I’m a firm proponent of understanding how people are different. When I first realized that lectins were the issue in plant foods, I assumed that I couldn’t assume people are sensitive to lectins simply because I am. But after helping hundreds of people, I started to see patterns which allow me to determine who is and isn’t lectin sensitive – and more importantly to what degree people are lectin sensitive.
Note that I often say lectin sensitivity and food sensitivity interchangeably. The new SelfHacked Lectin Avoidance Diet cookbook goes into more details about this as well as how to know if you are sensitive to lectins or other substances.
It’s been about two years since my theory of lectins as being a significant cause of issues stemming from food. The theory started out by self-experimentation with foods and then seeing patterns. Foods with more lectins caused more problems.
I then set out to see who else discovered this and found some scattered info here and there but almost nothing seriously studied. I found the only clinical trial available done by Dr. Steven Gundry. The study wasn’t published because Dr. Gundry says he simply lacks time, but I was able to interview him for my podcast.
If I could’ve read this information ten years ago, it would’ve helped me out so much. The problem was that I was too skeptical about listening to others – and for good reason.
I’m the type of person who will be skeptical about ideas such as lectin sensitivity unless I understand concretely why someone like me is lectin sensitive, while someone else can seemingly eat lectins without any significant problems.
At the very least, I’d need to see clear distinctions between myself and others that are objective, rather than listening to someone say that legumes are horrible for everyone (even if that is right).
This post is meant for the skeptics who will rightfully ask: How do I know if I’m lectin sensitive? Why is it other people don’t seemingly have issues? Which biomarkers are important to indicate that you are more lectin sensitive?
The Lectin Sensitive Spectrum
Lectin sensitivity is on a spectrum. Some people are extremely sensitive, such as myself, while others are not significantly sensitive.
This post is my current thinking on how to know if you’re lectin sensitive and how to figure out where you lie on the lectin sensitivity spectrum.
This post combines information from myself, my research and patterns observed from clients over time. I would never have been able to figure these things out without seeing consistent patterns from my clients – so this post is devoted to them.
The vast majority of my clients happen to be lectin sensitive, but how lectin sensitive has for a long time been a question mark in my head that I found hard to be precise about.
You can identify lectin sensitivity by a combination of symptoms, blood tests, and genes. The more of these that you have, the surer you can be that you’re lectin sensitive and the more, you’ll be affected by lectins.
I happened to have all of the biomarkers, and unsurprisingly I am extremely lectin sensitive. So knowing this will make you somewhat less skeptical.
In time, I will keep adding additional ways of knowing if you’re lectin sensitive, but so far this is by far the most cutting edge diagnostic method.
Three Classes of People Who Are Lectin Sensitive
Since my theory, I started to look for patterns from my clients on who was and wasn’t lectin sensitive.
Initially, my theory was that I shouldn’t assume that others had the issue simply because I did. But with experience, I started to see patterns emerge.
There are three main classes of people:
- Those whose health issues were significantly started by lectins because of genetic predispositions in combination with heavy lectin consumption (vegans, vegetarians or people who had grown up with a lot of whole grains such as myself). People in this class will have family members with lectin sensitivity – and almost always at least one parent.
- Those who developed lectin sensitivity after a period of acute or chronic stress.
- Those who developed lectin sensitivity after chronic immune activation -either from biotoxins, infections, chronic injury, excess exercise, sleep deprivation, chronic circadian disruption, etc….
Most of the time people will have a mix of these.
So for example, people will often have some genes in combination with a stressful period -as well as latent infections picked up throughout life.
Health issues starting after psychological stress or chronic immune activation are some of the best predictors of lectin sensitivity.
Chronic brain fog is a symptom that an infection or biotoxin is present. But most of the time, people with a chronic infection or biotoxin will automatically increase sensitivity to lectins both directly (via immune activation) and indirectly by chronic sympathetic or fight or flight activation (caused by inflammation).
Risk Factors For Lectin Sensitivity
The biggest risk factors for developing lectin sensitivity are:
- Psychological stress,
- Marathons/Excess exercise,
- A vegan/vegetarian diet – which is lower in Vitamin A and other nutrition and higher in lectins. Retinol is critical for immune tolerance and a high lectin load for a sustained period will create chaos.
