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How to test for Celiac Disease?

The only way you can get a definite YES or a NO for Celiac Disease (CD) is by doing intestinal biopsy. As this is an invasive and expensive procedure, many prefer measuring serum antibodies as an initial screening process. When someone decides to test for antibodies against gluten it is necessary to keep in mind:

a) that the gluten protein is fairly complex and thus all antibodies need to be tested

b) that the blood test is not a substitute for the biopsy.

Whichever assessment method one decides to use it is important to know that:

For CD, early diagnosis means early intervention with treatment and prevention of long-term complications, including the development of severe and irreversible phenotypes and of other autoimmune disorders.” (Ventura A et al., 2010)

 

Intestinal biopsy is the golden standard for diagnosing Celiac Disease.

 

An individual is classified as celiac when a biopsy of the duodenal mucosa is taken which detects:

a) a reduction or disappearance of intestinal villi &

b) intraepithelial lymphocytes (IELs) higher than 25/100 enterocytes (Sapone A. et al., 2012).

Individuals presenting with significant villous atrophy are classified as CD March stage III, whereas normal villi but increased number of intraepithelial lymphocytes are classified as Marsh I or II (Hill ID et al., 2005). Marsh type II may also suffer from CD but positive serological tests is needed to strengthen the diagnosis (Hill ID et al., 2005). When only elevated IELs are observed but no damage of the intestinal lining, it is difficult to diagnose CD (Kakar eta l., 200). In literature this state is usually referred to as latent CD (Dewar et al., 2005) and further testing is required.

 

Can elevated IELs be due to a different cause other than Celiac Disease?

The presence of IELs can be due to gastrointestinal inflammation caused by H. pylori (Memeo et al., 2005) or tropical sprue (Ross et al., 1981). Unexplained neurological or psychiatric disorders such as autism, schizophrenia, and cerebellar ataxia (Cascella N et al., 2009, Burk K et al., 2009, Genuis S and Bouchard T, 2010) are also linked with elevated IELs and no mucosal damage.

 

Can a blood test confirm Celiac Disease?

No. However, a lot of the time serum antibody testing is used in the screening process. The ones necessary are: anti-DGP IgG & anti-tTG IgA

 

Antibodies for the diagnosis of Celiac Disease

Antibodies

Accurate

Not affected by IgA deficiency

Not prone to interpretation

Cheap

Appropriate for children <2 years old

AGA IgA

AGA IgG

EMA IgA

tTG IgA

DGP IgG

Anti-Actin IgA

 

 

classic Anti-gliadin (AGA) antibody IgA

Pros:

1. relatively cheap

Cons:

1. found in healthy individuals (Bizzaro N et al., 2012)

2. May fluctuate within the first 2 years of age (Simell et al., 2007)

3. relatively insensitive (Fasano A, 2013)

 

AGA-IgG

Pros:

1. useful for pediatric patients with CD who test negative for anti-tTG (Carlsson A et al. 2001, Lagerqvist C et al., 2008).

2. useful in patients with IgA deficiency (Villalta D et al., 2007).

3. reasonably cheap

3. Same results where obtained with the DGP IgG test (Liu E et al., 2007, Agardh D 2007, Basso D et al., 2009, Naiyer A et al., 2009).

4. Remains constant the first 2 years of age (Simell et al., 2007)

Cons:

1. relatively insensitive (Fasano A, 2013)

 

EmA (Endomysial Antibodies – antigliadin) IgA (unless IgG requested)

Pros:

1. It is equally specific with the anti-tTG antibodies, meaning it recognizes the same antigens (Hill 2005)

Cons:

1. It is prone to subjective interpretation

2. It is less sensitive than the anti-tTG (Biagi F et al., 2001, Baudon J et al., 2004, Lock et al., 2004, Kaukinen K et al., 2007).

