Mast Cell Issues? Why You Want to Lose Weight

by | Nov 7, 2022 | Blog, General Wellness | 0 comments

Obesity is a serious epidemic in Canada, the United States, and most of the world. It is a major contributing factor to chronic health conditions, including high cholesterol, high blood pressure, type 2 diabetes, and heart disease (and has been a major risk factor for severe COVID).  

Preventing obesity and maintaining a healthy weight is critical for reducing inflammation and the risk of chronic health issues. It’s also critical if you have mast cell issues.

In this article, I want to discuss the connection between obesity, weight gain, and mast cells. You will learn about the link between weight gain and mast cells. I will also discuss how obesity can drive inflammation and increase the risk of inflammatory conditions. Finally, I will share my best tips for weight loss. Let’s get into it and discuss why you may want to lose weight if you have mast cell issues.

What Are Mast Cells

Your mast cells play a critical role in your immune and overall health. They 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.

Your mast cells are essential for your overall health. However, overactive mast cells can cause issues. They may lead to mast cell activation syndrome (MCAS) or other mast cell disorders.

MCAS is a complex health condition that can cause chronic inflammation and widespread symptoms, including skin issues, headaches, migraines, fatigue, brain fog, weakness, dizziness, gastrointestinal troubles, anxiety, rhinitis, and more (1, 2, 3, 4). There may also be a connection between obesity, weight gain, and mast cell problems. I will get into this connection in the next section.

Weight Gain and Mast Cells

Weight gain, obesity, and difficulty losing weight are common problems for people like you, who struggle with mast cell activation issues. But why? What’s the connection between weight gain and mast cells?

Inflammatory Molecules

One of the main reasons behind weight gain and mast cell issues is the constant inflammation that can be triggered by your mast cells. You see, mast cell activation and inflammation are a very beneficial thing when you have an acute infection, illness, or injury. Your body can protect you and support healing through inflammation. However, when you are experiencing mast cell activation issues and chronic inflammation, these can cause chronic health issues, weight gain, and obesity. 

Certain inflammatory molecules released by your mast cells, including interleukin-6 (IL-6) and tumor necrosis factor (TNF), have been linked to obesity. A 2009 review published in Inflammatory Research has found that IL-6 secretion may affect various metabolic factors, including “adipose tissue-specific gene expression, triglyceride release, lipoprotein lipase downregulation, and insulin sensitivity” (5). A 2019 study published in Cancer (Basel) has also found that TNF and IL-6 signaling may be a link between inflammation and obesity (6). Testing IL-6 levels is also used for diagnosing both chronic inflammation and mast cell issues. 


Besides IL-6 and TNF release, leptin may also play a role in weight gain and obesity in mast cell disorders. Leptin is a hormone that’s released by your mast cells. People with mast cell activation problems often have higher levels of leptin. In others, leptin doesn’t work as it should, forcing the body to make more (7, 8, 9).

Leptin helps to regulate your appetite. It helps to balance your food intake and energy use. But if you have unusually high levels of leptin or leptin resistance, it can lead to weight gain and obesity (10). At normal levels, leptin lets your body know when you don’t require more food. High levels of leptin can lead to an aversion to the hormone. This is known as leptin resistance. Leptin resistance means that your body is not getting the needed feedback about when to stop eating, so you may want to keep eating even when your body is full.

Increased weight, or rather, more fat, may also mean more mast cells. Your mast cells live in your adipose or fat tissue, as a second reservoir in addition to your bone marrow. Leptin helps to control how many mast cells are located in your adipose tissue. Leptin may also urge your mast cells to make more TNF, IL-6, and other inflammatory molecules. This will lead to more inflammation and more weight gain.

Moreover, leptin works in the opposite way of another hunger hormone, ghrelin. Ghrelin is another hormone that plays a role in your appetite and weight. It tells your brain when you are hungry, but it also tells your cells to stop making and releasing inflammatory molecules. If your leptin levels are too high, but you don’t have enough ghrelin to compensate and tell your body to reduce inflammation, it can lead to further inflammation and weight gain (11).


Certain medications used for mast cell activation issues may also explain the connection between weight gain and mast cells. In some cases, addressing mast cell activation problems with medication may actually reduce related weight gain. According to a 2012 study published in Diabetes/Metabolism Research and Review, addressing stabilizing mast cells with anti-allergy drugs, cromolyn and ketotifen (Zaditor) may help to prevent or reduce obesity and diabetes (12). However, in others, mast cell medications may cause weight gain. This can be frustrating, as I’ve seen in clinical practice.

Increased appetite and weight gain are among the common side effects of some H1 antihistamines, including cetirizine, fexofenadine, and desloratadine, used for mast cell problems (13). Steroids for mast cell issues, including prednisone and methylprednisolone, can also lead to weight gain and swelling (14). 

Lifestyle Factors

Lifestyle factors may also play a role in obesity, weight gain, and mast cell disease. If you have mast cell activation issues, you may have a difficult time getting enough restful sleep. Your mast cells tend to be highly active at night, which may cause insomnia and sleep problems (15). Not sleeping enough or well can increase chronic inflammation and chronic stress and may contribute to weight gain (16).

Some people with mast cell activation issues may also find exercise exhausting. You may even experience exercise intolerance. According to a 2019 study published in the Journal of Allergy and Clinical Immunology, exercise may increase histamine levels and symptoms in those with mastocytosis (17). Not moving your body enough may contribute to weight gain or hinder weight loss.

Lastly, if you have mast cell activation issues, you may be facing dietary restrictions. Many patients remove foods that are triggering but may not pay enough attention to the rest of their diet. Safe foods may not always be healthy and may increase weight gain. Unless you know how to follow a low-histamine, anti-inflammatory, and nutrient-dense diet without triggers, you may be consuming unhealthy foods that increase inflammation and contribute to weight gain.

The Problem with Obesity

Chronic inflammation in the body can increase the risk of weight gain, and obesity can increase the risk of inflammation. This can lead to a vicious cycle of obesity and inflammation. Obesity is a major risk factor for many diseases, including asthma, diabetes, inflammatory bowel diseases (IBDs), rheumatoid arthritis, autoimmune diseases, neurodegenerative diseases, heart disease, cancer, and more. 

Chronic inflammation can also affect your body’s insulin response. According to a 2018 study published in the Journal of Clinical Investigation, insulin resistance can promote body-fat inflammation (20). It seems that obesity may induce insulin resistance which then promotes chronic inflammation.

Thyroid problems, hypothyroidism in particular, can also slow your metabolism and promote weight gain. According to a 2016 review published in Mediators of Inflammation, inflammation and oxidative stress may increase the risk of thyroid issues (21). Hypothyroidism can, however, cause weight gain and obesity and drive further inflammation, leading to a vicious cycle of inflammation, obesity, and thyroid issues (22).

Chronic inflammation and obesity are underlying risk factors among many chronic and modern-day health issues. A 2020 study published in Circulation Research has found a link between metabolic inflammation, obesity, insulin resistance, and diabetes (23). According to a 2021 review published in Frontiers in Cardiovascular Medicine, inflammation plays a role in obesity and cardiovascular disease (24). 

According to a 2013 review published in the Journal of Obesity, obesity may increase the risk of cancer (25). According to a 2018 review published in the Journal of Allergy and Clinical Immunology, obesity may increase the risk of asthma (26). According to a 2014 study published in the International Journal of Epidemiology, obesity may increase the risk of autoimmune disorders (27).

The list goes on. Research clearly indicates a connection between obesity and the increased risk of chronic inflammation and inflammatory diseases. Reducing the risk of obesity, weight loss for obese individuals, and maintaining a healthy weight are essential for reducing chronic inflammation and the risk of chronic health issues.

Tips for Weight Loss

If you want to reduce your risk for chronic inflammation and chronic health issues, follow my tips for weight loss and maintaining a healthy weight:

  • Follow a nutrient-dense diet. Eat plenty of greens, vegetables, fruits, herbs, and spices. Choose healthy fats, such as avocados, olives, extra-virgin olive oil, coconut oil, grass-fed butter and ghee, nuts, seeds, nut butter, and fatty fish. Choose healthy sources of protein, such as grass-fed meat, pasture-raised poultry and eggs, wild-caught fish, beans, gluten-free whole grains, quinoa, amaranth, nuts, and seeds. Alter this list if you have histamine intolerance issues, since avocado or fish may not be for you, for example.
  • Follow a low-histamine diet. This is an important step if you have mast cell activation issues or histamine intolerance. Reduce or avoid high-histamine foods and choose low-histamine, nutrient-dense options.
  • Hydrate your body. Start your day with 16 to 32 oz of purified water. Drink a glass of water every one or two hours throughout the day. Add some green juices, green smoothies, or herbal tea, and eat hydrating veggies and fruits, such as cucumber, celery, peach, or pomegranate, for additional hydration.
  • Avoid liquid calories. Avoid empty liquid calories, such as soda, energy drinks, fruit juice, sugary drinks, creamy lattes, and other high-calorie drinks. They only add extra calories and increase inflammation without any nutritional benefits. 
  • Support your gut microbiome. Eat plenty of prebiotic-rich foods that feed the good bacteria (probiotics) in your gut, such as Jerusalem artichokes, asparagus, leeks, onion, garlic, apples, and bananas. Eat plenty of probiotic-rich fermented foods, including sauerkraut, kimchi, fermented vegetables, fermented herbs, coconut kefir, coconut yogurt, and kombucha (unless histamine intolerance is an issue for you). Take a high-quality probiotic supplement daily.
  • Try intermittent fasting. Intermittent fasting is among my favorite weight loss tips that involve a period of short-term fasting each day, leaving a shorter window for your meals than you are used to. Intermittent fasting eliminates after-dinner snacking and removes a lot of unnecessary calories. It may reduce your daily calorie intake without calorie counting.
  • Eat mindfully. Mindful eating is so important for weight loss and weight maintenance. Pay attention to your body while eating. Chew your food well. Eat slower to get in touch with your hunger clues. Avoid mindless eating at your desk, in your car, while watching TV, while scrolling social media, or when stressed.
  • Move your body regularly throughout the day. Get up and stretch regularly. Take a stroll in the morning and/or during lunch. Exercise at least 5 days a week for 20-30 minutes. Mix up cardiovascular and strength training workouts for maximum benefits, especially if exercise-related mast cell activation is not a problem for you.
  • Reduce stress. Try practicing meditation, breathwork, relaxation techniques, gratitude, yoga, tai chi, qi gong, and journaling. Spend time outdoors walking, hiking, gardening, or just sitting and connecting with nature. This is vital, to avoid cortisol excess and mast cell activation.
  • Eat a chemical-free diet. Choose organic produce whenever possible. If it’s not possible to buy only organic, always wash and peel non-organic produce. Buy organic, grass-fed, and pasture-raised meat, poultry, and eggs to avoid exposure to hormones. Reduce the use of plastic packaging, especially BPA. Choose glass or aluminum water bottles, glass containers, silicone ziplock bags, and ceramic or bamboo dishware.
  • Identify food sensitivities. Foods you are sensitive to, based on IgG antibody reaction and not simply histamine intolerance, can cause inflammation even if they are nutrient-dense and healthy for others. Common food sensitivities include gluten, wheat, dairy, fructose, peanuts, soy, and shellfish. However, you may find that your body has other, less common food sensitivities. I recommend following an elimination diet to identify your food sensitivities, then removing your triggering foods from your diet.  Or ask your health provider about specific testing for this purpose beforehand.

Next Steps

Are you interested in losing weight and improving your mast cell-related symptoms? 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.

Learn more about working with Dr. Gannage