- Posted by DanTomas
Topics discussed: the physiological root cause of chronic hives & migraines / hives treatment / migraine treatment
What you need to know
Hives (urticaria) is a skin rash consisting of inflamed and often itchy welts. Now there is a lot of confusion about chronic (persistent) urticaria because medical science in this area is in its infancy. It’s not life threatening and therefore will not attract much research funding, but that doesn’t mean it isn’t causing stress, sleep deprivation, and anxiety that can severely impact our quality of life. You need answers, but chances are that your doctor has diagnosed you with chronic idiopathic urticaria, which is med-speak for ‘I have no idea, but take these antihistamine pills and don’t let the door hit your ass on the way out’. The internet is populated with the typical data dump, an endless stream of information. You have probably gathered by now that understanding hives is like solving a gigantic jigsaw puzzle by finding those gems of insight in a bottomless abyss of content.
Migraines are a related condition as we shall see. The international headache society describes them as ‘transient and localized stabs of pain in the head that occur spontaneously in the absence of organic disease of underlying structures or of the cranial nerves’. Again they will be diagnosed as idiopathic, a term meaning your doctors cannot identify your root problem.
I have spent years researching this subject within the context of gerontology by looking at the latest research and biohacking my way to peak fitness. I have seen off two periods of chronic hives in the last 15 years. My aim here is to create the most definitive guide on the Internet to identifying the root cause of spontaneous hives and migraines. It will provide you with the tools and protocol to live symptom-free. I want to be upfront that you are looking at approximately 6 months to allow your body to sufficiently adapt and heal. There is no quick fix and your predisposition will not disappear. The good news that you can recover from these conditions at very little cost and your persistence will pay off. If a reoccurrence happens in future you will understand why and you will be able to minimise your downtime.
This guide will delve into some biochemistry only to explain key points. I have translated the relevant information into plain English from the tech-waffle as much as possible. Bear with me.
It is important to follow all the steps as religiously as possible because hives and migraines are the results of several problems. Your feedback is valuable so if you follow this protocol then please write in with your results around the 6 month mark.
The story starts with histamine which is a naturally occurring bioactive compound that has wide-ranging functions in the body from blood pressure regulation to acting as a neurotransmitter. However, its role as a vasodilator in our immune response is often implicated (partially correct) as the cause of hives and migraines. Histamine originates from mast and basophils cells (types of white blood cell). When antibodies (specialised proteins) detect foreign pathogens like bacteria and viruses they release histamine. This increases permeability of capillaries (blood vessels) to allow white blood cells to enter infected tissue and fight the detected pathogen.
The problem is that when too much histamine is produced, excessive permeability opens the floodgates for blood plasma to leak from capillaries into surrounding skin tissue. The result is insufferable migraines and/or welts cascading across your body and/or ice pick headaches.
Now here is where the diagnosis typically goes wrong. We start with an assumption that our immune system must have been triggered because we are producing histamine, therefore we must have suddenly become allergic to something. This leads to a frantic search for a mystery allergen. In some cases this assumption proves correct, you identify the allergen and eliminate it from your diet. Job done. However in idiopathic urticaria/hives and migraines, there is no allergen, what you have is histamine intolerance.
Chronic idiopathic urticaria or migraines = Histaminosis (Histamine intolerance)
Histamine has another major function in the body which is as a component of gastric acid and used to break down food. Histamine is produced by enterochromaffin-like cells in the gut to modulate stomach acid secretion. The point is that histamine is produced by our bodies independently of an immune response. This is also why you may find that binge drinking or vomiting will trigger gut-histamine release and a hives reaction (more on that later). Additionally, other major pathways to elevated histamine levels are:
- High histamine foods
- Diamine Oxidase (DAO) deficiency
- Yeast overgrowth and SIBO (Small intestinal bacterial overgrowth)
- Inflammatory bowel diseases
There are arguably other factors but it is important in the first instance to focus on getting the bulk of excess histamine out of your system as fast as possible. You can then fine tune your strategy later. I have seen far too many experts get caught up in the intricacies of histamine release which have minute effect. It is important to strategically target the biggest culprits of histamine release to be of practical value.
