Histamine and serotonin in the PMDD picture - Is it a real allergy????

Histamine and serotonin in the PMDD picture

Have you ever tried antihistamines for PMDD?

Did they work????

If they do provide you with some relief, then the below info is an explanation of why they work.

Estrogen (in excess compared to progesterone, in a estrogen dominant state) turns on both the multiplication of mast cells, and their tendency to release histamine and serotonin. This is a vicious cycle because each drives the next in an upward negative feedback loop, especially if the cycle is not broken. here's where your antihistamines come in. 

In his article titled, "Serotonin, depression, and aggression:  The problem of brain energy", Dr Ray Peat PhD addresses the link between all 3 compounds:

"Serotonin and estrogen have many systematically interrelated functions, and women are much more likely to suffer from depression than men are. Serotonin and histamine are increased by estrogen, and their activation mimics the effects of estrogen. Serotonin is closely involved in mood disorders, but also in a great variety of other problems that affect women much more frequently than men. These are probably primarily energy disorders, relating to cellular respiration and thyroid function. Liver disease and brain disease, e.g., Alzheimer’s disease, are both much more common in women than in men, and serotonin and estrogen strongly affect the energetic processes in these organs. Liver disease can increase the brain’s exposure to serotonin, ammonia, and histamine. It isn’t just a coincidence that these three amines occur together and are neurotoxic; they are all stress-related substances, with natural roles in signaling and regulation."

Interesting he mentions liver disease... many ageing women also suffer NAFL nowadays because we have more, and more compromised livers.

Histamine is broken down in the body by an enzyme called Diamine Oxidase (DAO). If you develop a DAO deficiency and are unable to break down histamine, you could develop an intolerance—which is where all the symptoms come in, which in turn affects PMDD. Some of these include: headaches bloating, abdominal pain, nausea, flushing, especially of the head and chest, a congested, runny, or itchy nose red, itchy, or watery eyes, dizziness, heart palpitations. 

Do these symptoms sound familiar???

Yep, partially the symptoms of the syndrome many experience with PMDD.

Some reasons your DAO enzyme levels could be affected include: medications that block DAO functions, or prevent production, gastrointestinal disorders, such as Leaky Gut and IBS (also linked to... surprise, surprise... an over production of serotonin in the gut). 

Histamine-rich foods that cause DAO enzymes to function improperly, foods that block DAO enzymes, or trigger histamine release. 

Bacterial overgrowth is another contributing factor for developing a histamine intolerance. Bacteria grows when food isn’t digested properly, causing histamine overproduction. Normal levels of DAO enzymes can’t break down the increased levels of histamine in your body, causing a reaction.

Dr. Peat advised: “And one of the things that turns on the production of more mast cells, or the secretion, or leakage of histamine from the mast cells is prostaglandins produced from polyunsaturated fatty acids, especially prostaglandin E2*. Besides making the prostaglandins in themselves, they cause changes in cells that disrupt their functions. In fact, every function of the cell can be disrupted by too much of the polyunsaturated fats. And one of the worst things they do is to interrupt oxidative metabolism and the energy deficit, I think it's ultimately the thing that leads to really serious allergy problems.”  

Things that help Diamine Oxidase production & therefore histamine intolerance …T3, Vitamin E, Magnesium, Vitamin C, Calcium & Vitamin K, Vitamin D, Copper, Progesterone. Less protein (as undigested protein in the gut raises histamine. Or you can improve your digestion). 

On Histamine, Dr. Peat advises…“T3, the active form of thyroid hormone… does several things that prevent overproduction of histamine. It’s been known as an anti-inflammatory for a long time, but one of its mechanisms is to stabilise mast cells so they don’t secrete serotonin, histamine and other inflammatory things.”

“Yes, the calcium and vitamin D are two of the things that are very strongly anti-allergic. Magnesium is the most famous because of magnesium deficiency, they found caused terrific range of inflammatory diseases in animals and they would cure skin diseases, heart disease, nerve disease, liver disease and so on just by correcting a magnesium deficiency. With vitamin D and calcium working with magnesium are very important so that some people cure their allergies just by supplementing vitamin D or vitamin K which is the other major calcium regulating vitamin.”

“…the real thing I think is to adjust your thyroid and progesterone. Progesterone has broad variety of antihistamine effects. Estrogen turns on both the multiplication of mast cells and their tendency to release histamine and serotonin. And so getting your thyroid to a good level will reduce your estrogen and increase your progesterone, and shift the balance in histamine production. Aspirin is another antihistamine that works indirectly by reducing prostaglandin production and nitric oxide production.”

*Prostaglandin E2 (PGE2) plays different roles through the inflammation and resolution cycle, acting in both proinflammatory and anti-inflammatory capacities. Dysregulated PGE2 production and signaling has been implicated in the progression and chronic nature of certain autoimmune diseases.

So, this is why certain antihistamines work for PMDD - especially ones that also have anti-serotonin properties like Benadryl, phenergan, or cyproheptadine. Many cite this positive account of antihistamines as being evidence that PMDD is an allergy to your own hormones, but don't go far enough in pinpointing which one (estrogen), and its effects on the rest of the balance we rely on. As pointed out, Dr. Peat mentions that progesterone is a natural anti-histamine. 

Considering that PMDD symptoms are worse in the luteal phase, many also blame progesterone for PMDD when its likely that the overproduction of histamine, serotonin and estrogen in the luteal phase is one of the root causes instead, coupled with a natural progesterone deficiency. 

Moving forward, long term anti-histamine use isn't advised... It's merely a bandaid to give you a clue to what you really need to deal with. Better instead to work on lowering estrogen, prostaglandins, serotonin and histamine with improving gut health (getting rid of endotoxins), supporting your thyroid, eating nutrient dense food such as organ meats that contain DAO and other pro-metabolic foods including the removal of PUFA from the diet, and balancing estrogen and progesterone ratios (potentially with progesterone therapy).

It all sounds so easy, doesn't it??