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Intravenous Alpha-Lipoic Acid (ALA) and Low-Dose Naltrexone (LDN) in Integrative Oncology and Hepatology: The Berkson Protocol San Antonio TX Quincy IL


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Historical Context  


Dr. Burton M. Berkson pioneered the use of intravenous alpha-lipoic acid (ALA) combined with oral low-dose naltrexone (LDN) as an integrative protocol for patients with advanced cancer and liver disease. His initial case reports, dating back to the early 2000s, described unexpectedly long-term survival and clinical improvement in patients with metastatic pancreatic cancer and renal cell carcinoma who had exhausted conventional therapies.[1][2][3] The protocol’s safety and apparent efficacy prompted calls for further clinical investigation.


Pharmacological Mechanisms  


ALA is a mitochondrial cofactor with potent antioxidant and anti-inflammatory properties. It acts by scavenging reactive oxygen species, regenerating endogenous antioxidants (notably glutathione), chelating metal ions, and modulating inflammatory pathways.[4][5][6][7] In cancer, ALA exhibits unique pro-oxidative effects within the tumor microenvironment, disrupting redox balance and inhibiting cell proliferation through mechanisms such as Grb2-mediated signaling and interference with glycolytic metabolism (Warburg effect).[8][9][10] LDN transiently blocks opioid receptors, upregulating endogenous opioids and the opioid growth factor axis, which can inhibit tumor growth and modulate immune responses.[1][2][3]


Protocol Specifications  


The Berkson protocol typically consists of:


- Intravenous ALA: 300–600 mg, 2–3 times per week.


- Oral LDN: 4.5 mg nightly.


Adjuncts may include intravenous vitamin C and hydroxycitrate, alongside lifestyle modifications.[2][11]


Clinical Evidence  


Case reports and small series document long-term survival and disease stabilization in patients with metastatic pancreatic cancer, renal cell carcinoma, and other chemoresistant malignancies treated with the ALA/LDN protocol.[1][2][3][11] For example, Berkson et al. reported patients with metastatic pancreatic cancer and RCC achieving multi-year survival and radiographic remission, with minimal toxicity.[1][2][3] Schwartz et al. described a prospective case series in advanced cancer, noting disease stabilization and dramatic PSA reduction in hormone-resistant prostate cancer, with toxicity limited to transient nausea and vomiting.[11] Preclinical studies and reviews support ALA’s anti-proliferative effects in cancer models and its role in metabolic and oxidative stress modulation.[4][8][5][6][9][10]


In hepatology, ALA has shown promise in metabolic dysfunction-associated steatotic liver disease (MASLD), reducing hepatic fat accumulation and oxidative damage.[12] Its favorable safety profile and antioxidant effects make it a candidate for adjunctive therapy in liver toxicity and chronic liver disease.[4][5][12]


Implications for Contemporary Practice  


The Berkson protocol offers a low-toxicity, integrative approach for patients with advanced cancer or liver disease, especially those who have failed standard therapies. While case reports and small series suggest benefit, robust randomized controlled trials are lacking, and the protocol remains investigational. ALA’s mechanisms—antioxidant, pro-oxidant in cancer, metabolic modulation—are well characterized, and LDN’s immunomodulatory effects are increasingly recognized. The protocol’s safety profile is favorable, with most adverse effects limited to mild gastrointestinal symptoms and skin reactions.[4][5][11]


Conclusion  


The intravenous ALA/LDN protocol represents a promising, low-toxicity adjunct in integrative oncology and hepatology. Its historical use, mechanistic rationale, and encouraging clinical reports warrant further controlled studies to define its efficacy and optimal patient selection. Until then, it should be considered experimental, with careful monitoring and informed consent.


References:  


- Historical case reports and protocol details: [1][2][3][11]


- Mechanisms and pharmacology: [4][8][5][6][7][9][10]


- Hepatotoxicity and liver disease:[12]


At Direct Integrative Care, 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. 

Yoon Hang Kim MD

Integrative & Functional Medicine Physician

Virtual Practice Serving IA, IL, MO, FL, GA, and TX




References

  1. Revisiting the ALA/N (Alpha-Lipoic Acid/Low-Dose Naltrexone) Protocol for People With Metastatic and Nonmetastatic Pancreatic Cancer: A Report of 3 New Cases. Berkson BM, Rubin DM, Berkson AJ. Integrative Cancer Therapies. 2009;8(4):416-22. doi:10.1177/1534735409352082.

  2. 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. Berkson BM, Calvo Riera F. Integrative Cancer Therapies. 2018;17(3):986-993. doi:10.1177/1534735417747984.

  3. The Long-Term Survival of a Patient With Pancreatic Cancer With Metastases to the Liver After Treatment With the Intravenous Alpha-Lipoic Acid/Low-Dose Naltrexone Protocol. Berkson BM, Rubin DM, Berkson AJ. Integrative Cancer Therapies. 2006;5(1):83-9. doi:10.1177/1534735405285901.

  4. Therapeutic Applications of Alpha-Lipoic Acid: A Review of Clinical and Preclinical Evidence (1998-2024). Carnib BL, Souza EV, Floresta LRS, et al. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 2025;191:118480. doi:10.1016/j.biopha.2025.118480.

  5. Alpha-Lipoic Acid: Biological Mechanisms and Health Benefits. Superti F, Russo R. Antioxidants (Basel, Switzerland). 2024;13(10):1228. doi:10.3390/antiox13101228.

  6. Advances in Α-Lipoic Acid for Disease Prevention: Mechanisms and Therapeutic Insights. Wang Y, Jiang S, He Y, Pang P, Shan H. Molecules (Basel, Switzerland). 2025;30(9):1972. doi:10.3390/molecules30091972.

  7. Potential for Novel Therapeutic Uses of Alpha Lipoic Acid. Fasipe B, Faria A, Laher I. Current Medicinal Chemistry. 2023;30(35):3942-3954. doi:10.2174/0929867329666221006115329.

  8. The Multifaceted Role of Alpha-Lipoic Acid in Cancer Prevention, Occurrence, and Treatment. Yan S, Lu J, Chen B, et al. Antioxidants (Basel, Switzerland). 2024;13(8):897. doi:10.3390/antiox13080897.

  9. Lipoic Acid Inhibits Cell Proliferation of Tumor Cells in Vitro and in Vivo. Feuerecker B, Pirsig S, Seidl C, et al. Cancer Biology & Therapy. 2012;13(14):1425-35. doi:10.4161/cbt.22003.

  10. Integrated Transcriptomic and Proteomic Analyses Reveal Ɑ-Lipoic Acid-Regulated Cell Proliferation via Grb2-Mediated Signalling in Hepatic Cancer Cells. Yang L, Wang X, Xu J, et al. Journal of Cellular and Molecular Medicine. 2018;22(6):2981-2992. doi:10.1111/jcmm.13447.

  11. Metabolic Treatment of Cancer: Intermediate Results of a Prospective Case Series. Schwartz L, Buhler L, Icard P, Lincet H, Steyaert JM. Anticancer Research. 2014;34(2):973-80.

  12. Lipoic Acid in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Review. Liu F, Lv J, Chen Y, et al. Nutrition & Metabolism. 2025;22(1):56. doi:10.1186/s12986-025-00954-9.

 
 
 

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