticed that allergy medicine reduced the frequency of hives for me.  But the doctor told me that I was only mildly allergic to a couple of types of tree pollen and that allergy medicine couldn’t be helping my migraines.  Turns out that I shouldn’t always listen to the doctor without questioning…   A low histamine diet gave me immediate results.  I could breathe through my nose, got rid of the post-nasal drip, migraines were gone, and nothing itched.  I haven’t needed to stay on a low histamine diet long term, but I do still stay away from eating a lot of high histamine foods in one meal.

While my genetic predisposition to produce less DAO was playing a role in my histamine issues, I knew that it wasn’t the root cause.  Those polymorphisms in the gene that produces DAO are fairly common and everyone with them doesn’t have histamine intolerance.  I think for me, the problem was based in my gut microbiome.  I had been doing all the ‘healthy stuff’: drinking kombucha, taking probiotics, fermenting my own sauerkraut, and making homemade yogurt.  Cutting out all the ferments helped my histamine problems.  Getting my microbiome tested and finding out that I had no bifidobacteria lead me to find a probiotic that was not full of histamine producing strains.  Adding gelatin to my morning coffee increased my glycine intake, probably helping my gut lining. Eating dinner earlier, sleeping better — everything probably plays a part.

Quick recap and links:
Histamine related genes.
Low histamine diet, microbiome testing, the right probiotics, good sleep, glycine, etc.


I’ve always thought of myself as an ‘ok’ sleeper.  I usually could fall asleep easily and wake up at a decent time.  Yes, I had the occasional (and sometimes more frequent) bouts of being wide awake from 3 am – 5 am, but I didn’t think that sleep was something that I needed to focus on.

After reading a few studies on low levels of light impacting sleep quality, I took the plunge (ok – it ended up costing less than $100) and bought some light blocking curtains for my bedroom.  It really did make a difference in how well I slept.  Fast-forward a year…  I did more and more reading on the effects of blue-light at night, realized the research was solid and pretty definitive, and finally spent ten bucks on a pair of blue-blocking safety glasses.  I wear them every evening now for a couple of hours before going to bed.  It took a couple of weeks to notice a difference, but it hit me one day that I was sleeping like a log and jumping out of bed in the morning, wide-eyed, bushy-tailed and all the other cliches.

I’ve been wearing the dorky looking glasses now for about six weeks.  Yep, my husband and kids still laugh when I put them on.  But I feel really good each morning, and I haven’t seen 3 am in six weeks.  I have noticed that I am sleeping about a half hour less than I used to sleep.

Quick recap and links:
Melatonin is pivotal in setting circadian clock genes. Wearing blue-blocking glasses in the evening makes you look dorky, but it is worth it for great sleep and increased morning alertness.


I had tried the ketogenic diet years ago (the Adkins diet) and felt truly awful on it.  With all the great studies coming out about intermittent fasting, I couldn’t figure out why it didn’t make me feel great to skip breakfast.  Figuring out that I carry a mutation for short-chain acyl-CoA dehydrogenase deficiency made sense of all of it.  I have a somewhat impaired ability to burn fat for energy, so a ketogenic diet or fasting makes me feel icky. While I think the science coming out about intermittent fasting is extremely interesting, it is good to know why eating breakfast works for me.  I have shifted dinner to be a little earlier, giving me a 12-13 hour fast overnight.

Quick recap and links:
SCADD and MCADD are two inborn errors of metabolism that may make it more difficult to rely on burning fatty acids for energy.  Eat some carbs and don’t fast for too long.


Vitamin A:
After looking into my genes that convert beta-carotene to vitamin A, I realized that I wasn’t coming anywhere near the RDA for vitamin A and probably never had.  So I got a vitamin A supplement that was truly vitamin A and not beta-carotene, and I took it off and on for several months.  No mental boost, no feeling great, nothing.  Except, one day I noticed the back of my arms were smooth.  I had had little bumps on my arms – keratosis pilaris – since I was a kid, and now they were completely gone.  It hit me then that if vitamin A helps acne, that it may also help keratosis pilaris.  A little research showed that was true, and I had probably been slightly deficient in vitamin A my whole life.  Since Vitamin A is a fat soluble vitamin, I didn’t want to go overboard on supplementing with it.  So I’ve taken a few months off of supplementing it several times over the past couple of years, and after a month or two of no vitamin A pills, my keratosis pilaris starts coming back.   (Yes, I know that eating liver could be a better option than vitamin A pills, but I really hate liver.)