3. Not accurate in patients with selective IgA deficiency.

4. May fluctuate within the first 2 years of age (Simell et al., 2007)

5 *The IgG version has inferior sensitivity (Fasano A, 2013)

 

anti-tTG (antihuman tissue transglutaminase) IgA (unless IgG requested)

Pros:

1. As it is quantitative, automated and not prone to subjective interpretation

2. high diagnostic sensitivity (95%) specificity (97%) (Tozzoli et al., 2010)

Cons:

1. Anti-tTG IgA is not sensitive enough to be used alone and the addition of the anti-DGP IgG test would increase the accuracy for CD especially in children (Niveloni S et al., 2007, Villalta D et al., 2007, Volta U et al., 2010, Tonutti E et al., 2009, Villalta et al., 2010, Maglio M et al., 2010)

2. May fluctuate within the first 2 years of age (Simell et al., 2007)

3 *The IgG version has inferior sensitivity (Fasano A, 2013)

 

DGP antibodies IgG (deamidated gliadin peptide)

Pros:

1. antibodies comparable sensitivity and specificity to anti-tTG and EMA (Sugai E et al., 2006)

2. Remains constant the first 2 years of age (Simell et al., 2007)

3. DGP IgG test positive in 80% of cases of CD patients with IgA deficiency as compared to 40% for AGA IgG ( Villalta et al., 2010)

 

ANTI-ACTIN IgA

Pros: can evaluate the severity as it is related to the severity of intestinal damage (Granito A et al., 2004, Carroccio A et al., 2005)

Cons: limited usefulness for diagnosis

 

In monitoring of patients on a gluten-free diet, positivity with a low titer of anti-DGP antibodies suggests that the diet should be reassessed, even if the anti-tTG test is negative” (Tursi et al., 2006)

 

Interpretation of serological and biopsy test results

Biopsy

+

Serology

+

CD

Absence of CD and possible false-positive blood test. A negative genetic test can strengthen the negative diagnosis.

This result is treated as CD. However, inflammation in the lining can be due to other causes, including intolerances to other foods.

No CD. However, in the presence of other autoimmune conditions or genetic predisposition, future monitoring may be appropriate.

 

Which other blood biomarkers are available?

While the tests above are the ones most commonly done there is evidence that more thorough testing may be needed for those with negative results and positive symptoms. A complete antibody screening should include: Alpha gliadin, Omega gliadin, Gamma gliadin, Deamidated gliadin, TG2, TG3, TG6.

 

Deamidation is an acid or enzymatic treatment used by the food processing industry to make wheat, water-soluble so it mixes with other foods. It has been shown to cause severe immune responses to people (Leduc V et al., 2003).

Gliadin is broken down to alpha, omega and gamma fractions. If a lab tests only for alpha gliadin antibodies the results may be misleading (Quartesn H et al. 2001).

Elevated antibodies of TG2 indicated a reaction against the intestinal track (Thomas H et al., 2011). Transglutaminase 3 (TG3) is found in the skin. An autoimmune reaction to skin may lead to skin disorder known as dermatitis herpetidormis, which presents as itchy red blisters found usually in the knees, elbows, buttocks but can appear anywhere on the body (Stamnaes I et al., 2010). Elevated antibodies to transglutaminase 6 indicate an immune response against the nervous system (Alessio et al., 2012).

Leaky gut: the trojan horse to food allergies?

Leaky Gut is a digestive track with a compromised permeability (like a hose with holes).

 

While the SYMPTOMS OF A LEAKY GUT ARE NOT ONLY ASSOCIATED WITH DIGESTION many people suffering from it experience food sensitivities. That’s why in my opinion:

  1. Elimination diets (i.e. FODMAP, low oxalate, low histamine diets) do not work long term: foods that cause reactions are removed but the reason why the reaction was there are 1st place stays.
  2. Most chronically ill patients have restricted diets: the body is not able to renew the epithelial tissue in the gut  leading to poor gut integrity ➛ increased gut permeability  ➛ food sensitivities.
  3. Diversity in gut flora is positively associated with health: A diverse gut flora supports gut integrity.

 

The reason why the above hold true can be traced to the double role of the gut:

  1. digest and absorb nutrients
  2. host part of the immune system

The immune system in the gut has the delicate role of balancing between: Tolerating or Reacting to the foods it comes in contact with. The evolutionary benefit of this role is the following:

Foods we consume can be degraded or containing toxins and thus be poisonous to the body. In these cases the activation of the immune system can kill the pathogenic substances and protect us.  This process is mediated through a series of steps leading to the increase of intestinal permeability.

 

Unfortunately in certain people the same reaction is triggered not only by toxins but also by regular foods. In these cases after the consumption of the “trigger food” the individual experiences a reaction such as: foggy brain, bloatness, diarrhea, stomach cramps, increased heart rate, running nose, anxiety, irritability. Reducing gut permeability (i.e. healing leaky gut) can make previous “trigger foods” tolerable again.

 

Testing for leaky gut.

Our gut wall consists of just one cell thick epithelial tissue (Sturgeon, C. and Fasano, A., 2016) . The space between each epithelial cell is called tight junction.

