In my clinical practice, I often encounter clients who come in with persistent, unexplained symptoms—fatigue, joint pain, and skin rashes—yet they’re left without clear answers for months, even years. They may have positive ANA (antinuclear antibodies), a common marker for autoimmune diseases, but the road to an official lupus diagnosis is long and winding. 

Lupus, with its ability to affect multiple systems in the body, can be one of the most difficult autoimmune diseases to diagnose. It can leave clients feeling frustrated and without proper treatment. Over time, I’ve found that looking deeper into the root causes has often provided relief, even before a formal diagnosis is made.

Here are five lesser-known contributors to lupus that I’ve seen play a significant role, along with natural therapies to help address them.

1. High oestrogen metabolites and DNA damage

One aspect of lupus that’s often overlooked is the role of high oestrogen metabolites, specifically the 4-hydroxyestrone (4-OHE1) metabolite. This metabolite can generate reactive oxygen species (ROS), leading to oxidative stress and DNA damage. In lupus patients, estrogenic activity is heightened, particularly in women, who make up the vast majority of lupus cases. The 4-OHE1 metabolite can directly bind to DNA, forming DNA adducts, which the immune system recognises as abnormal. This, in turn, provokes an autoimmune response, triggering lupus flares.

Several clients I’ve worked with were unaware that their hormonal imbalances could be contributing to their autoimmune symptoms. After testing oestrogen metabolites as part of the hormone panel that I offer in my clinic, we found that elevated 4-OHE1 was driving oxidative stress, and they often had worse symptoms around their menstrual cycles.

I recommend including broccoli sprouts, which are rich in sulforaphane, in their diet. Sulforaphane enhances phase II detoxification pathways in the liver, helping to clear these harmful oestrogen metabolites. Additionally, cruciferous vegetables like kale, cabbage, and cauliflower support this process and may reduce the oestrogenic burden on the immune system.

You can assess oestrogen metabolites through the DUTCH Plus test, which is explained in more detail here. This can help determine whether oestrogen metabolism is a factor in your health and potentially contributing to your lupus symptoms.

2. Chemical toxicity

Chemical toxicity, particularly from environmental pollutants like heavy metals (e.g., mercury, lead), industrial chemicals, and pesticides, can play a significant role in lupus. These toxins accumulate over time, disrupting normal immune function and causing oxidative stress. They are known to interfere with cellular function, damaging the mitochondria, impairing detoxification pathways, and provoking chronic inflammation—all of which contribute to the development of lupus.

I recall a client who had been exposed to high levels of chemical solvents in their workplace and experienced a gradual onset of lupus symptoms. Through functional testing, we found elevated levels of mercury and cadmium, which were contributing to her inflammatory symptoms and immune dysregulation.

Detoxification isvitaly for clients with high chemical burdens. In these cases, I emphasise the importance of a nutrient-dense detoxification protocol, which includes glutathione support via N-acetylcysteine (NAC) and alpha-lipoic acid. I also recommend sweating therapies, like infrared saunas, to help mobilise and eliminate stored toxins – although not all toxins can be detoxified in this way. Increasing intake of detoxifying foods like cilantro, chlorella, and garlic can support this process.

You can also read my article on how mould toxicity may contribute to the development of autoimmune disease here.

3. Folate deficiency and methylation imbalance

Folate, or more precisely, its active form (5-MTHF), is critical for DNA repair and methylation—a biochemical process that regulates immune function and inflammation. Folate deficiency, often due to genetic variations such as the MTHFR mutation, can lead to elevated homocysteine levels. High homocysteine has been linked to increased oxidative stress, impaired detoxification, and chronic inflammation, all of which are associated with lupus flares.

Several clients with lupus I’ve worked with had undiagnosed MTHFR genetic variations, which impaired their ability to convert folic acid into its active form. This deficiency exacerbated their inflammatory symptoms, and once we addressed it with the suitable form of folate, their flare-ups became less frequent.

For clients with methylation issues, I recommend methylated folate (5-MTHF) supplementation to lower homocysteine and improve methylation. Folate-rich foods like dark leafy greens, legumes, and asparagus should also be staples in their diet. For those with MTHFR mutations, I recommend avoiding synthetic folic acid which are often in fortified foods, as it can exacerbate the problem.

You can also listen to this episode of The Autoimmune RESET Podcast for a deeper insight into the vital link between folate deficiency and lupus here.