Natural blood plasma levels of histamine are between 0.3 to 1.0 nanograms per millilitre (ng/mL). Low levels of histamine being released and absorbed by mast cells is perfectly normal. The class of biogenic amines to which histamine belongs can be found in all living organisms and therefore are present in foods like milk, fish, fruit and vegetables. However, we all have a tolerance threshold, and exceeding this level will result in symptoms such as hives, migraines and heart palpitations to name but a few. But why exactly does eating standard food products cause elevated histamine in some people and not others?
The enzyme responsible for the metabolism and elimination of ingested histamine is Diamine Oxidase (DAO). Its activity can be reduced significantly due to drug interactions, changes in gut flora, or genetic reasons. Unless you have suffered hives and migraines ever since you were born it is likely you do not have any significant genetic problem preventing full recovery. So now we can start to home-in on DAO activity.
The fact that DAO is largely formed in the intestinal mucosa tells us that idiopathic hives and migraines are likely a disease of intestinal origin. Damage to the cells that produce DAO will result in insufficient metabolism of ingested histamine. DAO is also produced by the kidneys, and interestingly, by the placenta. During pregnancy it is known that DAO levels are between 500 to 1000 times normal which is why expectant mothers will find their hives disappears, and return after birth.
Step 1. Up your intake of co-factors that lead to DAO production; these are vitamin C, vitamin B6, and copper.
Copper deficiency is very rare due to its ubiquity in standard diets and therefore supplementations is not recommended unless a blood test reveals you are in fact deficient.
There is evidence that alcohol and acetaldehyde (a metabolite of alcohol) liberates histamine from gastric mucosa in the stomach, and from mast cells in soft tissue. It gets worse. Alcohol and histamine are broken down by the same enzymes so when both are present in excess they can easily overwhelm your capacity to eliminate them. Further, histamine levels are elevated by the process of fermentation which means that non-distilled alcohols such as beer and wine are naturally very high in histamine.
Alcohol is absorbed slowly from the stomach and very rapidly in the small intestine where there is a much larger area for absorption. When alcohol is consumed on an empty stomach, histamine is liberated, and gastric emptying into the small intestine happens faster. A large amount of both alcohol and histamine is now in your bloodstream! Now you can probably figure out the preventative measure which is never to drink on an empty stomach. A more effective thing to do is to pre-load by eating a high-fat or high protein food which will significantly slow gastric emptying. However not all fats seem to have this effect, some studies have found that olive oil is superior to other oils for expediting GE; something to bear in mind.
Vomiting (especially alcohol induced) is another mechanism for massive histamine release because as it rapidly diffuses through the mucous membrane under the tongue. This is a more direct route into your bloodstream and bypasses the DAO produced in the stomach. This is the reason why many pharmaceutical drugs are designed for sublingual administration.
Bottom line. The interaction between alcohol and histamine creates a perfect storm which can easily pass your tolerance threshold especially in histamine intolerant people.
Step 2. Cut out alcohol entirely for one month to let your DAO levels recover
N.B If you do drink, try to stick to spirits and mixers which have lower histamine content than beers, wines, and champagnes. Ensure you eat before drinking. I appreciate it is not easy to change drinking habits, however think of this as a temporary tactic, you can always consider reintroducing your old drink of choice when you can cope. As always learn to listen to your body.
Gluten, Gliadins, and Zonulin overproduction
So we have established that histamine is produced in the gut and levels can rise too high due to lack of DAO. But there is another factor pushing histamine levels up which is the consumption of foods that cause increased permeability of the intestinal tract. Zonulin is an inflammatory protein discovered only in 2000 and is known to modulate intestinal tract permeability. Now excessive permeability is a cascading disaster. It opens the floodgates to ingested histamine, histamine produced in the gut, pathogens, and undigested food particles. Pathogens and undigested food particles in turn trigger further histamine release from mast cells. Therefore we must keep Zonulin in check. Action to take is to reduce consumption of Gliadins which are glycoproteins present in gluten containing foods. Glaidin activates zonulin production in all people irrespective of their genetics.
Step 3. Eliminate all gluten found in the cereals wheat, rye, and barley. Make rice your staple carbohydrate and vary it with potato based dishes
Vitamin D is referred to as the sunshine vitamin because it is produced by our skin in response to sunlight in the UVB spectrum. A deficiency affects almost 50% of the global population to some degree. Let that statistic sink in. This is nothing less than a pandemic and the blame is attributed to the massive discrepancy between typical urban conditions vis-à-vis the conditions we are evolutionarily adapted to. A modern lifestyle typically means living, working, and socialising indoors. We are increasingly migrating to cities where we commute underground. Now consider the war on sun exposure from people worried about cosmetic ageing effects. The result is we get a fraction of the direct sun exposure we need to produce vitamin D.
The relationship between migraines, hives, and vitamin D is that decreased serum levels have been shown to have a significant association with dysregulated immune function. Mast cells express the vitamin D receptor (VDR) and produce metabolites that supress pro-inflammatory and vasodilatory mediator production. Researchers have also found that topically applied vitamin D3 significantly reduces the magnitude of passive cutaneous anaphylaxis (a hives outbreak).
Advice on dietary changes is misleading. The Vitamin D Council have said getting the right amount of Vitamin D does not depend on your diet because these quantities are inadequate to meet healthy serum levels. The ideal solution is to increase your daily sun exposure, any increase is good, however this is not a possibility for many millions of us that do not have the opportunity to work under the sun. The answer is to supplement in the D3 form (cholecalciferol) at the optimum strength of 5000ui, and in dry tablet form.
Vitamins work synergistically with other vitamins and minerals, these are cofactors. With respect to vitamin D3, the cofactors are Magnesium, Zinc, Vitamin K, Boron, and Vitamin A. Magnesium is the only cofactor of D3 that requires routine supplementation. Mg is an essential mineral vital for many physiological pathways and is a cofactor of hundreds of enzymes. The problem is absorption requires high intake levels that are absent on a standard diet. Furthermore Mg is depleted easily in your body from carrying excess fat, sweating from exercise, and consuming alcohol, caffeine and salt. Magnesium is the second most abundant mineral inside our cells and the second most common deficiency after Vitamin D.
Aside from being a vitamin D cofactor, magnesium deficiency is known to trigger mast cell proliferation. More concerning still is that mast cells developed during magnesium depletion are defective in storing and secreting histamine. Magnesium deficiency alone could be the root cause of migraines and hives. Bottom line is that supplementing with 500mg/day will reduce the histamine in your system and increase DAO levels.
Elemental magnesium must be bonded as a salt of which there are a range available. The cheapest and most ubiquitous is Magnesium Oxide however its bioavailability is as low as 4%, which is the amount of elemental magnesium the gut can absorb. The form with the best bioavailability to cost profile is magnesium citrate at 16%. The right amount to correct a deficiency and suitable for ongoing use is 400mg/day, supplementation above 500mg is not harmful but can cause a laxative effect in some people and provides no additional benefit.
Step 4. Supplement with 5000ui of vitamin D3 and 400mg Magnesium
Water purification for controlling hives and migraines
Everyone needs a water strategy!
Drinking water standards in the US are set by the Safe Drinking Water Act (SDWA) and determines maximum contamination levels for physical, chemical, and biological contaminants. In the EU there is the Drinking water quality directive which set EU levels. There are several chemical disinfectant methods to lower biological contaminants, however these processes all introduce levels of disinfectant contaminants such as chlorination-by-products (CBP) and/or nitrification. The take home point is that there is always a trade-off between the dangers of physical, biological contaminants, and disinfectant by products. You are never getting pure water directly from the tap.
