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.

How our genes shape our gut microbiome and our weight

Several studies have come out recently showing that those who are overweight have a different gut microbiome composition than those who are lean.  There have also been interesting mouse studies showing that transplanting feces from obese mice into lean mice causes the lean mice to become obese.  A 2010 study that found that supplementation with the probiotic Lactobacillus gasseri SBT2055 decreased abdominal fat and body weight.  The case for our microbes helping to shape our weight is fairly strong.

But why do some people have higher gut microbe populations of certain beneficial species than others?  Genetics!  Along with diet and environment, of course!

I find it fascinating that genetics plays a big role in the types of microbes that can live in our bodies.  Specific genetic variants can promote or discourage microbes in our guts.  For example, a FUT2 polymorphism causes some people to be immune to the Norovirus and the rotavirus (sometimes called the stomach flu).

Here are a few of the genes that play a role in determining which microbes inhabit the gut microbiome:

APOA5
This gene affects plasma lipoprotein levels including triglyceride levels as well as levels of certain gut bacteria.  Several SNPs in this gene have been associated with triglyceride levels and obesity risk.

An April 2016 twin study looked at metabolic syndrome (including weight) and found that rs651821 was associated with metabolic syndrome (MetS).  The study results found that metabolic syndrome was more common in those with the C allele and, for each C allele, there was an average increase in triglycerides of 24.65 mg/dL.  In looking at the gut microbiome, the study found that those with the minor allele (C) had fewer Bifidobacterium regardless of their MetS status.   Bifidobacterium species have been linked (in this study and in others) to lower BMI and better overall health.[ref]

Check your 23andMe results for rs651821:

  • TT: common (wildtype)
  • CT: reduced Bifidobacterium levels, higher triglycerides, and MetS risk
  • CC: reduced Bifidobacterium levels, higher triglycerides, and MetS risk


MYD88

  • A mouse study using mice bred to be deficient in (MyD88 knockout) found that the mice had significantly reduced levels of Lactobacillaceae (Firmicutes), Rikenellaceae (Bacteroidetes),  and Porphoromadaceae (Bacteroidetes) bacteria compared to mice with normal MyD88.  The study was looking at the influence of the microbiome and genetics in type 1 diabetes and is worthwhile to read through if you have T1D.
  • Another study found that MyD88 is important in clearing Listeria monocytogenes infection.  Listeria infections usually come by eating contaminated foods, giving some people a nasty case of food poisoning.  Normally the intestinal mucosa can protect against systemic infection, but MyD88 deficiency increases susceptibility to systemic infection by the pathogen.
  • A recent mouse study found that MyD88 knockout mice had an increased number of bacteria in contact with the epithelial wall of the intestine.  Normally, the intestinal mucosal layers protect the cell wall of the intestines from direct contact with bacteria.
  • Other mouse studies have found that MyD88 knockout mice are more susceptible to tuberculosis.  This has been confirmed in humans with MyD88 polymorphisms as well.

Several MYD88 variants have been found to reduce levels of MYD88 (most are not covered by 23andMe data).  These are just reduced levels, though, not a complete ‘knockout’, so the results of the mouse studies may not be completely applicable.

Check your 23andMe results for rs4988453:

  • CC: common (wildtype)
  • AC: reduced MYD88 (5x risk of tuberculosis)
  • AA: reduced MYD88 (5x risk of tuberculosis) [ref]

 

Check your 23andMe results for i5000725 (rs137853065):

  • TT: common (wildtype)
  • CC: Rare mutation, listed as pathogenic for MYD88 deficiency

 

Check your 23andMe results for i5000726 (rs137853064  ):

  • CC: common (wildtype)
  • TT: Rare mutation, listed as pathogenic for MYD88 deficiency


NOD1

Nucleotide-binding oligomerization domain containing 1 (or NOD1)

Mice deficient in Nod1 have increased susceptibility to H. pylori.  Other studies have shown that NOD1 variants lead to increased risk of inflammatory bowel diseases in some population.  One study concluded, “Taken together, these data may suggest that NOD1 plays a variable role in different populations that could depend upon environmental and dietary factors.” [ref]

Check your 23andMe results for rs2075822 :

  • AA: common (wildtype)
  • AG: increased risk of IBD
  • GG: increased risk of IBD [ref]


TLR4

Toll-like receptor 4 (TLR4) plays an important role in our innate immunity and is especially active against gram-negative bacterial infections. TLR4 variants have been investigated in conjunction with cancer risk, vaccine response, and transplant rejection among other things.