- Less sun exposure (UV and infrared are the best ways to shut the immune system down. UVB also helps create vitamin D3, which is necessary for immune tolerance),
- Less consumption of fish (DHA is critical for immune balance),
- Chronic circadian disruptions, which imbalances the gut immune system,
- Infections/Biotoxin exposure,
- Sleep deprivation, which will disturb your immune system.
- Antibiotics, which will disturb your gut flora…
- Possibly EMF exposure – some animal studies show that EMFs increases the nervous system and affect sleep (R). So growing up in a big city with lots of cell and wifi signals…I’m skeptical but open-minded about this.
Why Do These Risk Factors Increase Lectin Sensitivity?
Anything that activates your immune system, and nervous system will increase lectin sensitivity.
So chronic infections will cause both immune activation and an activation of the nervous system. However, in these people, staying away from lectins won’t cure their problems because lectin sensitivity is just a terrible side effect, not the cause.
Various plant lectins also activate TLRs – especially wheat lectins (R).
One possibility is that when a threshold of TLR or immune activation is reached, you start getting more problems from lectins.
Immune activation will also activate your nervous system, which itself has a bunch of negative effects on the gut.
Activation of Your Nervous System
Over-activation of your nervous system is one of the biggest risk factors for lectin sensitivity. I have many theories why this is the case.
1) Over-activation of your nervous system will cause a ‘leaky gut‘ via the wide variety of effects of the hormone CRH. CRH effects include slower gut flow, less cannabinoid activation (in the amygdala and I suspect in the gut as well) and local inflammation in the gut. Also, CRH will directly cause hormonal dysregulation. The result is lower GnRH, LH, FSH, Pregnenolone, DHEA, Testosterone, Growth Hormone, Thyroid Hormones (T3, T4, TSH) and higher Prolactin and Estrogen.
2) Over-activation of your nervous system will cause lower oxygen or hypoxia in your gut, which will disturb the local gut immune system. This is because blood flow is reduced to your gut when your nervous system increases. Less blood flow also causes less nutrient delivery…Your blood gets shunted to your heart and muscles, while your stomach and liver don’t have what it ideally needs.
3) It will disrupt your sleep. This causes a bunch of downstream problems because sleep is critical to so many other functions.
4) It will disrupt your circadian rhythm (which causes a bunch of downstream problems).
6) It will cause HCL production to decrease. The result is food sensitivities and even more inflammation.
7) It will decrease levels of good hormones and increases some bad ones because they get shunted to cortisol, and indirectly because of circadian and sleep disruption.
In general, oxidative stress and inflammation will cause lectin sensitivity in the gut.
Some mechanisms include:
- Poor mitochondrial function and Oxidative stress,
- Less blood flow,
- Background inflammation….TLR activation, Cytokines, and Nf-kB. TLR activation is a feature of IBS (R), and my guess is that lectins cause this absent infections or biotoxins. MHC I and II/costimulatory molecule activation – which causes immune activation in the gut
- Lower methylation
- Lower Cannabinoid/CB1 activation– explains why people are more likely to be thin and anxious.
- Lower PPAR gamma -explains why people are more likely to be thin,
- Higher STAT3 -explains why people are more likely to be thin and have gut inflammation,
- Lower NAD+/SIRT1– caused by hypoxia, superoxide, worse mitochondrial function, etc…
- Lower Tregs
- Micro biome imbalance
- Lower growth factors: IGF-1, HGH
- Lower serotonin – causes slowed gut flow…Tryptophan gets converted to kynurenine instead of tryptophan. This happens in IBS (R), and my guess is that lectins and stress cause this.
- Higher kynurenine. This happens in IBS (R), and again lectins and stress both cause this.
- Higher CCK…Read: The Positives and Negatives of CCK and Its Role In Lectin Sensitivity
Toll-Like Receptors (TLRs)
Cytokines and various components of the immune system activate TLRs.
As I mentioned, various plant lectins also activate TLRs, especially wheat lectins (R).
How to Know If You’re Lectin Sensitive
There is no ‘smoking gun’ for lectin sensitivity. There are only markers that make you more likely to be lectin sensitive.