 

Lactulose/Mannitol test

The test that has been used the longest for detecting leaky gut is the lactulose/mannitol urine test. The test is simple: after an overnight (12 hour) fast you collect the urine then have a solution of lactulose & mannitol and 6 hours later you collect the urine again.

Mannitol enters the body through the epithelial cell membrane, while lactulose goes through the tight junctions (FlemIng, S.C. et al., 1990)

The loss of absorptive areas ➛ ↓ the absorption of mannitol.

The loss of mucosal integrity ➛ ↑ lactulose absorption.

 

An elevated lactulose : mannitol ratio indicates the presence of leaky gut. The test is available from many labs including Genova Diagnostics. The results can be affected by the use of  NSAIDS, alcohol and according to Dr. Alesio Fasano the results are very sensitive to the collection process and thus may not be reliable when done outside a lab.

 

3 stool markers of leaky gut (α1-Antitrypsin – sIgA – calprotectin)

 

α1-Antitrypsin

is a protein of the liver. When detected in stool (sourced from the intestines) it indicates a severe case of intestinal permeability and thus is not a sensitive enough marker of leaky gut (Biancone, L. et al., 2003)

sIgA

is part of the immune system and functions as a tag for substances that need to be excreted.

Calprotectin

is a protein linked with intestinal inflammation. It is used to distinguish between IBD & IBS (Leblhuber, F., et al., 2015).

3 blood markers of leaky gut (Zonulin – LPS – DAO)

 

Zonulin

Zolulin is a protein responsible for the modulation of tight junctions (Sturgeon, C. and Fasano, A., 2016).

↑ levels of Zonulin ➛ Opening of tight junctions ➛ influx of dietary & microbial antigens in the blood

 

The 2 main triggers of Zonulin release have been found to be:

  1. Bacteria: including Eschericha coli, lab E. coli, virulent E. coli, and Salmonella typhi (El Asmar et al. 2002)
  2. Gliadin: a protein found in gluten (Clemente, M et al., 2003)

Elevated levels of Zonulin have been linked in literature (Sturgeon, C. and Fasano, A., 2016) to:

  1. autoimmune conditions such as: Type 1 Diabetes, Celiac Disease, Multiple Sclerosis, Intestinal Bowel Diseases
  2. metabolic disorders such as: Obesity & PCOS
  3. Asthma
  4. Coronary Heart Disease
  5. Systemic infections
  6. Gluten Sensitivity
  7. Necrotizing Enterocolitis
  8. Brain cancer (Skardelly, M et al., 2009) by altering the integrity of the Blood Brain Barrier.

 

Lipopolysaccharide Bacterial Endotoxin

Lipopolysaccharide (LPS) is a component of the wall of gram-negative bacteria (Trent, M.S et al., 2006) responsible for the activation of the innate immune system. LPS have 3 regions. Lab tests measure the lipid A region which is also known as endotoxin. Germ-negative bacteria live in the lumen of the gut but should not be found in the blood. Detection of LPS endotoxins in the blood is sign of leaky gut.

 

DAO

Dunwoody Labs measures the levels of DAO enzyme in their intestinal permeability test. DAO is responsible for the break down of histamine. Histamine while necessary for good gut health when elevated can cause problems. Low levels of DAO thus is also a sign of leaky gut. Genetic polymorphisms in the AOC1 gene (which encodes the DAO enzyme) can impair the body’s ability to produce the DAO. Those with low levels can check their genetic burden using the table bellow.

source: InstagramOpus23

 

The future of leaky gut testing

While not currently available for the general public I-FABP is a marker of gut permeability used in laboratories. Intestinal fatty acid binding protein (I-FABP), is a marker of early enterocyte cell death (Derikx, J.P. et al., 2010)

 

 

How to support leaky gut.

When it comes to supporting leaky gut I like to split the nutrients in 2 categories:

  1. the ones affecting the mechanisms that cause the problem (these are the ones that ultimately will heal the intestines)
  2. the ones that suppress the symptoms – commonly referred to as anti-inflammatory (these are the ones that should help ameliorate the symptoms)

 

Avoid trigger foods

While I consider elimination diets not a good idea long-term in the short run it is important to remove any trigger foods to control inflammation. IgG food intolerance tests can be very useful for that matter.

 

Probiotics

I consider the use of probiotics the most potent yet the most tricky in implementation among all interventions. Certain probiotic strains have been found to induce cell proliferation in gut cells:

Bifidobacterium breve R0070 & Lactococcus lactis R1058 when taken taken together seem to have synergistic effects and both can be found in the Jarrow-Dophilus EPS. (Grimoud, J. et al., 2010 *)

Some others that were shown to suppress inflammation induced by LPS levels are:

  1. Bifidobacterium longum subsp. Infantis, Bifidobacterium longum, Bifidobacterium bifidum, Lactobacillus rhamnosus – in the order mentioned (Laetitia, R. et al., 2013)
  2. Lactobacillus reuteri strain, ATCC PTA 6475 – available from Biogaia. (Thomas, C.M. and Versalovic, J., 2010)
  3. Bifidobacterium infantis 35624 (Groeger, D. et al., 2013)

 

* The French study by Julien Grimoud is a goldmine of information.

 

Mushrooms

Edible & medicinal mushrooms have been shown to activate & modulate the  immune system in the gut acting this way as anti-inflammatory in LPS toxicity.  A. bisporus, C. cibarius and L. deliciosus (Saffron Milkcap mushroom) are mushroom extracts available in supplemental form (Moro, C. et al., 2012).

Berberine

Berberine is an alkaloid found in some plants shown to inhibit the inflammatory effects of LPS (Mo, C. et al., 2014Wu, Y.H., et al., 2012). Berberine has been shown to interact with 57 genes, so cross-checking polymorphisms related to other symptoms is worth doing.

 

 

 

 

 

 

 

 

 

 

source: Opus23

 

Other agents

Quercetin & CoQ10 were also shown to have anti-inflammatory effects in  LPS toxicity (Abd el-gawad, H.M. and Khalifa, A.E., 2001). Fish Oils were shown to restore intestinal integrity by increasing DAO enzyme concentration in the gut (Liu, Y. et al., 2012).

 

L-glutamine

L-glutamine acts as fuel for intestinal cells (Larson, S.D, et al., 2007) and to that extent supplementation can benefit leaky gut. Gradually building the dosage from as little as 2.5 gr per day to 20 gr should be a safe way to avoid adverse reactions. I have not seen any studies demonstrating the benefits of L-glutamine supplementation for leaky gut however it does support overall intestinal health.

 

Larazotide acetate

Larazotide acetate is a protein shown to inhibit Zonulin production without any adverse effects (Paterson, B.M et al., 2007). Alba Therapeutics an Indian pharmaceutical company is in the process of developing a drug with this protein.

 

 

References

Abd el-gawad, H.M. and Khalifa, A.E., 2001. Quercetin, coenzyme Q 10, and l-canavanine as protective agents against lipid peroxidation and nitric oxide generation in endotoxin-induced shock in rat brain. Pharmacological research, 43(3), pp.257-263.

 

Biancone, L., Fantini, M., Tosti, C., Bozzi, R., Vavassori, P. and Pallone, F., 2003. Fecal α1-antitrypsin clearance as a marker of clinical relapse in patients with Crohn’s disease of the distal ileum. European journal of gastroenterology & hepatology, 15(3), pp.261-266.

 

Clemente, M.G., De Virgiliis, S., Kang, J.S., Macatagney, R., Musu, M.P., Di Pierro, M.R., Drago, S., Congia, M. and Fasano, A., 2003. Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function. Gut, 52(2), pp.218-223.

 

Derikx, J.P., Luyer, M.D., Heineman, E. and Buurman, W.A., 2010. Non-invasive markers of gut wall integrity in health and. World J Gastroenterol, 16(42), pp.5272-5279.

 

El Asmar, R., Panigrahi, P., Bamford, P., Berti, I., Not, T., Coppa, G.V., Catassi, C. and Fasano, A., 2002. Host-dependent zonulin secretion causes the impairment of the small intestine barrier function after bacterial exposure. Gastroenterology, 123(5), pp.1607-1615.

 

FlemIng, S.C., Kapembwa, M.S., Laker, M.F., Levin, G.E. and Griffin, G.E., 1990. Rapid and simultaneous determination of lactulose and mannitol in urine, by HPLC with pulsed amperometric detection, for use in studies of intestinal permeability. Clinical chemistry, 36(5), pp.797-799.

 

Grimoud, J., Durand, H., De Souza, S., Monsan, P., Ouarné, F., Theodorou, V. and Roques, C., 2010. In vitro screening of probiotics and synbiotics according to anti-inflammatory and anti-proliferative effects. International journal of food microbiology, 144(1), pp.42-50.

 

Groeger, D., O’Mahony, L., Murphy, E.F., Bourke, J.F., Dinan, T.G., Kiely, B., Shanahan, F. and Quigley, E.M., 2013. Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut. Gut microbes, 4(4), pp.325-339.

 

Laetitia, R., Paul, A., Marinescu, D., Shao, W. and Prakash, S., 2013. Effect of probiotics Lactobacillus and Bifidobacterium on gut-derived lipopolysaccharides and inflammatory cytokines: an in vitro study using a human colonic microbiota model. Journal of microbiology and biotechnology, 23(4), pp.518-526.

 

Larson, S.D., Li, J., Chung, D.H. and Evers, B.M., 2007. Molecular mechanisms contributing to glutamine-mediated intestinal cell survival. American Journal of Physiology-Gastrointestinal and Liver Physiology, 293(6), pp.G1262-G1271.

 

Leblhuber, F., Geisler, S., Steiner, K., Fuchs, D. and Schütz, B., 2015. Elevated fecal calprotectin in patients with Alzheimer’s dementia indicates leaky gut. Journal of Neural Transmission, 122(9), pp.1319-1322.

 

Liu, Y., Chen, F., Odle, J., Lin, X., Jacobi, S.K., Zhu, H., Wu, Z. and Hou, Y., 2012. Fish oil enhances intestinal integrity and inhibits TLR4 and NOD2 signaling pathways in weaned pigs after LPS challenge. The Journal of nutrition, 142(11), pp.2017-2024.

 

Mo, C., Wang, L., Zhang, J., Numazawa, S., Tang, H., Tang, X., Han, X., Li, J., Yang, M., Wang, Z. and Wei, D., 2014. The crosstalk between Nrf2 and AMPK signal pathways is important for the anti-inflammatory effect of berberine in LPS-stimulated macrophages and endotoxin-shocked mice. Antioxidants & redox signaling, 20(4), pp.574-588.

 

Moro, C., Palacios, I., Lozano, M., D’Arrigo, M., Guillamón, E., Villares, A., Martínez, J.A. and García-Lafuente, A., 2012. Anti-inflammatory activity of methanolic extracts from edible mushrooms in LPS activated RAW 264.7 macrophages. Food Chemistry, 130(2), pp.350-355.

 

Paterson, B.M., Lammers, K.M., Arrieta, M.C., Fasano, A. and Meddings, J.B., 2007. The safety, tolerance, pharmacokinetic and pharmacodynamic effects of single doses of AT‐1001 in coeliac disease subjects: a proof of concept study. Alimentary pharmacology & therapeutics, 26(5), pp.757-766.

 

Skardelly, M., Armbruster, F.P., Meixensberger, J. and Hilbig, H., 2009. Expression of zonulin, c-kit, and glial fibrillary acidic protein in human gliomas. Translational oncology, 2(3), pp.117-120.

 

Sturgeon, C. and Fasano, A., 2016. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers, p.e1251384.

 

Thomas, C.M. and Versalovic, J., 2010. Probiotics-host communication: Modulation of signaling pathways in the intestine. Gut microbes, 1(3), pp.148-163.

 

Trent, M.S., Stead, C.M., Tran, A.X. and Hankins, J.V., 2006. Invited review: diversity of endotoxin and its impact on pathogenesis. Journal of endotoxin research, 12(4), pp.205-223.

 

Wu, Y.H., Chuang, S.Y., Hong, W.C., Lai, Y.J., Chang, G.J. and Pang, J.S., 2012. Berberine reduces leukocyte adhesion to LPS-stimulated endothelial cells and VCAM-1 expression both in vivo and in vitro. International journal of immunopathology and pharmacology, 25(3), pp.741-750.

What helps Histamine Intolerance?

Histamine is a hormone involved in digestion, immune & nervous system function. While anti-histamine drugs are often prescribed for asthma, they are also given to those with food allergies.

 

Anti-histamine drugs can be life saving in times of crisis. At the same time if one doesn’t deal with what causes the reaction at 1st place she/he is trying to put off a fire by removing the battery from the fire alarm.
Which raises the question “What helps histamine intolerance?”

 

What is Histamine Intolerance?

Histamine is a hormone with varying functions in different tissues.

 

Histamine intolerance symptoms are due to histamine’s relation with the immune system. Histamine activates immune cells (basophils & mast cells) while causing blood vessels to dilate so that immune cells can be quickly transferred to kill pathogens. In that sense you can think of histamine as a fire alarm.

“Histamine intolerance is a fire alarm going on when there is no fire.”

 

To be more precise histamine intolerance results from imbalance between accumulated histamine and the capacity to break it down. In most cases it is due to limited histamine breakdown capacity. Like all hormones histamine needs to be eliminated from the body when it has done its job. While it is broken down by a few different enzymes (HNMT, NAT1,2 & DAO), it is the DAO (Maintz, L. and Novak, N., 2007) responsible for the breakdown of ingested histamine.

 

Histamine’s link with Digestion.

Gastrointestinal problems are very common among those with histamine intolerance.

While histamine is necessary for proper gut function excess levels can cause digestive complications. Bellow are a few facts highlighting the link between histamine intolerance and gut health:

a. all 4 histamine receptors H1R-H4R are found in the digestive track and they have excitatory actions there (Breunig E. et al., 2007).

b. In a study conducted in Italy, 13 out of 14 subjects (with food intolerances) reported benefits in at least 1 food after DAO supplementation (Manzotti G. et al., 2015).

c. The capacity of both histamine breakdown pathways: HNMT and DAO have been reported to be reduced in those with food intolerances (Kuefner MA et al., 2004).

d. Elevated levels of histamine in the brain have been shown to suppress appetite. (Malmlöf, K. et al., 2005)

 

“Diet can help histamine intolerance in 2 ways: i. reduce the histamine load ii. support histamine breakdown”

 

Histamine Intolerance foods to avoid

 

There are 2 categories of foods those with histamine intolerance need to avoid: a. Those that contain histamine & b. those that can cause the release of histamine in the body although they don’t contain histamine (Maintz, L. and Novak, N., 2007)

#Foods to be avoided with Histamine IntoleranceContain HistamineLow in Histamine (but may trigger its release)DAO blockingVegetarianVeganFruits
Vinegar containing foods (ie pickles, mayonnaise, olives)XXX
Fermented foods (ie saurkraut, soy sauce, kombucha, kefir, yogurt)XXXX
Fermented foods (ie saurkraut, soy sauce, kombucha, kefir, yogurt)XX
Cured Meats (ie bacon, salami, hot dogs)X
Soured foods (ie sour cream, sour milk, buttermilk)XX
Dried fruitXXXX
Aged cheese (ie gouda, camembert, cheddar, goat cheese)XX
Nuts (walnuts, cashews, peanuts)XXX
Smoked fish & shellfishX
Chickpeas, soybeansXXX
Banana, Papaya, Pineapple, StrawberriesXXXX
ChocolateXXX
Cow's milkXX
TomatoesXXX
Black, green, mate teaXXX

 

Histamine Intolerance diet

The fresher the food the lower it is in histamine. Vitamin C supplementation has also been shown to reduce histamine levels (Hemilä, H., 2014).

#Diet for Histamine IntoleranceVegetarianVegan
Fresh cooked meat, poultry
Fresh caught fish
EggsX
Gluten free grains: rice, quinoaXX
Fresh fruits (ie mango, pear, watermelon, apples)XX
Fresh veggies (except: tomatoes, eggplant, spinach, avocado)XX
Dairy substitutes (ie coconut m rice, hemp, almond milk)XX
Cooking oils (olive & coconut)XX
Herbal teasXX

 

Blood sugar regulation and Histamine Intolerance

The link between histamine and diabetes goes back to the 1950 (Pini A et al., 2016).

Plasma histamine was shown to reduce after insulin administration in diabetic rats (Hollis T. et al., 1985). Two of the mechanisms through which insulin and histamine interact was that the activation of histamine 3 receptors (H3R) in pancreatic beta cells was shown to: a. inhibit insulin secretion (Nakamura T et al., 2014) b. reduce glucagon production in non-hyperglycemic state (Nakamura T et al., 2015). While the mechanisms of interaction between diabetes and histamine intolerance are currently not clear the correlation appears to be positive (Pini A et al., 2016).

To that extent a state of insulin resistance should be addressed in cases of histamine intolerance together with any other protocol.

 

How to test for Histamine Intolerance

Prior to treating any condition it is wise to diagnose it first. By measuring the levels of DAO enzyme in your blood you can assess your body’s capacity to breakdown histamine. The cut off level of serum DAO activity (for probable histamine intolerance) is <10 U/mL (Manzotti G. et al., 2015)

 

Labs that offer this service are:

Smart Nutrition in UK

ImmunoPro in Australia

Dunwoody Labs in US & UK (via Invivo clinical)  – In my opinion the best test for gut integrity currently available.