Now it is a difficult regulatory balancing act to decide on maximum contamination levels and indeed regulations are adapted from time to time and differ from country to country. Although the EU has standardised maximum contamination levels, different disinfectant methods are practised in different territories. For example France uses mainly ozone, whereas Italy and Germany use an ozone or chlorine dioxide process. The UK and parts of Spain use chloramines for residual disinfection in their distribution network, whereas this process is prohibited in France. Generally in central Europe (Berlin, Amsterdam, Zurich, and Vienna) there is no distribution-system residual. This may well be a root causal factor for the common phenomena of drastic health changes after relocation. If you have experienced this please write in.
We must appreciate that it is a marvel of modern engineering that we have water out of the tap that is even remotely drinkable. What is considered safe and technically achievable at a given cost by regulators is relative. Their goal is to produce water that is drinkable for mass populations in the long term, whereas our goal is to access pure water for peak health.
The reality is that contaminants cause premature ageing and sensitivities that impact over the course of decades. Drinking pure water is the first place to start with any health improvement strategy. Some people believe that pure water is not ideal because it is too pure, the theory being that drinking pure water will leech minerals like calcium from your body. This makes no sense because unless you are fasting for days on end or are trekking through Death Valley and sweating out all your electrolytes then you are getting all your mineral nutrition from food. What you should be getting from water is pure H2O as far as practically possible. So what does a good water strategy look like? The answer depends on your long-term living plans.
Step 5. Choose a water purification system and make drinking clean water a permanent lifestyle choice, you won’t look back
High histamine foods, histamine liberators, and DAO blockers
Some foods are notorious for containing high levels of histamine. Eliminate all high-histamine foods as listed below until all sign of hives disappears which means your histamine is under control. At this point you can consider reintroducing some of the foods you enjoy in moderation, so we are not advocating an impossibly strict diet. It is not the food per se, but rather bacteria that in the food that produce histamine. Therefore aged or fermented foods will be targeted in the initial phase of our strategy.
Citrus fruits are complicated with respect to histamine. They are an example of foods that are known to release endogenous histamine, that is they liberate histamine from your mast cells. In fact, I experienced a full blown outbreak after drinking a glass of orange juice. It is important to realise the distinction between citrus and ascorbic acid (vitamin C), which as mentioned earlier is a cofactor of DAO. Vitamin C significantly increases your DAO reserve and therefore lowers serum histamine (as well as having a plethora of beneficial effects throughout the body). We know there is an association between citrus fruit and histamine release but it is unclear exactly how this happens. More work needs to be done to identify the metabolic pathway.
The general rule here is to avoid citrus fruits and supplement with a dose of vitamin C not greater than 500mg twice a day. If you are experiencing a migraine or hives attack do not eat any citrus fruit. Wait until your DAO has processed the histamine and you are relatively symptom-free before ingesting small amounts of citrus. Citrus is not bad per-se however an awareness of timing and moderation will keep histamine below your tolerance threshold.
Tea and coffee
The effect of caffeine on histamine release has been investigated in rats, the findings were that caffeine has the capacity of blocking the release of both histamine and DAO. Therefore the result of drinking caffeine will depend on how much DAO and histamine your body is producing. Assess how your body reacts, but as a general rule most people drinking up to 4 cups of tea or coffee a day will get all the upsides without any downside.
I have seen many publications recommending supplementing with a green tea polyphenol called Epigallocatechin gallate (EGCG) due to its ability to inhibit histidine decarboxylase (HDC). The rationale is that HDC is responsible for catalyzing histamine from histidine, and therefore taking EGCG will result in lower histamine. This is very unfortunate advice. EGCG is a highly-concentrated extract that places a heavy strain on your liver, and liver toxicity is a known problem. The best way to benefit from tea is to drink tea, in moderation, preferably in the green or white variety.
Step 6. The food and drink protocol
Eliminate for 3 months, moderate after:
- mature cheeses
- Fish and shellfish
- non-distilled alcohol
- cured meats
- yeast products
- pickled, preserved or fermented products (kimchi, sauerkraut, yoghurt, kefir, kombucha)
- Ready made meals
Moderate your intake of histamine liberating foods:
- Citrus fruits (and juices), chocolate, nuts, beans and pulses, tomatoes, food additives and food dyes.
Moderate your intake of these Diamine Oxidase (DAO) blockers:
- Alcohol, Tea (Green, black, or white), Energy drinks, Mate tea
The problem with antihistamines and DAO supplements
You may be wondering why antihistamines and DAO (diamine oxidase) supplements are not included in this protocol. The reason is that neither of these treats the root cause of histaminosis. Antihistamines for example do not reduce histamine at all, rather it blocks the effect of histamine. DAO is a new and far superior product, yet it does not help you produce DAO naturally which is what should happen in a healthy state. Now with that said, there is a good argument for using DAO supplementation for emergency relief. As it will take a matter of months to recover using the long-term metabolic and psychosomatic protocols, it makes sense to use DAO pills strategically so that you gain a sense of normality in the meantime. If antihistamines provide you temporary relief then take them with caution.
Read part 2, the psychosomatic protocol
Read part 3, an addendum on emergency relief
If you have been following this protocol then I would be interested in hearing your results in the comments below.
Alcohol-histamine interactions https://www.ncbi.nlm.nih.gov/pubmed/10344773
Effects of lipase inhibition on gastric emptying and alcohol absorption in healthy subjects https://www.ncbi.nlm.nih.gov/pubmed/17092377
Effects of histamine and diamine oxidase activities on pregnancy: a critical review https://www.ncbi.nlm.nih.gov/pubmed/18499706
Impact of oral vitamin C on histamine levels and seasickness https://www.ncbi.nlm.nih.gov/pubmed/25095772
The role of vitamins B3 and vitamin C in treating Histadelia http://orthomolecular.org/library/jom/2002/pdf/2002-v17n01-p017.pdf
Determining the correct vitamin D3 dosage https://www.vitamindcouncil.org/why-does-the-vitamin-d-council-recommend-5000-iuday/
Determining the correct B6 form and dosage https://www.westonaprice.org/health-topics/abcs-of-nutrition/vitamin-b6-the-under-appreciated-vitamin/
Risks of EGCG https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189735/
Newman, Lawrence C., MD. “Effective Management of Ice Pick Pains, SUNCT, and Episodic and Chronic Paroxysmal Hemicrania.“ Current Pain and Headache Reports 2001, 5:292–299.
Vitamin D3 and Chronic Hives. Rasool R., et al. Chronic urticaria merits serum vitamin D evaluation and supplementation; a randomized case control study. World Allergy Organization Journal, 2015.
Catalytic role of copper in production of DAO https://www.ncbi.nlm.nih.gov/books/NBK222312/
Vitamin D Supplements Improve Urticaria Symptoms and Quality of Life in Chronic Spontaneous Urticaria Patients https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203568/
Vitamin D3 represses IgE-dependent mast cell activation via mast cell-CYP27B1 and -vitamin D receptor activity https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4154631/
Role of Cellular Magnesium in Human Diseases https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4379450/
The Definitive Guide To Magnesium & Magnesium Supplements http://www.metabolics.com/blog/the-definitive-guide-to-magnesium-and-magnesium-supplements/
The Importance of Body Weight for the Dose Response Relationship of Oral Vitamin D Supplementation and Serum 25-Hydroxyvitamin D in Healthy Volunteers https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220998/
Did you like this guide on chronic hives and migraines? If so please help us out by liking and sharing