Here’s a list of symptoms that are common in people with lectin sensitivity. Lectin sensitivity is on a spectrum, where people are sensitive to it in varying degrees. The more symptoms you have, the higher the likelihood of lectin sensitivity. This list is not comprehensive:
- Gut problems– IBS, IBD…This includes Gas/Abdominal discomfort/Irritated GI tract….This is why an elemental diet has a high cure rate for Crohn‘s.
- Bloating – as a result of inflammation and CCK.
- Autoimmune conditions – IBD, arthritis and Hashimoto’s are probably the most common…
The following are other common symptoms. My current thinking is that lectins are similar to tissues in the hypothalamus, brain stem and other areas in the limbic system. Lectins may cause some autoimmune reaction, which dysregulates the hypothalamus.
I am reasonably confident that dysregulation of the hypothalamus is taking place in most of my sensitive lectin clients. I’m just not sure if it’s because lectins are binding to sugars in these tissues or if our immune system starts getting confused and attacks them.
- Fatigue in the day – even with 8 hours of sleep. Especially post-meal fatigue.. as a result of hypothalamic dysregulation.
- Brain Fog- as a result of hypothalamic dysregulation,
- Lower BMI – usually….Sometimes people with excess BMI have it…those who try to lose weight but can’t no matter what they do or how little they eat…People with mold issues will sometimes gain weight as a result of lower MC4R.
- Cold intolerance- as a result of low T3, increased sympathetic nervous activity and hypothalamic dysregulation,
- Low blood pressure– as a result of hypothalamic deregulation and brain stem oxidative stress,
- Immune imbalances (Th1 dominant or Th2 dominant or Th17 dominant) or any autoimmune condition- very common.
- Excessive anxiety, perfectionism, procrastination, paranoia, OCD and in the inability to let go of thoughts – as a result of hypothalamic dysregulation. These are also indicative of high glutamate and low serotonin.
- Skin problems – indicative of an immune imbalance. Skin problems can include various fungi, eczema, psoriasis, etc…
- Not handling glucose or carbs well (getting hypoglycemic often). Lectins cause havoc on your limbic system, including your hypothalamus, which controls glucose homeostasis.
- Some joint discomfort, even if small… Dr. Gundry says that synovial tissue is very similar to lectins and your immune system gets confused.
- Pain in random places like back aches, etc…. (that aren’t a result of a serious injury, obviously)…This is from increased inflammation.
- Water retention, puffiness around the eyes, extremities- from increased inflammation.
- Some types of headaches/migraines – from increased inflammation.
- Sleep and circadian issues – as a result of hypothalamic dysregulation and increased inflammation.
- Post-nasal drip
- Th1 OR Th2 dominant
People with lectin sensitivity tend to have:
- Higher Adiponectin (over 16) (R).
- Higher TNF-alpha (over 3) (R).
- Higher IL-6 (over 3)- Dr. Gundry has independently noticed this with his lectin sensitive patients.
- Lower White Blood Cells (under 5) – Dr. Gundry has independently noticed this with his lectin sensitive patients. My WBC count went up as I stayed away from lectins. Dr. Gundry and I suspect that the white blood cells are being caught somewhere in the gut, spleen or elsewhere.
- Low free and total T3 (under 3 for free T3) and often higher TSH- Dr. Gundry has independently noticed this with his lectin sensitive patients. Low T3 is a cause and a symptom of lectin sensitivity. Low T3 is because of inflammation and oxidative stress. Dr. Gundry claims that the thyroid tissue is remarkably similar to the lectin proteins and our immune systems get fooled…So we’ll start attacking our thyroid tissue.
- Lower Ferritin (under 70 for men and under 50 for women). Lectins seem to create an inflammatory environment in the gut that reduces iron absorption.
- Lower Insulin (under 4)- in the lectin sensitive who aren’t also leptin resistant.
You can request that your doctor test the levels of the markers listed above. Conventional doctors will look at high or low levels and not mention anything. Sometimes, a lab result may be in the reference range, but not actually be in the optimal range. Reference ranges are not the same as optimal ranges. This is why even values in the ‘normal’ range can be unhealthy and indicate that certain processes in the body aren’t optimal. Lab Test Analyzer will let you know if the levels of a certain marker are optimal and what you can do to get them there if they aren’t.
My Theory On Why Elevated Adiponectin is Associated With Lectin Sensitivity
Dr. Gundry has pointed out that he’s noticed adiponectin as a marker for lectin sensitivity. I have two theories as to why this is the case.
I’ve identified a variation in the Cannabinoid 1 receptor SNP (rs1049353) in my clients with lectin sensitivity. This variation causes the CB1 receptor to not function as well. This SNP is associated with higher adiponectin. Then I found a study showing that Adiponectin increases when you block the CB1 receptor (R).
Hence, Adiponectin is a marker of lectin sensitivity because of the CB1 receptor genetic variations.
In short, when the CB1 receptor doesn’t work well, you will have more gut inflammation and higher adiponectin is a byproduct.
Another variation in the MTHFR genes (mainly rs1801133) are also common in my lectin sensitive clients, which can contribute to under-methylation. One of the effects of under-methylation may be higher adiponectin – as obesity is associated with over-methylation of adiponectin and lower adiponectin production (R). Hence under methylators are more prone to both intestinal issues and higher adiponectin.
As you can imagine, since lectin sensitivity isn’t even a term, there will be absolutely no information on the genetic basis for this issue.
There are many SNPs that can increase risk the for lectin sensitivity, but I will list only a partial list.
The general concept is that lectin sensitivity will increase from variations in SNPs that increase gut inflammation and/or permeability, activate your nervous system, contribute to inflammation, oxidative stress, and circadian rhythm dysregulation.
There are thousands of such SNPs out there, which is why I’m tempted to only list the top two, but the others are meant to give you an idea of what I mean.
Realize that if you have a chronic infection, you needn’t have a strong genetic basis for lectin sensitivity.
Get your 23andme to see which genes you have.
Cannabanoids-CNR1: The Lectin Sensitive Gene (rs1049353)
This is the most significant gene that causes lectin sensitivity in my view.
This SNP is so correlated to lectin sensitivity that I call it the “Lectin Sensitivity Gene.”
Studies indicate that the gut nervous system is the main site of CB1 receptors (R).
Only about 14% of the global population will have a T allele, but about 40% of whites have a T allele.
About 85% of my clients who don’t have an infectious issue have the T or minor allele. Even among my white clients who have infections, they are still more likely to have the minor allele.
I have TT or two minor alleles, which will be pretty rare (less than 2% of the global population).
MTHFR (rs1801133, rs1801131)
This is the second most important gene involved in lectin sensitivity.
I have two minor alleles of the MTHFR C677T SNP, which maybe 8% of the population has.
Methylation supposedly breaks down histamine in the gut. Histamine in the gut causes increased intestinal permeability.
So under methylation will increase the likelihood of lectin-sensitivity.
Since these SNPs are associated with anxiety disorders, it could also have some indirect effects through over-activation of the nervous system.
COMT V158M (rs4680)
I suspect the A allele of this COMT SNP causes more psychological stress, which leads to an overactivity of the nervous system.
The SOD2 SNPs will contribute to lectin sensitivity risk via increasing superoxide.
rs3791124 Glycine A=0.1619 AG
STAT3 gene will cause increased gut inflammation and also make you more likely to be thin.
rs9891119 STAT3 C=0.3714 CC
MHC SNPs will increase likelihood of immune activation….
- rs2395185 MHC/HLA-DR T=0.2929 TT
- rs10484554 MHCI…HLA-C T=0.1112 CT
- rs3135388 MHCI…HLA DRB1*1501 A=0.0429 AG
- rs3135391 MHCI…HLA-DRB1*1501 A=0.0463 AG
rs1801260 CLOCK G=0.2181 AG – this SNP…
Each G=higher activity levels in the evening, lower motility, lower HR, lower diastolic BP, delayed breakfast time….these are common features in people who are lectin sensitive.
There are many other SNPs that I found more likely in lectin sensitivity, but they’re beyond the scope of this post. Suffice it to say that there’s a wide range of genes that play into the degree of lectin sensitivity that you may have.
The point in bringing down examples of SNPs is so that you can get an idea of different classes of SNPs that will be more likely in the lectin sensitive.
To learn more about your SNPs, run a 23andme test and upload your raw data into SelfDecode.
The new SelfHacked Lectin Avoidance Diet cookbook goes into more details about this.
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