Check your 23andMe results for rs4986790:

  • AA: common (wildtype)
  • GG: increased risk of gram-negative bacterial infection, septic shock[ref] [ref], and metabolic syndrome [ref]

 

Check your 23andMe results for rs10759932:

  • TT: common (wildtype)
  • CC: decreased risk of H. pylori [ref]


SLC39A8

From Genetics Home Reference: “This gene encodes a member of the SLC39 family of solute-carrier genes, which show structural characteristics of zinc transporters. The encoded protein is glycosylated and found in the plasma membrane and mitochondria, and functions in the cellular import of zinc at the onset of inflammation. It is also thought to be the primary transporter of the toxic cation cadmium, which is found in cigarette smoke.”

Check your 23andMe results for rs13107325:

  • CC: common (wildtype)
  • CT: changes in gut microbiome, obesity, and Crohn’s disease risk
  • TT: changes in gut microbiome, obesity, and Crohn’s disease risk [ref]

Lifehacks

Eating prebiotic fiber, such as inulin / FOS may increase your bifidobacteria.[study]

There are probiotics available containing multiple strains of bifidobacteria.

More to read:

A recent study did extensive analysis on the microbes associated with visceral fat, BMI, and other obesity markers.  The study also found several genes correlated with specific bacteria that are associated with obesity.  The SNPs (none of which are included in 23andMe results) were in the FHIT, TDRGI, and ELAVL4 genes.  The full study is open to read and worth checking out.

Genetics and Gum Disease

I read a study last week that piqued my interest in the interplay between genetics and gum disease.  Maybe there is a genetic reason for my tendency towards bleeding gums when the hygienist stabs her probe into them?  I was intrigued to look into other influences on gum disease to see if there is something more or different that I need to be doing.    So here is a quick summary of several genes involved in either periodontitis or gingivitis.

 

TNF-α (Tumor necrosis factor – α)

TNF-α is an inflammatory cytokine involved in the body’s immune response. Like most things in the body, TNF is important to have in the right amounts.  It does play a role in apoptosis in cancer cells in animals, but too much TNF is implicated in inflammatory diseases such as rheumatoid arthritis.  TNF-α is stimulated by bacterial endotoxin (lipopolysaccharides) as well as other pathogens.  It is one of the body’s primary mediators in protection against bacteria and viruses.  But elevated chronic levels of TNF are implicated in a variety of autoimmune diseases.

rs1800629 – According to a meta-analysis released in Nature in January 2016, the minor allele, A, “leads to two- to three-fold higher transcriptional activity of TNF-α upon stimulation with bacterial lipopolysaccharide14,15. Carriage of the rare -308 A allele is associated with significantly greater TNF-α production and transcription. In addition, the A allele has been associated with increased risk for various non-related infectious and inflammatory diseases, including periodontitis.”  [ref]

 

IL1 (Interluekin 1)

Interleukin 1 is another inflammatory cytokine released in response to endotoxins.

Rs1800587  (minor allele is A) and rs1143634 (minor allele is A) were found to double the risk “for subgingival occurrence of Aggregatibacter actinomycetemcomitans” according to a 2011 study. [ref] Here is a paper on “The Importance of Aggregatibacter Actinomycetemcomitans in Etiology of Periodontal Disease“.

 

IL-6

Interleukin 6 is an inflammatory cytokine that is involved in defense against injury or infection.  This is another cytokine that is important in infection but can also become a problem if it is not regulated well by the body.  [read more]

rs1800795 (minor allele is C) The minor allele is associated with being less susceptible to gingivitis and periodontitis, having an OR=0.36. [ref]  and [ref] Those with the C allele produce less IL6 than those with the G allele.

 

Natural options

So if you now know that you are susceptible to gum issues based on your genetics, here are some natural options to explore.  It almost goes without saying (but I’m saying it anyway) that good oral hygiene measures such as brushing your teeth and flossing are always important.

Natural TNF inhibitors include the usual recommendations for inflammation such as quercetin, resveratrol, and turmeric.  Glycine, found in bone broth, was found in a 1999 study to inhibit TNF-α due to endotoxins.  [ref]

There are several essential oils that inhibit aggregatibacter actinomycetemcomitans.  A 2014 study of three oils found that lemongrass was the most effective of the ones they tested. [ref]  If you use essential oils, do a quick search online; there are many other studies out there looking at other oils as well.

I was curious about whether fluoride in toothpaste would increase TNF.  The only study that I found is a mouse study from the journal Biosciences Biotechnology Research Asia, April 2014.  It shows that serum TNF-α does increase in response to sodium fluoride, but that curcumin and selenium can mitigate part of that elevation.  Read the study for yourself and see what you think… [ref]

 

 

Gut Health and Your Genes – FUT2 Genetic Variants

I am constantly amazed at the interaction between our bodies and the microbes within us.  Yes, a bit geeky, but this stuff is really cool!

Check your 23andMe results to see if you carry the FUT2 gene variant that indicates that you might want to try a bifidobacteria probiotic.

Whether or not you secrete your blood type plays a big role in the type of bacteria that dwell in our gut microbiome and whether you are likely to get sick from the norovirus.  A genetic variant in the FUT2 gene controls whether or not you secrete your blood type.

What does this have to do with our microbiome?  Bifidobacteria, a major genus of bacteria that are found in the colon, are thought to be one of the good guys when it comes to your gut microbiome.  They are lactic acid and acetic acid producing bacteria, and they help the immune system keep everything in check.  These bacteria are involved in breaking down carbohydrates (specifically, oligosaccharides) from the diet and also eat oligosaccharides produced by our body in the intestinal mucosa.[ref][ref]

Oligosaccharides are a carbohydrate that consists of three to nine monosaccharides (simple sugars). There are three types of oligosaccharides that are in the news these days as helpful prebiotics: fructooligosaccharides (FOS), galactooligosaccharides (GOS), and inulin. You can get oligosaccharides as pre-biotic supplements and they are also found in foods like leeks, Jerusalem artichokes, onions, chicory root, and oats.

ABO Blood Group Diagram. Wikimedia Commons - Public Domain.
ABO Blood Group Diagram. Wikimedia Commons – Public Domain.

The FUT2 gene encodes the enzyme fucosyltransferase, which plays a role in forming oligosaccharides. Most people are familiar with the ABO blood type system and probably learned in high school biology about the A antigens and B antigens. But what you may not know is that the antigens (A and B) are sugar molecules on the outside of the blood cell. The FUT2 gene comes into play when looking at the secretion of the blood type in bodily fluids such as saliva and intestinal mucosa.

The oligosaccharides secreted in the intestinal mucosa feed your intestinal flora, but not everyone secretes their blood type. In fact, about 20% of Caucasians are thought to be non-secretors. A FUT2 non-secretor has a homozygous mutation in the SNP rs601338 that changes G to A. Those with AG or GG (heterozygous and wild-type) are FUT2 secretors.

Check your 23andMe results for rs601338:

  •  GG: FUT2 secretor
  •  AG:  FUT2 secretor
  •  AA:  FUT2 non-secretor, lower amounts of bifidobacteria, resistant to norovirus

So what is the big deal about being a non-secretor?  Well, it comes back to our bodies interactions with the microbiome.  In a 2011 study, individuals with the AA allele on rs601338 (non-secretors) were shown to have significantly lower amounts of bifidobacteria in their gut microbiome. This makes sense when you think about bifidobacteria being fed, in part, by our intestinal mucosa.   Interestingly, the same study showed that non-secretors actually had a higher diversity of bacteria.  Another study in 2014 confirms those findings.

An infants microbiome is, in part, colonized from the mother, and bifidobacteria usually make up a large portion of an infant’s microbiome. Breastmilk contains oligosaccharides that feed the baby’s microbiome.

The effects on non-secretor status can also influence breastfed babies of non-secretor mothers. A 2015 study found that “Infants fed by non-secretor mothers are delayed in the establishment of a bifidobacteria-laden microbiota. This delay may be due to difficulties in the infant acquiring a species of bifidobacteria able to consume the specific milk oligosaccharides delivered by the mother.”[ref]

Non-secretor status plays a role in infectious diseases as well.  Both the norovirus (famous for spreading rapidly on cruise ships and through nursing homes) and the rotavirus are much less likely to infect a non-secretor.[ref][ref]  Children who are non-secretors are less likely to have diarrheal diseases.[ref]  H. pylori colonization is also less in non-secretors.[ref]

Secretor status also plays a role in non-infectious diseases as well, possibly through interactions with the gut microbiome. Non-secretors have a higher risk of Type 1 diabetes[ref], alcohol-induced pancreatitis[ref], Crohn’s disease[ref], and adverse outcomes in premature infants[ref].

This is one genetic mutation that is dependent on ancestry and applies mainly to Caucasians. The rs601338 mutation for non-secretors is not found in Japanese populations, but another SNP codes for non-secretors for Japanese, rs1047781 – TT genotype.


Lifehacks

Probiotics containing bifidobacteria:
Several places on the internet mention that bifidobacteria-containing probiotics are good for non-secretors. RenewLife’s Ultimate Flora has a high count of several types of bifidobacteria.   VSL #3 is another probiotic that has good reviews and contains bifidobacteria.

Microbiome sequencing:
If you want to know how many and what type of bifidobacteria are in your gut, you could do a microbiome sample from uBiome or American Gut.  Do read their privacy policies thoroughly before buying.

More to read: