LDN: Why Do Symptoms Sometimes Get Worse Before Getting Better?

by Dr. Sajad Zalzala (Updated on: ) 5 minute read

From the Desk of Dr. Z: AgelessRx Co-founder and Chief Medical Officer, Dr. Sajad Zalzala offers his insightful perspective on topics related to longevity. With a wealth of experience and a deep-seated passion for disease prevention and extending healthy lifespans, Dr. Z is dedicated to sharing his knowledge on the secrets to longevity. Today, he shares his knowledge on why symptoms may sometimes get worse after starting with LDN, and what you can do about it.

Here’s what we’ll cover in this blog post:

  • What is LDN & how it works
  • Why LDN may appear to worsen symptoms
  • How to manage symptom flares with LDN
  • When to expect improvement

Starting Low Dose Naltrexone (LDN) can be an exciting step in your wellness journey, especially if you’re managing symptoms related to autoimmune conditions, chronic pain, or inflammation. However, some patients may notice that their symptoms temporarily worsen before improvement. This experience, while unsettling, is often a normal part of the adjustment process when beginning LDN therapy.

What Is LDN & How Does It Work?

LDN works by modulating the immune system and increasing endorphin production, helping to reduce inflammation and improve immune balance over time. It’s commonly prescribed for patients dealing with symptoms of autoimmune diseases like multiple sclerosis, fibromyalgia, and Crohn’s disease, as well as chronic pain syndromes. But due to its immune-modulating effects, LDN may trigger initial symptom flares in some patients.

Why Might Symptoms Worsen at First?

It’s not uncommon for LDN users to experience a temporary increase in symptoms, such as heightened pain, fatigue, or flu-like symptoms. While this can be distressing, it’s usually a sign that the body is beginning to respond to the therapy. Here’s why this happens:

  • Shifting Immune Response: LDN helps the immune system recalibrate. During this process, some patients may initially experience increased inflammation as the body adjusts.
  • Detox and Adjustment Period: As LDN stimulates the body’s production of endorphins and influences inflammatory pathways, there can be an adjustment period that results in temporary discomfort.
  • Individual Sensitivity: Some individuals are more sensitive to the effects of LDN, and even low doses may cause stronger reactions before the body settles into the new treatment​.

These side effects usually last anywhere from 1 to 4 weeks as the body adjusts to the new treatment.

How to Manage Symptom Flares with LDN

Here are a few practical tips to help manage this initial phase when symptoms might temporarily worsen:

1. Start Low & Titrate Slowly

Begin with the lowest effective dose, typically around 0.5 mg to 1.5 mg, and gradually increase every few weeks. This “start low, go slow” approach helps reduce the risk of side effects and allows your body to adjust smoothly.

2. Consider Pausing & Restarting

If symptoms become too uncomfortable, temporarily stopping LDN for a few days and then restarting at a lower dose may help. Some patients benefit from switching to a liquid form of LDN for more precise dosing adjustments​.

3. Communicate with Your Doctor

Always stay in contact with your healthcare provider, especially if side effects persist or worsen. Your doctor can guide you in making adjustments to your dosage or timing of LDN to minimize discomfort.

4. Support Your Body’s Adjustment

During this period, it may help to incorporate anti-inflammatory supplements, eat a balanced diet, stay hydrated, and get adequate rest to support your body’s immune response.

5. Manage Your Symptoms

If you’re experiencing mild symptom flares like increased pain, fatigue, or inflammation, there are several over-the-counter (OTC) options to help you manage discomfort:

  • NSAIDs (Non-Steroidal Anti-Inflammatory Drugs): Medications like ibuprofen or naproxen can help reduce pain and inflammation. Be sure to consult your doctor before using these, especially if you have any underlying health conditions.
  • Acetaminophen (Tylenol): This can be a good option if NSAIDs are contraindicated or not tolerated, helping to ease pain without affecting inflammation.
  • Antihistamines: For those experiencing histamine-related reactions, such as skin rashes or itching, OTC antihistamines like cetirizine or diphenhydramine can help relieve symptoms. Again, always check with your healthcare provider to ensure it’s safe to use alongside LDN.
  • Topical Pain Relief: Creams and gels with ingredients like menthol, capsaicin, or lidocaine can provide localized pain relief without the systemic effects of oral medications.

These therapies can offer temporary relief while your body adjusts to LDN, helping you to stay more comfortable until the symptoms subside.

When to Expect Improvement

Many patients start to experience symptom relief within 4 to 8 weeks of starting LDN. However, the timeline can vary depending on individual sensitivity and the condition being treated. Patience is key, and working closely with your doctor can help ensure a smooth transition.

If you have concerns about starting LDN or need personalized advice, reach out to your AgelessRx provider for support. We’re here to help you make the most of your LDN therapy and manage any side effects you may experience along the way.

Note: The above statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

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