Quick recap and links:
Vitamin A conversion genes.  Adding in vitamin K took away keratosis pilaris.
Supplement of Vitamin A (retinyl palmitate).  Don’t go overboard on Vitamin A supplements since they can build up.


I mentioned above that choline plays a role in the methylation cycle.  Earlier this spring, I came across some interesting research on how people’s need for choline varied quite a bit, depending on their genetics.  I wrote a blog post on it, noted that I was in the camp of needing more choline, and made more of an effort to eat eggs several times a week for breakfast.  Recently, I read back through my own article on choline and it finally hit me that even if I ate a couple of eggs every day (and I wasn’t that consistent), it wasn’t going to get me to the level of choline that I needed.  So I finally took my own advice :-) Supplementing with a little bit of choline bitartrate gives me a nice mental boost and extra energy.  Too much, and it gives me a headache, reminiscent of the headaches that methylfolate initially gave me. This time I’m taking it slow and not going overboard with it, and I’ve got some Alpha-GPC choline ordered to see if it is a better fit for me. (Yes, I know that liver is a great source of choline as well, but…)

Quick recap and links:
Choline genetic variants.
If you don’t get enough via diet, choline bitartrate or alpha-GPC may be worth a try.


We are all different:
Yes, I get the irony of writing a long blog post all about myself and concluding that ‘we are all different’.  But truly, the biggest thing that I’ve learned from all my reading on genetics is that we really are all different.

What works for me may not work for you, even if you have some of the same genetic variants that I do.  Learn to listen to your own body and not what an article tells you to do.

General, population-wide nutritional advice may work for the majority of people, but on an individual level, it often misses the mark.   Read, learn, and figure out what works for you.

Intriguing Genes: Do you taste what I taste?

Ever wonder why some people don’t like Brussel sprouts or strong, dark coffee?  I love a good, dark roast, cup of coffee, and Brussel sprouts and cabbage taste great.  It turns out that I can’t taste the bitter compound in them, but the majority of people can. On the other hand, I have yet to find a brand of stevia that I like because of the awful aftertaste. It turns out that I am genetically more sensitive to the bitter taste of steviol.

If you are old enough, you probably remember the Life cereal commercials with Mikey, where the ultimate, picky taste test is whether “Mikey likes it!”  So why is it an advantage to have differences in our taste receptors?  Having part of the population able to taste a bitter toxin and warn of the danger is vital, while also having others who scarf down Brussels sprouts lets the community as a whole know that a bitter, but healthy, food is good to eat.

Taste buds on the tongue. By OpenStax – Wikimedia Commons.

Here’s a science-y example: One of the substances that some people can detect, at extremely low concentrations, is aristolochic acid, a toxin found in certain plant seeds.  In Eastern Europe, the plant tends to grow as a weed in fields, contaminating crops and causing kidney disease in those who ate the toxin. There is a 50-fold difference in people’s ability to taste aristolochic acid, although researchers are still trying to untangle the effects of taste ability vs the effect of the sensitivity of the gastrointestinal receptors on the disease-causing aspects of the toxin.

We all know that we taste food in our mouth, but it turns out that these same receptors are also found in the gastrointestinal tract, in the airways, and in the urinary tract. New studies are coming out all the time on the various functions that these ‘taste’ receptors perform in the body.[study][study]

Genes involved: 
TheTAS2R gene family, containing 43 different genes, is responsible for various bitter taste receptors, while the TAS1R family (just two genes) is responsible for sweet and umami tastes.  Salty and sour taste receptors are still being sorted out, and it turns out we also have taste receptors for fat.

Bitter taste receptors:
TAS2R38 gene:
Linked to the taste of bitter in broccoli, Brussels sprouts, cabbage, watercress, chard, ethanol, and PROP. [ref][study]  Interestingly, this taste receptor is also being studied as a target for type 2 diabetes medicines and is involved in triggering the production of bile acids.

Check your 23andMe results for rs713598 (v.4 and v.5):
GG: Can taste bitter in broccoli, etc.
CG: Probably can taste bitter
CC: Probably unable to taste some bitter flavors
Check your 23andMe results for rs10246939 (v.4 and v.5):
CC: Can taste bitter in broccoli, etc.
CT: Probably can taste bitter
TT: Probably unable to taste some bitter flavors


TAS2R16 gene:
Associated with the taste of beta-glycorpyranoside [clinvar], which is in ethanol, bearberry, bacteria in spoilt or fermented foods, and willow bark (salicin).  [study]  There have been studies looking into the link between TAS2R16 gene variants and colon cancer, pursuing the idea that either a variation in vegetable intake would affect cancer risk or a variation in the amount of natural salicin compounds eaten would affect colon cancer risk (aspirin being preventative in colon cancer for some). The studies done so far though haven’t been able to make that connection. [study]

Check your 23andMe results for rs846672 (v.4 and v.5):
CC: Can taste bitter in ethanol, fermented foods, etc
AC: Probably can taste bitter
AA: Probably unable to taste some bitter flavors
Check your 23andMe results for rs846664 (v.5 only):
AA: Can taste bitter in ethanol, fermented foods, etc
AC: Probably can taste bitter
CC: less able to taste some bitter flavors
Check your 23andMe results for rs978739 (v.4 and v.5 only):
TT: Can taste bitter in ethanol, fermented foods, etc
CT: Probably can taste bitter
CC: less able to taste some bitter flavors


TAS2R19 gene:
Linked to the taste of quinine,  the bitter taste of grapefruit and tonic water. [study]

Check your 23andMe results for rs10772420 (v.5 only):
AA: Can taste bitter in quinine
AG: Probably can taste bitter in quinine
GG: Less able to taste bitter in quinine

TAS2R14 gene
Stevia taste receptor — as well as absinthe, aristolochic acid, fishberries, and Hoodia Gordonii.[study] [ref]  There is a polymorphism (rs2234001, covered by AncestryDNA but not 23andMe) that causes some people to detect stevia as bitter, some as only sweet, and some as sweet with a bitter aftertaste.  You don’t really need a genetic test for this one, though, since you can just taste some stevia and know whether you think it is sweet or bitter or both.

Of those who can taste bitter, some have a much strong perception of the bitter taste based on the rs3741843 variant. [study]

Check your 23andMe results for rs3741843 (v.4 only):
TT: Lower sensitivitity to bitter taste from stevia.
CT: Stevia tastes more bitter (if able to taste the bitter)
CC: Stevia tastes more bitter (if able to taste the bitter)

Sweet and Umami Taste Receptors:

Sweet taste receptor for which variations are estimated to produce about a 16% difference in variability of sweet taste perception.  This receptor also plays a role in umami taste as well, along with another gene. [ref] A study found an increase in kid’s cavities linked to those who have a decreased sensitivity to the taste of sugar, perhaps due to eating more sugar to reach the same perception as those without the variant.  Scientists are still sorting out the reason why and how the change in the taste receptor protein is also altering insulin secretion.  [study]

Check your 23andMe results for rs35744813 (v.4 only):
TT: Decreased taste sensitivity for sucrose
CT: Somewhat decreased taste sensitivity for sucrose
CC: Normal taste receptor for sucrose
Check your 23andMe results for rs307355 (v.5 only):
TT: Decreased taste sensitivity for sucrose
CT: Somewhat decreased taste
CC: Normal taste sensitivity for sucrose


More to read:
Here are a few more studies that are digging into the roles that our taste receptors play –outside of just the taste we perceive in our mouth.  Read through them to find out the more about the interactions of leptin, endocannabinoids, and insulin with taste receptors.  Pretty cool stuff!

Lactose Intolerance: The genetics of not producing lactase

Are you a milk drinker? Does pouring a cold glass of milk sounds good? Your genes control whether you are likely to produce lactase as an adult, and it is easy to check your 23andMe or other genetic data to see if you are likely to enjoy a big glass of milk.

Personally, I had always thought it a bit strange that my husband likes to drink a glass of milk with dinner. It just didn’t appeal to me — at all. I didn’t think ever think about lactose intolerance, though, because I still drink small amounts of milk in my coffee and on cereal. Turns out that I am one of those people who doesn’t produce lactase as an adult. I am relying on bacteria in my gut to break down lactose, so I don’t go overboard on drinking milk.

Getting into the science:
Lactose, a sugar in milk, is broken down by the enzyme lactase which our bodies produce in the small intestines. For some people, the production of the lactase enzyme stops when they become an adult, driven by a genetic variation near the LCT gene. This means that some adults are genetically predisposed to not be able to digest larger quantities of milk.

The percentage of the population with the genetic variations differs quite a bit among people with different backgrounds. Producing lactase as an adult is the most common genotype for Caucasian populations, while in Asian populations, the majority do not produce lactase as an adult. This is thought to be an adaptation by Caucasian populations in Europe who relied on dairy products as a source of protein.

For Caucasians, the main variant to look at is located in the MCM6 gene, which influences the LCT gene.  Approximately 90% of Caucasians will have AA or AG and still produce lactase to break down milk as an adult. In Asian populations, less than one percent will carry the G allele.

Bacteria in the gut also break down lactose, so even those who don’t produce lactase can often handle digesting limited amounts of milk.

Genes Involved in Lactose Production

If your genotype is GG on rs4988235, you will not produce lactase and will probably not be able to handle larger quantities of milk as an adult. From talking with other people about this, it seems that those with GG naturally limit their intake of milk.

Check your 23andMe results for rs4988235 (v.4, v.5 of 23andMe; AncestryDNA):
AA: Still produces lactase as an adult
AG: Still produces lactase as an adult (probably less than those with AA – study)
GG: No longer produces lactase as an adult

Interestingly, a Dutch study showed that while the GG genotype resulted in adults having a lower dietary calcium intake, that did not correspond to a lower bone density or more fractures.

For people of African origin, a different variant of the MCM6 gene is found in about 10-15% of the population and is associated with being able to produce lactase as an adult.

Check your 23andMe results for rs145946881 (v.4, v.5 of 23andMe; AncestryDNA):
CC: Still produces lactase as an adult [study]
AC: Still produces lactase as an adult
AA: No longer produces lactase as an adult

A very small number of people may also have a rare mutation (not covered by 23andMe or AncestryDNA) that causes the lactase gene not to function at all, even in childhood.


Probiotics to the rescue?

Quite a few studies have looked at the effect of probiotics on lactose intolerance.  One study from May 2016 found that a specific strain of Lactobacillus acidophilus was significantly effective in reducing the symptoms of lactose intolerance.  There are many types of lactobacillus bacteria available as probiotics and in yogurt or other fermented foods.  It is likely that some strains will be much more effective than others in reducing lactose intolerance symptoms for an individual, and it may be worthwhile to try several different types of Lactobacillus probiotics.

If you are interested in digging deeper into the types and numbers of lactose-consuming bacteria in your gut, you could do a microbiome test from uBiome or another company.

More to read:


originally published 2/23/15, updated 10/17

Intriguing Genes: Differences in how we smell things

Learning about genetics has given me a new perspective on so many different subjects.  For example, seeing first-hand how much of a difference the right vitamins and minerals make in a person’s mood due to changes in their neurotransmitter balance has made me much more understanding.  Cut me off in traffic?  Instead of just assuming you are a jerk, I now wonder if you were driving aggressively due to needing a little lithium orotate along with the right type of B12.

One of the things that recently surprised me is that we don’t all smell the same odors.  I knew that some people have a loss of the sense of smell when they get older and that inability to smell could be a marker for some diseases, but I was intrigued by the idea that any two people may have as much as a 30% difference in their functional ability to detect different specific odors.[study]

So now I have to once again change my perspective. Over half the population can’t smell a compound in floral fragrance nearly as well as I can.   Instead of being irritated at that lady wearing too much floral fragrance, now I recognize that she probably thinks it is lightly pleasant — I’m the one that is different.  And now I wonder what it is that I’m not able to smell!

Humans have around 400+ different olfactory receptor proteins that are coded for by our genes.  Only a small portion of these receptors have been mapped to specific odors so far.  (I’m guessing there isn’t a lot of money in researching olfactory receptors vs. curing diseases…)

There are several different genetic variants of odor receptor genes that aren’t covered by 23andMe.  One of them, OR7D4 variant rs5020278, is linked to a persons ability to smell the sex steroid derived odorants, androstenone and androstadienone.  Researchers have studied how the ability to detect androstenone plays a role in whether a person is likely to eat pork from uncastrated male pigs.  Some people perceive the meat as smelling very unfavorable to eat, known as ‘boar taint’.[study] [study] It turns out that the same odor perception variant can also play a role in sociosexual behaviors in women.[study]

Other studies have linked odor receptor variants to increased BMI. One study found that participants who were less sensitive to smelling oleic acid were more likely to eat more nuts, seeds, and nut spreads (high in oleic acid) as well as having a higher BMI.  The study sums up: “fatty acid olfactory sensitivity is clearly linked with fatty acid taste sensitivity albeit acting through separate pathways. Hyposensitivity to fatty acid taste was associated with disinhibited eating behaviour. Furthermore, participants who were hypersensitive to oleic acid taste perception had lower BMI values than those who were hyposensitive.”

So what kind of interesting things can we learn from 23andMe data about what/how we smell odors?

OR5A1 gene:
The variant rs6591536 has been linked to the ability to smell β-ionone. Those who carry an G allele are more able to detect β-ionone, which is a floral smell found in roses, jasmine, violets, and more.  It is a compound often used by fragrance manufacturers for floral smells. [study]

Check your 23andMe results for rs6591536(v.4 and v.5):

  • AA: less able to smell floral (β-ionone)
  • AG: more able to smell floral (β-ionone)
  • GG: more able to smell floral (β-ionone)

OR10A2 gene:
Cilantro is one of those foods that people either seem to love or hate.  Turns out that an olfactory receptor gene variant may play a role in how we perceive it.  [study]

Check your 23andMe results for rs72921001(v.4 and v.5):

  • AA: less likely to think cilantro tastes like soap
  • AC: less likely to think cilantro tastes like soap
  • CC: more likely to think cilantro tastes like soap

Asparagus Pee
Asparagus pee smell….  was something that I assumed everyone smelled.  Turns out that more than half of people in a study of nearly 7000 were unable to smell asparagus pee.  A second study looked into whether it was a lack of ability to smell the odor vs. a lack of producing the odor.   The study found that 8% of participant’s urine did not have a detectable asparagus odor and also that the ability to smell the asparagus pee smell is much stronger in those who carry the A allele of rs4481887.

Check your 23andMe results for rs4481887 (v.4 and v.5):

  • AA: most likely can smell asparagus pee
  • AG: likely can smell asparagus pee
  • GG: least likely to be able to smell asparagus pee

Being able to smell or not smell certain odors has been linked to food preference and a risk of obesity.  For OR7G3, those carrying the C allele variant had almost a whole point higher BMI on average.

Check your 23andMe results for rs10414255 (v.4 and v.5):

  • C allele: linked to more hunger, disinhibition in eating, and higher BMI
  • TT: lower BMI (on average)

Beyond just smelling the flowers….

While this has been a rather light look at being able to smell different odors, there are more serious issues for people with anosmia (inability to smell) and I encourage you to dig deeper into the topic if you have an inability to smell.

It seems that the research into odorant receptors is just in its infancy with quite a bit of new information coming out in the past couple of years.  We actually have these odorant receptors other places than just in our nose, leading to the idea that they play other roles in the body.

“Accumulating molecular evidence indicates that the odorant and taste receptors are widely expressed throughout the body and functional beyond the oronasal cavity – with roles including nutrient sensing, autophagy, muscle regeneration, regulation of gut motility, protective airway reflexes, bronchodilation, and respiratory disease. Given this expanding array of actions, the restricted perception of these GPCRs as mere mediators of smell and taste is outdated.” [study]

HLA typing is also linked to olfactory gene variants.  A recent study looked at using smell tests as a way of determining HLA variants.

One last tidbit for your olfactory knowledge base is that some molecules are transformed in the mucus before reaching the odor receptors.  CYP1A2 genetic variants (check yours here) were found to play a role in the conversion of acetophenone (cherry, almond chicory smell) to methyl salicylate (wintergreen smell) in the nose.[study]  So the whole kit-n-kaboodle gets a little more complicated.

More to read: