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Reversing Vitiligo

(Updated: 18th Dec 2017)

Vitiligo (also called “leukoma”) is an autoimmune condition where loss of pigment from areas of the skin result in irregular white patches, the texture of which remain normal. Similar with all autoimmune disorders:

i. the body is attacking its own tissue. In the case of vitiligo the body is attacking the melanocytes (the cells responsible for skin colouring).

ii. the triggering cause may vary. I have seen 1 case where it started after a car accident at an early stage of life & another where it developed after a stressful period at late 40s.

iii. the development of the disease is the result of genetic predisposition as well as environmental factors.

iv. there is a higher than normal risk for the simultaneous presence of other autoimmune conditions.

 

Cease (the autoimmune) Fire.

As an autoimmune condition vitiligo has to be treated as an immunological problem and not solely as a skin one. While the symptoms manifest in the skin it is the immune system that is over-reacting. This is the reason why in many cases immunosuppressive drugs are prescribed (Boone B., et al., 2007). Stopping the over-activity of the immune system may not be as straight forward as we wish. Foods, heavy metals, infections have been shown or speculated to be the root cause of this unfavourable behaviour of the immune system (IS).

In order to address each of the above one can:

i. follow an elimination diet for foods.

ii. remove any obvious toxic deposits in the body (i.e. mercury fillings, tattoos)

iii. get tested for carrying any of the common viruses associated with autoimmunity (i.e. Epstein Barr virus)

This is the 1st step of the ROSE system I base most cases on (i.e. Removal of ongoing pathogens).

 

Which nutrients can help & why?

In search for re-pigmentation solutions for vitiligo, a group of scientists in Amsterdam – NL (Cormane R et al., 1985), noted that patients with phenylketonuria (who among other symptoms have lighter than normal skin) when administrated tyrosine and were incubated with UV-light had normal melanin production. Cormane’s team initially tried the tyrosine & UV-A protocol in a pilot study of 5 without any success. Sequentially they tried phenylalanine (a precursor of tyrosine) seeing improvement in 95% of the subjects after 6 to 8 months. The theory put forward on why phenylalanine benefits vitiligo patches was that it stops antibodies and allows sun radiation to stimulate melanocytes from other areas to migrate to the damaged ones (Camacho, F. and Mazuecos, J., 1999).

 

50 mg/kg of body weight per day of phenylalanine was administered 1 hour prior to UV A irradiation (twice per week). Of the 19 participants:

i. 5 noted dense re-pigmentation in 6 to 8 months

ii. 13 saw sparse re-pigmentation in the same period

iii. and 1 had no re-pigmentation even after 8 months.

Since the 1980’s there has been no more research examining the benefits of phenylalanine for vitiligo. All 3 studies combining the administration of the amino acid & UVA exposure as well as the 1 that used just the amino acid reported positive outcomes (Szczurko, O. and Boon, H.S., 2008).

 

Vitamin E (Szczurko, O. and Boon, H.S., 2008) and vitamin C have also been shown to support re-pigmentation potentially due to their antioxidant properties.

 

 

Which Genes are responsible for Vitiligo?

NLRP1 is a gene involved in the production of proteins called inflammasomes. Inflammasomes participate in the regulation of the immune system & mutations in NLRP1 have been associated with the presence of autoimmune disorders. The rs6502867 variant of the NLRP1 gene (risky allele: T) was associated with vitiligo in an Indian study (Dwivedi M et al., 2013). Phytonutrient (EGCG) in green tea has been shown to inhibit the action of the NLRP1 gene (Ellis L et al., 2010).

 

Methylation is a process responsible for many functions in the body including cell replication and DNA repair. A study published among 80 individuals (40 with vitiligo & 40 controls) (Yasar, A et al., 2012) showed no correlation between mutations in MTHFR or the levels of serum folate & vitamin B12 among the patients. Had the study measured red blood cell folate and vitamin B12 their findings would have been more significant.

 

Case Studies.

Case 1

The photos in the image above are from a female client in her 50’s. She was following the Wahls dietary protocol for 6 months as an anti-inflammatory / auto-immune friendly approach. The main adjustments in her diet where the increase of fats through nuts & seeds as well as progressing from 2 meals and 1 snack a day to a 16-8 hours fast and then to 1 meal a day (twice per week). Breathing exercises as well as progressive exposure to cold (through showers) were also part of her protocol.

 

References.

Boone, B., Ongenae, K., Van Geel, N., Vernijns, S., De Keyser, S. and Naeyaert, J.M., 2007. Topical pimecrolimus in the treatment of vitiligo. European Journal of Dermatology, 17(1), pp.55-61.

 

Camacho, F. and Mazuecos, J., 1999. Treatment of vitiligo with oral and topical phenylalanine: 6 years of experience. Archives of dermatology, 135(2), pp.216-217.

 

Cormane, R.H., Siddiqui, A.H., Westerhof, W. and Schutgens, R.B.H., 1985. Phenylalanine and UVA light for the treatment of vitiligo. Archives of Dermatological Research, 277(2), pp.126-130.

 

Dwivedi, M., Laddha, N.C., Mansuri, M.S., Marfatia, Y.S. and Begum, R., 2013. Association of NLRP1 genetic variants and mRNA overexpression with generalized vitiligo and disease activity in a Gujarat population. British Journal of Dermatology, 169(5), pp.1114-1125.

 

Ellis, L.Z., Liu, W., Luo, Y., Okamoto, M., Qu, D., Dunn, J.H. and Fujita, M., 2011. Green tea polyphenol epigallocatechin-3-gallate suppresses melanoma growth by inhibiting inflammasome and IL-1β secretion. Biochemical and biophysical research communications, 414(3), pp.551-556.

 

Szczurko, O. and Boon, H.S., 2008. A systematic review of natural health product treatment for vitiligo. BMC dermatology, 8(1), p.2.

 

Yasar, A., Gunduz, K., Onur, E. and Calkan, M., 2012. Serum homocysteine, vitamin B12, folic acid levels and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism in vitiligo. Disease markers, 33(2), pp.85-89.

 

 

How to detect vitamin B12 deficiency

Vitamin B12 is common and unfortunately one cannot rely on serum vitamin B12 to detect a deficiency. Vitamin B12 is carried in the blood by either of 2 proteins: haptocorrin and holotranscobalamin. While the majority of vitamin B12 is carried by haptocorrin, this vitamin B12 is considered inactive* [1]. A serum vitamin B12 test cannot differentiate between the active and inactive form and as a result while the level may appear healthy, the active form of vitamin B12 may be significantly low.

 

Which test is best to identify vitamin B12 deficiency?

The most direct why to detect vitamin B12 deficiency is to measure your active form of B12: holotranscobalamin. Biolab in UK offers that test.

If that test is not available to you, your 2nd best option is to measure your homocysteine levels. Homocysteine is a protein humans synthesise in their body and it’s considered one of the most significant biomarkers of cardiovascular health. Its production relies on the availability of vitamin B12, folate & protein.

source: PMID 16702348 [4]

As multiple other factors though affect the levels of Homocysteine, one cannot drive conclusive results for her vitamin B12 just knowing her homocysteine level.

 

 

Which symptoms indicate vitamin B12 deficiency?

Vitamin B12 plays a critical role in the methylation cycle [3] (which consists of the folate & methionine cycle). As a result any problems associated with methylation may be driven due to:

  1. low vitamin B12 intake (important for vegans and vegetarians)
  2. poor absorption (relevant for those with poor gastrointestinal function) [2] or
  3. compromised metabolism (possibly due to MTR & MTRR polymorphisms)

 

 

 

* due to the fact that haptocorrin receptors are found mainly in the liver.

 

  1. Morkbak, A.L., Poulsen, S.S. and Nexo, E., 2007. Haptocorrin in humans. Clinical Chemical Laboratory Medicine, 45(12), pp.1751-1759.
  2. Schjønsby, H., 1989. Vitamin B12 absorption and malabsorption. Gut, 30(12), p.1686.
  3. Miller, A., Korem, M., Almog, R. and Galboiz, Y., 2005. Vitamin B12, demyelination, remyelination and repair in multiple sclerosis. Journal of the neurological sciences, 233(1), pp.93-97.
  4. Refsum, H., Nurk, E., Smith, A.D., Ueland, P.M., Gjesdal, C.G., Bjelland, I., Tverdal, A., Tell, G.S., Nygård, O. and Vollset, S.E., 2006. The Hordaland Homocysteine Study: a community-based study of homocysteine, its determinants, and associations with disease. The Journal of nutrition, 136(6), pp.1731S-1740S.

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.