 

23andme results & Histamine Intolerance

23andme results can be useful in identifying potential blockages in the pathway of histamine. At the same time it is dangerous to drive conclusions solely from one’s genetic make up, let alone one gene. In many cases a person may have no SNPs in the gene that produces the DAO enzyme (AOC1 gene) and at the same time experience histamine-like reactions after the consumption of red wine for instance. The case bellow is such an example.

The woman is in her mid 40s, vegetarian with a more or less healthy lifestyle. She carries only 1 homozygous polymorphism in the AOC1 gene which has been shown to be beneficial.

 

Source: Opus23

 

While there seems to be no burden on the production of DAO if you look at the entire pathway you will see that she carries SNPs in the HNMT and MAOB genes. Both of which can tax DAO’s function.

 

Source: Opus23

 

How can this information be useful? 

For this woman supporting the function of HNMT and MAOB can help with histamine symptoms. For HNMT methylation support as well Salacia Oblonga (Oda, Y et al., 2015)  can be used while for MAOB vit B2.

 

Source: Opus23

 

This Nutrigenomics analysis would not be possible without access to Opus23 analytics.

 

 

References

Breunig, E., Michel, K., Zeller, F., Seidl, S., Weyhern, C.W.H.V. and Schemann, M., 2007. Histamine excites neurones in the human submucous plexus through activation of H1, H2, H3 and H4 receptors. The Journal of physiology583(2), pp.731-742.

 

Hemilä, H., 2014. The effect of vitamin C on bronchoconstriction and respiratory symptoms caused by exercise: a review and statistical analysis. Allergy, Asthma & Clinical Immunology10(1), p.58.

 

Hollis, T.M., Kern, J.A., Enea, N.A. and Cosgarea, A.J., 1985. Changes in plasma histamine concentration in the streptozotocin-diabetic rat. Experimental and molecular pathology, 43(1), pp.90-96.

 

Kuefner, M.A., Schwelberger, H.G., Weidenhiller, M., Hahn, E.G. and Raithel, M., 2004. Both catabolic pathways of histamine via histamine-N-methyltransferase and diamine oxidase are diminished in the colonic mucosa of patients with food allergy. Inflammation Research, 53, pp.S31-S32.

 

Malmlöf, K., Zaragoza, F., Golozoubova, V., Refsgaard, H.H.F., Cremers, T., Raun, K., Wulff, B.S., Johansen, P.B., Westerink, B. and Rimvall, K., 2005. Influence of a selective histamine H3 receptor antagonist on hypothalamic neural activity, food intake and body weight. International journal of obesity, 29(12), pp.1402-1412.

 

Manzotti, G., Breda, D., Di Gioacchino, M. and Burastero, S.E., 2015. Serum diamine oxidase activity in patients with histamine intolerance. International journal of immunopathology and pharmacology, p.0394632015617170.
Maintz, L. and Novak, N., 2007. Histamine and histamine intolerance. The American journal of clinical nutrition, 85(5), pp.1185-1196.

 

Pini, A., Obara, I., Battell, E., Chazot, P.L. and Rosa, A.C., 2016. Histamine in diabetes: is it time to reconsider?. Pharmacological research111, pp.316-324.

 

Nakamura, T., Yoshikawa, T., Noguchi, N., Sugawara, A., Kasajima, A., Sasano, H. and Yanai, K., 2014. The expression and function of histamine H3 receptors in pancreatic beta cells. British journal of pharmacology, 171(1), pp.171-185.

 

Nakamura, T., Yoshikawa, T., Naganuma, F., Mohsen, A., Iida, T., Miura, Y., Sugawara, A. and Yanai, K., 2015. Role of histamine H 3 receptor in glucagon-secreting αTC1. 6 cells. FEBS open bio, 5, pp.36-41.

 

Oda, Y., Ueda, F., Utsuyama, M., Kamei, A., Kakinuma, C., Abe, K. and Hirokawa, K., 2015. Improvement in Human Immune Function with Changes in Intestinal Microbiota by Salacia reticulata Extract Ingestion: A Randomized Placebo-Controlled Trial. PloS one, 10(12), p.e0142909.

 

 

 

Underactive thyroid and gut health

The relationship between underactive thyroid and gut health is reciprocal. While a compromised thyroid health will affect the gut function, the reverse also holds true.

