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LDN: What Is It & Why It May Help You

Updated: Feb 17

Mast cell activation syndrome (MCAS) is a complex health condition that can cause chronic inflammation and widespread symptoms, including eczema, hives, headaches, migraines, digestive problems, dizziness, weakness, fatigue, and so on. You may have luck improving MCAS by improving your diet, making some lifestyle adjustments, and taking some herbs or supplements. However, if you have a more severe case of MCAS and more complex symptoms, you may benefit from medication along with dietary and lifestyle changes.

Treating complex MCAS can be tricky and, as a functional medicine doctor, I am always looking for new ideas that may help my patients. Emerging research evidence shows that prescribing low-dose naltrexone (LDN) may benefit patients with MCAS. Today, I want to talk about LDN: what it is and why it may help you if you are dealing with mast cell activation.

What Are Mast Cells?

Your mast cells play a critical role in your immune system and overall health. They are a type of white blood cells in connective tissues, including your digestive tract, skin, respiratory tract, urinary tract, reproductive organs, surrounding your nerves, and near your blood vessels and lymph vessels. Your mast cells are in charge of storing histamine and other inflammatory mast cell mediators. When your body encounters an allergen or is exposed to a foreign pathogen or chemical, it can release these inflammatory mediators to fight invaders and protect your body.

What Is Mast Cell Activation Syndrome?

Though your mast cells are absolutely necessary for your health, you don’t want too much of the good thing. Overactive mast cells can increase your risk of mast cell disorders, including mast cell activation syndrome (MCAS). MCAS is a complex health condition that can cause chronic inflammation and widespread symptoms (1, 2, 3, 4).

Symptoms of Mast Cell Activation Syndrome

Symptoms of MCAS may vary from person to person. You may only experience a couple of symptoms or you may have widespread symptoms affecting several areas or your entire body. Your symptoms may be anywhere from mild to severe.

Your symptoms of MCAS may include:

  • Rashes, eczema, and other skin issues

  • Hives

  • Itching

  • Low blood pressure

  • Heart palpitations

  • Chest pain

  • Headaches of migraines

  • Fatigue

  • Brain fog

  • Weakness

  • Dizziness

  • Loss of appetite or low appetite

  • Rapid weight loss or weight gain

  • Rhinitis

  • Gastrointestinal troubles, including abdominal pain, diarrhea, nausea, and vomiting

  • Nervous system symptoms, such as anxiety

  • Vision changes

Triggers of Mast Cell Activation

Mast cell activation may be triggered by a variety of factors, including:

  • Mold

  • Allergens, including insect bites, gluten, other foods, and preservatives

  • Infections, including viruses and fungi

  • Chemicals and other toxins, including conventional cleaning and personal hygiene products

  • Heavy metals, including mercury from dental work

  • Smells, including perfumes and other conventional beauty or body products

  • Medications, including antibiotics, ibuprofen, and opiate pain relievers

  • Physical or psychological stress from anxiety, exercise, lack of sleep, pain, rapid temperature changes, or other factors

  • Hormonal changes, including hormonal fluctuations during the menstrual cycle

  • Mast cell hyperplasia, a rare health condition related to certain chronic infections or cancers

LDN and Its Potential Use for MCAS

If you’ve been following my work, you know that I’ve written about natural treatment options for MCAS. You can read my tips for stabilizing mast cells here. You may be able to improve your health by finding and avoiding your triggers, improving your diet, making some lifestyle adjustments, and taking some herbs or supplements.

MCAS, however, is a complex health issue. If you are dealing with a more aggressive form of MCAS or more stubborn symptoms, you may benefit from taking medication along with making nutritional and lifestyle adjustments.

New, emerging research evidence shows that prescribing low-dose naltrexone (LDN) may benefit patients with MCAS.

Naltrexone was originally designed and approved for preventing relapse in alcoholics and those addicted to narcotics. It acts as an opiate antagonist. This means that naltrexone competes for the same opiate and endorphins receptors that opioid drugs and alcohol do. As a result, when patients take naltrexone, they will feel less “high” from opioids or alcohol. This may reduce cravings and may aid recovery.

But how can a medication developed for addictions help someone with MCAS? A lot it seems. It is not unusual in medicine to find a medication that was originally developed for one thing but may help other health issues as well, and sometimes at a different dose. This is what happened with naltrexone. According to a 2011 article published in Experimental Biology and Medicine, researchers at The Pennsylvania State University College of Medicine have discovered that used off-label, low dose naltrexone (LDN) may help to support the treatment of various autoimmune diseases and cancer by having an inhibitory effect on cell proliferation (5). Researchers found that LDN increases the production of your body’s natural endogenous opioids causing inhibition of cell proliferation. As a result, LDN may help to reduce pain levels and improve overall health in patients with autoimmune disorders and cancer (6, 7, 8).

LDN may also trick your opiate and endorphin receptors to increase endorphin production. The release of these ‘feel good’ chemicals may also make patients feel better (9). Binding to opiate receptors, LDN may also have an immunoregulatory effect when prescribed between 0.5 and 4.5 mg. A surge of endorphins may stimulate your immune system and elevate T-lymphocyte levels (10, 11). An increase of T-lymphocytes can decrease inflammatory cytokine and antibody production, which may help to decrease symptoms and improve balance within your body (12).

Moreover, research has shown that LDN may also offer anti-inflammatory benefits for various health issues. A 2009 clinical trial published in Pain Medicine has found that LDN may help to improve inflammation and symptoms in fibromyalgia (13). When your body encounters an infection or other trigger of inflammation, it can lead to an increased expression of toll-like receptor (TLR), TLR-4. TLRs are part of your body’s security system. When they note a foreign intruder, they will alert and activate your mast cells to fight the invaders. An increase in TLR-4 will increase pro-inflammatory cytokine production. However, according to a 2008 study published in the European Journal of Neuroscience, LDN is a TLR-4 antagonist (14). Thus, it can help to reduce inflammation and related symptoms.

According to a 2017 10-week pilot study published in Biomedicines, LDN may be beneficial for fibromyalgia patients (15). In this relatively small study, 8 female participants with fibromyalgia were prescribed 4.5 mg of LDN taken every night for the duration of the study. Researchers noted a significant reduction in their pro-inflammatory cytokine levels and tumor necrosis (TNF)-ɑ levels. They also noted a 15% decrease in fibromyalgia pain and an 18% decrease in overall symptoms.

A 2020 study published in the International Journal of Pharmaceutical Compounding has looked at the benefits of LDN for psoriasis (16). Researchers found that LDN may help to reduce cytokine production, regulate lymphocyte response, and decrease mast cell activity. It seems that LDN helps to reduce mast cell activity and as a result reduces inflammation and symptoms in various health issues. This suggests that it may also be helpful for some patients with MCAS.

MCAS is a complex condition characterized by inflammation and an array of symptoms. There is still limited research on the potential benefits of LDN for MCAS. However, what we know is promising. A 2018 case report published in BMJ Case Reports has found that LDN and intravenous immunoglobulin (IVIg) therapy had led to a significant improvement of neuroinflammatory pain and symptoms in severe MCAS and post orthostatic tachycardia syndrome (POTS) (17). According to the author, this may be a result of LDN blocking the TLRs that trigger mast cell activation. The author reported success using LDN and antibiotics for other patients with MCAS.

Can LDN Treat MCAS?

We need more research evidence to fully understand the potential benefits of LDN for MCAS. However, current evidence suggests that LDN has the potential to treat MCAS and other conditions.

LDN is still considered experimental and off-label. However, progressive doctors who are aware of all the existing research-based evidence may still prescribe it for patients who have not achieved success using only standard treatments and natural strategies for MCAS.

The typical dose of LDN is 1.5 to 4.5 mg of a compounded immediate-release tablet, generally taken at bedtime. As with every medication, it’s critical that you work with your doctor and take it as directed. Do not start taking LDN or any other medication or supplement without consulting with your doctor. MCAS is a complex health issue and it’s important that we find the right diet, lifestyle choice, supplements, and potentially, medications to stabilize your mast cells and bring back homeostasis to your immune system.

Next Steps

Are you experiencing symptoms of MCAS? Are you interested in what treatment options are best for your situation? Working with a healthcare practitioner knowledgeable about histamine intolerance and MCAS is the best way to get to the root cause of your symptoms and create an individualized treatment. I welcome you to start a personalized functional medicine consultation with me for further guidance to improve your health. You may book your consultation here. Check out my Histamine Intolerance Course here. Learn on your own time, from anywhere. Get an inside look at the most helpful functional medicine tests for pinpointing imbalances, ways to identify and manage the most common (and sometimes surprising) mast cell triggers, and learn what to eat, what to avoid, and why.


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