Low-Dose Naltrexone (LDN) for Cancer: An Evidence-Based Review of LDN in Integrative Oncology LDN Alpha Lipoic Acid Integrative Medicine

Edited by Yoon Hang Kim MD MPH

About Dr. Kim

Dr. Yoon Hang "John" Kim is a board-certified integrative medicine physician with over 20 years of clinical experience. He completed his integrative medicine fellowship at the University of Arizona under Dr. Andrew Weil and holds certifications in preventive medicine, medical acupuncture, and integrative/holistic medicine. Through his telemedicine practice, Dr. Kim specializes in utilizing LDN or Low Dose Naltrexone for treating autoimmune conditions, chronic pain, integrative oncology, and complex conditions including fibromyalgia, chronic fatigue, MCAS, and mold toxicity. He is the author of three books and more than 20 articles, and has helped establish integrative medicine programs at institutions nationwide.

Professional: www.yoonhangkim.com | Clinical: www.directintegrativecare.com

LDN Alpha Lipoic Acid Integrative Medicine

Cancer treatment has evolved well beyond chemotherapy and radiation. Integrative oncology—an approach that addresses both disease progression and quality of life—has become an increasingly important part of comprehensive cancer care. Among the most promising low-toxicity interventions is low-dose naltrexone (LDN). Originally developed as an opioid antagonist at higher doses, LDN shows remarkable immunomodulatory and anti-proliferative properties when given at doses between 1.5 and 4.5 milligrams. This review examines the current evidence for LDN in cancer treatment, how it works, and how it fits into broader oncology protocols.

Understanding Low-Dose Naltrexone in Cancer Therapy

At standard doses of 50 milligrams, naltrexone works as a continuous opioid receptor blocker—that's how it's used in addiction medicine. But something interesting happens at low doses. When we give just 3.0–4.5 mg at bedtime, LDN creates only a brief blockade of opioid receptors lasting a few hours. This temporary blockade triggers a rebound effect: the body responds by ramping up production of endogenous opioids, particularly endorphins and opioid growth factor (OGF, also known as met-enkephalin).

The opioid growth factor axis is central to how LDN works. OGF interacts with its receptor (OGFr) to inhibit DNA synthesis and cell division—a mechanism especially relevant in rapidly dividing cancer cells. By enhancing this natural regulatory system, LDN may suppress tumor growth while boosting immune surveillance. This dual mechanism sets it apart from conventional cytotoxic therapies. LDN may also be one of the first glial cell modulators used for chronic pain management.

I should be clear: LDN for cancer remains investigational. There are no official clinical guidelines or FDA approval for this use. That said, LDN has shown benefit in reducing symptoms in fibromyalgia, Crohn's disease, multiple sclerosis, and complex regional pain syndrome—giving us insight into its broader immunomodulatory effects.

The Berkson Protocol: LDN Combined with Alpha-Lipoic Acid

The most documented application of LDN in integrative oncology comes from the work of Dr. Burton M. Berkson, who developed the ALA/N protocol combining intravenous alpha-lipoic acid with oral LDN. This approach uses the complementary mechanisms of both compounds to target cancer through multiple pathways.

Alpha-lipoic acid (ALA) is a naturally occurring mitochondrial cofactor with remarkable versatility. In normal cells, ALA acts as a potent antioxidant—scavenging reactive oxygen species and regenerating other antioxidants like glutathione, vitamin C, and vitamin E. But here's what makes it particularly interesting for oncology: within the tumor microenvironment, ALA exhibits pro-oxidant properties that selectively disrupt cancer cell metabolism. It can protect healthy tissues while promoting oxidative stress in malignant cells.

The Berkson Protocol is most often used for solid tumors, where surgical and metabolic interventions are commonly considered together.

Mechanisms of Action: How LDN and ALA Target Cancer

LDN's therapeutic potential in cancer stems from several interconnected mechanisms. First, the transient opioid receptor blockade triggers upregulation of endorphins and OGF, which interact with OGFr to inhibit tumor cell proliferation. This antiproliferative effect has been demonstrated across multiple cancer cell lines, including pancreatic, hepatocellular, and renal malignancies.

Second, LDN enhances immune surveillance by modulating natural killer cell activity and T-lymphocyte function. Cancer cells frequently evade immune detection; LDN may help restore the immune system's ability to recognize and eliminate malignant cells. Third, LDN reduces inflammatory cytokines—specifically TNF-alpha and IL-6—and modulates the inflammatory tumor microenvironment that often promotes cancer progression.

Alpha-lipoic acid adds complementary anti-cancer mechanisms. ALA interferes with the Warburg effect—cancer cells' preferential reliance on glycolysis over oxidative phosphorylation—by promoting mitochondrial function and disrupting altered glucose metabolism. It also modulates NF-κB signaling, a key inflammatory pathway involved in cancer progression, metastasis, and treatment resistance. The combination of ALA's metabolic effects with LDN's immunomodulatory properties creates a comprehensive approach to cancer management.

Clinical Evidence: Case Reports and Outcomes

Let me be upfront: we don't have large randomized controlled trials for LDN in cancer. What we do have is a compelling body of case reports and small prospective series documenting remarkable outcomes, particularly in cancers with typically poor prognosis. LDN appears well-tolerated—the most common side effect is vivid dreams, seen in about 37% of patients.

Pancreatic Cancer

Dr. Berkson's initial publication described a patient with metastatic pancreatic adenocarcinoma—cancer that had already spread to the liver—who achieved long-term survival exceeding three years on the ALA/N protocol. The patient remained asymptomatic and professionally active. If you know anything about pancreatic cancer, you know this is extraordinary; median survival for metastatic disease typically measures in months, not years.

Subsequent reports documented three additional cases: one patient survived 39 months with liver metastases, another showed no evidence of disease on PET imaging after five months, and a third patient—who had concurrent pancreatic cancer, retroperitoneal metastases, B-cell lymphoma, AND prostate adenocarcinoma—demonstrated complete radiographic resolution of detectable malignancy.

Renal Cell Carcinoma, Prostate Cancer, and Other Malignancies

Extended survival and disease stabilization have been reported in stage IV renal cell carcinoma and hepatocellular carcinoma, with patients experiencing rapid improvements in energy and overall well-being after starting IV ALA. One notable case involved a patient with biopsy-confirmed follicular B-cell lymphoma who achieved complete radiographic resolution of metabolically active lymph nodes within six months using LDN alone—suggesting that LDN monotherapy may offer benefit in certain hematological malignancies.

A prospective case series by Schwartz and colleagues described disease stabilization across various advanced cancers, including dramatic PSA reduction in hormone-resistant prostate cancer. Toxicity was limited to transient nausea and occasional vomiting—a far cry from conventional chemotherapy's side effect profile.

Protocol Specifications and Clinical Implementation

The standard Berkson protocol consists of intravenous alpha-lipoic acid at 300–600 mg given two to three times weekly, combined with oral LDN at 3.0–4.5 mg at bedtime. Adjunctive components typically include oral alpha-lipoic acid (about 600 mg daily), selenium (200 mcg), and silymarin (900–1,200 mg daily) for liver protection. Some practitioners add intravenous vitamin C and hydroxycitrate.

Lifestyle modifications are essential—this isn't just about taking supplements. We emphasize anti-inflammatory nutrition, stress reduction, and appropriate physical activity. The protocol's safety profile is favorable; most adverse effects are limited to mild GI symptoms and occasional skin reactions. But proper patient selection and monitoring remain critical. This should be implemented under the guidance of physicians experienced in integrative oncology.

One important note: patients must inform their healthcare provider about other medications they're taking. LDN's interaction with opioid analgesics is a serious consideration—LDN is contraindicated in patients currently taking opioids, as even low doses can precipitate withdrawal.

LDN Beyond Cancer: Chronic Pain and Inflammation

While this article focuses on cancer, it's worth noting that LDN has shown consistent benefit for chronic pain conditions including fibromyalgia, Crohn's disease, and complex regional pain syndrome. The mechanism appears to involve modulation of microglial cells and enhancement of endogenous opioid production, reducing inflammatory responses and pain perception. In my practice, I've found LDN's exceptional safety profile makes it a valuable option for patients seeking relief from persistent pain.

LDN has also been shown to reduce not only self-reported pain in Crohn's disease but also objective markers of inflammation and disease severity. The anti-inflammatory effect extends beyond the central nervous system—we see suppressed inflammatory agents in peripheral macrophages as well.

Integrating LDN into Comprehensive Cancer Care

LDN offers several practical advantages as an integrative oncology intervention. It's well-tolerated, inexpensive, and has minimal drug interactions (with the important exception of opioids). It can often be used alongside conventional treatments, potentially improving quality of life and supporting immune function during chemotherapy or radiation. For patients who have exhausted standard therapies or prefer low-toxicity approaches, LDN represents a reasonable option for disease stabilization and symptom management.

But I want to be clear about the limitations. The evidence base consists primarily of case reports and small series—not large randomized trials. LDN remains investigational and isn't FDA-approved for cancer. And while it may stabilize disease and improve quality of life, it shouldn't replace evidence-based conventional treatments when those are appropriate. It's an adjunct, not a replacement.

Conclusion: The Future of LDN in Integrative Oncology

The evidence supporting LDN in cancer treatment, while still emerging, makes a compelling case for its inclusion in the integrative oncology toolkit. The ALA/LDN protocol pioneered by Dr. Berkson has documented remarkable outcomes in patients with advanced malignancies typically associated with poor prognosis. The mechanistic rationale—combining immunomodulation, antiproliferative effects, and metabolic targeting—provides a coherent scientific framework for these clinical observations.

Cancer isn't a single disease—it's many different conditions, and LDN's role may vary depending on cancer type and stage. Early detection and accurate diagnosis remain critical for optimizing outcomes. But for patients seeking comprehensive, low-toxicity approaches to cancer management, LDN represents a promising option that deserves serious consideration within the context of individualized, evidence-informed care.

As integrative oncology continues to evolve, LDN exemplifies the potential for repurposing established medications to address unmet needs in cancer care. The protocol's favorable safety profile, low cost, and preliminary evidence of efficacy warrant continued investigation through rigorous clinical trials. I look forward to seeing where the research takes us.

LDN Alpha Lipoic Acid Integrative Medicine

Disclaimer: This article is for educational purposes only and does not constitute medical advice. The ALA/LDN protocol remains investigational and should only be pursued under the guidance of qualified healthcare providers. Patients should discuss all treatment options with their oncology team.

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About the Author

At www.directinegrativecare.com Dr. Kim is dedicated to guiding you on your path to wellness through a deeply personalized and supportive approach. We focus on integrative medicine, looking beyond symptoms to uncover the root causes of chronic conditions and develop a treatment plan tailored specifically to your unique health journey. By combining compassionate care with innovative therapies, our goal is to empower you with the knowledge and tools needed to achieve lasting health. We invite you to explore our website to learn more about how our patient-centered practice can help you find balance and vitality. 

Clinical Practice: www.directintegrativecare.com

Professional: www.yoonhangkim.com

References

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Berkson BM, Rubin DM, Berkson AJ. Reversal of signs and symptoms of a B-cell lymphoma in a patient using only low-dose naltrexone. Integrative Cancer Therapies. 2007;6(3):293-296.

Berkson BM, Rubin DM, Berkson AJ. Revisiting the ALA/N (α-lipoic acid/low-dose naltrexone) protocol for people with metastatic and nonmetastatic pancreatic cancer: A report of 3 new cases. Integrative Cancer Therapies. 2009;8(4):416-422.

Berkson BM, Calvo Riera F. The long-term survival of a patient with stage IV renal cell carcinoma following an integrative treatment approach including the intravenous α-lipoic acid/low-dose naltrexone protocol. Integrative Cancer Therapies. 2018;17(3):986-993.

Schwartz L, Buhler L, Icard P, Lincet H, Steyaert JM. Metabolic treatment of cancer: Intermediate results of a prospective case series. Anticancer Research. 2014;34(2):973-980.

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