How does an underactive thyroid affect the gut

i. For proper digestion of protein the stomach needs to secrete hydrochloric acid (HCl) – a very expensive energy-wise process. When the thyroid is underactive the production of HCl is low (hypochloridia)  (1). The implications of hypochloridia are massive as undigested proteins can cause increased intestinal permeability in the gut.

ii. Underactive thyroid will slow down other high energy demanding processes in the body such as liver and gallbladder function (2,3). The consequence is poor fat digestion and detoxification.

 

“Whatever the reason of the cause, slow thyroid function will compromise macronutrient digestion”

 

How can poor gut health cause hypothyroidism

i. While most of the T4 (inactive form of thyroid hormone) is activated in the liver, 20% of the conversion takes place in the intestines, in the presence of healthy gut flora.

ii. Inflammation in the gi track can exhaust the adrenals (4) which will then drug down the function of thyroid.

iii. Constipation can compromise the elimination of estrogen from the body. High estrogen levels by binding to thyroid hormone receptors can slow down thyroid function.

iv. Faulty digestion is one of the primary causes of autoimmune disease (5,6). With 60% of the immune system located in the gi track this should come as no surprise. Hashimoto’s is an automimmune disorder where the body attacks the TPO enzyme in the thyroid gland.

v. Elevated levels of Yersinia enterocolitica bacteria have been associated with patients suffering from Hashimoto’s disease (7).

 

 How to address hypothyroid-gut issues

Nobel prize winner and microbiologist Elie Metchnikoff said: “Death begins in the colon.” But so does health. Healing the gut should be your primary concern if you are presenting with gi and thyroid problems. A comprehensive stool analysis is a great starting point.

 

Knowing how underactive thyroid can put a burden on gut health what can you do?

If you suffer from gastrointestinal problems make sure your thyroid function is good shape. While supplementation and natural remedies can support digestion initially, on the long run you want the body to produce adequate levels of HCl and digestive enzymes. If underactive thyroid symptoms are present work with a healthcare practitioner to improve your thyroid health.

 

 

 

References

1. Atrophic body gastritis in patients with autoimmune thyroid disease: an underdiagnosed association. Arch Intern Med 1999 159:1726-1730.

2. Possible chronic thyroiditis revealed by [18F]-FDG-PET/CT scan in a euthyroid patient with recurrent gallblader carcinoma. Thyroid 2007 17:1157-1158.

3. Is bile flow reduced in patients with hypothyroidism? Surgery 2003, 133: 288-293.

4. Chronic fatigue syndrome: inflammation, immune function, and neuroendocrine interactions. Curr Rheumatol Rep 2007 9:482-487.

5. The gut immune system and type 1 diabetes. Ann NY Acad Sci 2002; 958:39-46.

6. The “perfect storm” for type 1 diabetes: the complex interplay between intestinal microbiota, gut permeability and mucosal immunity. Diabetes 2008;57:2555-2562.

7. Clin Microbiol Infect 2001 Mar 7:138-143.

 

Did you have your tonsils removed?

What are the tonsils?

Tonsils are a collection of lymphoid tissue in the upper part of the gastrointestinal track. In some kids they get inflamed in which case an operation called tonsillectomy removes them letting them live happily ever after.

As common as tonsillectomy might be its implications go beyond the removal of the lymphoid tissue at the back of our mouth. In a study analyzing 3,963 children in Netherlands those that underwent an (adeno)tonsillectomy between the age of 0 and 7 had a higher risk for been overweight at the age of 8 (1).

What could be the link then between having one’s tonsils removed and struggling with weight management?

Tonsils form part of the immune system participating in its function of recognition and rejection of foreign organisms. Removal of tonsils potentially by compromising the presence of antibodies in the gut (2) may be affecting the intestinal microflora and thus contributing to metabolic dysregulation (3).

While more research is needed to establish the consequences of tonsils removal given that tonsils are part of the immune system (70% of which resides in the gut) checking the gut flora is a good place to start, when faced with immunological or metabolic challenges.

 

 

1. Wigja A (2009) Adenotonsillectomy and the Development of Overweight. Pediatrics, 123: 1095 -1101.

2. Scadding G (1990) Immunology of the tonsil: a review. Journal of the Royal Society of Medicine, 83.

3. Nieuwdrop M et al. (2014) Role of Microbiome in Energy Regulation and metabolism, gastroenterology, 146: 1525-1533.