4. Chronic viral infections

Chronic viral infections, particularly from viruses like Epstein-Barr Virus (EBV), are another hidden driver of lupus. EBV can remain dormant in the body for years but may reactivate during periods of stress or immune suppression. This reactivation can lead to immune system confusion, where the body begins attacking its own tissues in response to viral proteins. Research has shown a strong link between EBV reactivation and lupus onset, especially in those with genetic susceptibility.

In practice, I’ve observed clients with a history of severe viral infections who later developed lupus. Their flare-ups often correlated with times of stress, and we later confirmed EBV reactivation through testing.

For managing chronic viral infections, I recommend immune-supporting nutrients like vitamin C, zinc, and lysine, which help suppress viral replication. Herbs such as astragalus and olive leaf extract also have antiviral properties and can help strengthen the immune system against EBV reactivation.

In addition to nutritional support, regulating the nervous system plays a crucial role in managing viral reactivation and supporting immune resilience. One tool I highly recommend is Nurosym, a clinically validated vagus nerve stimulation device designed to support autonomic balance and reduce chronic inflammation. You can get 5% off a Nurosym device using my affiliate code VH5.

Finally, incorporating daily stress management practices—such as breathwork, mindfulness, and gentle movement—is essential for reducing the internal stress load that can otherwise impair immune recovery.

5. Gut dysbiosis and leaky gut syndrome

Gut health is intimately linked to immune regulation. In those with lupus, gut dysbiosis (an imbalance in the gut microbiome) and leaky gut syndrome (increased intestinal permeability) are common. A compromised gut lining allows toxins, undigested food particles, and harmful bacteria to enter the bloodstream, triggering systemic inflammation and immune dysfunction. This ‘leaky gut’ can exacerbate lupus symptoms and drive autoimmunity.

Many of my clients with lupus also presented with significant digestive issues, including bloating, food sensitivities, and IBS-like symptoms. We identified gut dysbiosis and leaky gut syndrome through stool testing, which revealed low levels of beneficial bacteria and increased markers of intestinal permeability like zonulin.

I focus on repairing the gut barrier through a protocol that includes for those who can tolerate it, saccharomyces boulardii (SB), a yeast-based probiotic that can reduce gut inflammation and promote gut healing. Omega-3 fatty acids, found in oily fish or supplements, are also crucial for reducing systemic inflammation and healing the gut lining. Glutamine supplementation and bone broth can help repair the intestinal barrier.

Another valuable addition to gut repair is Symprove, a water-based probiotic designed to effectively deliver live bacteria to the gut. Many people find it an excellent support for rebuilding a healthy microbiome. You can get 50% off your first order of Symprove using my affiliate code AN50.

The symptoms of lupus can manifest in various ways, but the following are commonly seen: sensitivity to sunlight, which can cause rashes or worsen other symptoms; chronic inflammation in the joints, often affecting the hands, wrists, and knees; and a butterfly-shaped rash across the nose and cheeks, a signature symptom of lupus. Persistent, debilitating fatigue is also common and can be one of the most challenging symptoms.

And then, in my serious causes, lupus can cause nephritis, which can lead to kidney inflammation and cognitive issues such as difficulty concentrating or memory loss.

Lupus is a complex condition with multiple root causes. Addressing these underlying factors—hormonal imbalances, chemical toxicity, nutrient deficiencies, viral infections, and gut health—can lead to significant improvements in symptoms and long-term disease management. 

In my clinical practice, I’ve seen how personalised protocols focusing on these root causes can offer hope to those struggling with lupus, often before a formal diagnosis is even made. Working with a nutritionist or healthcare provider who understands the complexities of autoimmune diseases is critical to finding relief.

For more detailed guidance, you can download The Autoimmunity Recovery Plan here, or book a free discovery call with me here to learn more about the services that we offer at the Autoimmune Nutrition Clinic.

VJ Hamilton, BSc, RNT

VJ Hamilton is a Registered Nutritionist (BANT) and an expert in autoimmune disease. VJ combines her knowledge from her medical science degree in Biochemistry & Immunology with Nutritional Therapy to offer a thorough and personalised approach to support her clients based on the most current scientific research. VJ runs a virtual and in-person nutritional therapy and functional medicine practice, The Autoimmunity Nutritionist, specialising in gut skin and immune health.