Naltrexone (hereinafter NTX), an opioid antagonist, (1) combined in the right proportion with Alpha Lipoic Acid (hereinafter ALA), an antioxydant, has led to evidence-based successful cancer remissions (see ultra). Dr Burt Berkson is one of the leading authorities in this field. He has diligently published in peer review journals some of his clinical experience. (2) In an interview I conducted a few years ago with him (Cf ACR Institute’s HOM videos), Dr Berkson talked about Dr Behari’s “off label” use of this prescription drug (3) and confirmed that low dose Naltrexone (hereinafter LDN) with lipoic acid had synergistic effects, thanks to which a few of his patients were able to be cancer-free, including from pancreatic cancer. Dr Berkson told me he was able to present his findings at the National Cancer Institute. But the sad news is that so far, no one in the government nor in the biotech industry has decided to invest the many millions of dollars it would take to confirm the validity of this inexpensive LDN-ALA protocol via human clinical trials. As a consequence, we can’t have what is called scientific mainstream “hard evidence”.
Meanwhile, for the ACR Institute, what is interesting in this protocol is that it appears safe, cost friendly and efficient. What we don’t know is how efficient, given the lack of prospective trials. But we do know that a few terminal-branded cancer patients were able to overcome their disease with this protocol, as well as other patients who had different types of auto-immune diseases. Moreover, from the “basic science” point of view, this protocol is also interesting because it addresses some of the roots of cancer, notably the metabolic and immunity pathways of carcinogenesis.
NALTREXONE GETS AT THE ROOT OF CANCER
Naltrexone (NTX) is an opioid antagonist that inhibits or accelerates cell proliferation in vivo when utilized in a low (LDN) or high (HDN) dose, respectively. As a pharmacologically active opioid antagonist, NTX works by blocking opioid receptors, which in turn helps activate the body’s immune system. in particular naltrexone appears to targets the opioid growth factor (OGF)/opioid growth factor receptor (OGFr) pathway to inhibit cell proliferation. It looks like it is through this mechanism that LDN is thought to exert its inhibitory effect on cancer growth.
In this perspective, research by professor Ian S. Zagon of The Pennsylvania State University found that OGF regulates the growth of cancer cells (ie, and all cancer cells use the OGF-OGFr pathway in growth regulation).
“…we now demonstrate at the molecular level that the OGF-OGFr axis is a common pathway that is essential for the regulation of cell proliferation by NTX” (…) Thus, the common denominator of intermittent opioid receptor blockade by short-term NTX or LDN on ovarian cancer proliferation and tumorigenesis recorded herein appears to be related to the OGF-OGFr axis. These preclinical data may offer a non-toxic and efficacious pathway-related treatment that can benefit patients with ovarian cancer. (4)
LDN also promotes the maturation of dendretic cells. By enhancing maturation of bone marrow dentretic cells (BMDCs), T cells get better activated, that which can induce the secretion of higher levels of IL-12 and TNF-a:
“Our study has provided meaningful mode of action on the role of LDN in immunoregulation, and rationale on future application of LDN for enhancing host immunity in cancer therapy and potent use in the design of DC-based vaccines for a number of diseases. (5)
Naltrexone also works on other healing pathways, including, but not limited to the anti-inflammation, genomic and neuro-circuity pathways, thanks to which the patient’s wellbeing is better ensured.
“Accumulating evidence suggests that LDN can promote health supporting immune-modulation which may reduce various oncogenic and inflammatory autoimmune processes. Since LDN can upregulate endogenous opioid activity, it may also have a role in promoting stress resilience, exercise, social bonding, and emotional well-being, as well as amelioration of psychiatric problems such a autism and depression. It is proposed that LDN can be used effectively as a buffer for a large variety of bodily and mental ailments through its ability to beneficially modulate both the immune system and the brain neurochemistries that regulate positive affect.” (6)
Furthermore, when combined with alpha lipoic acide (ALA), (7) LDN appears to work better. In a peer reviewed published study, Drs Berkson (father and son), explain that ALA can reduce oxidative stress, can stabilize NF(k)B and stimulate pro-oxidant apoptotic activity. (8) In addition, ALA has a discriminative ability to discourage the proliferation of malignant cells. (9) By combining it with LDN, the endogenous immune response is thus enhanced even more. (10)
ANECDOTAL AND TESTIMONIAL EVIDENCE
In support of LDN as a stand-alone intervention against cancer, different pieces of testimonial evidence published in peer review literature exist, one of which concerned metastatic hepatocellular carcinoma. (11)
When combined with ALA, the results appear to be even better, Drs Berkson explain:
“ The authors, in a previous article, described the long-term survival of a man with pancreatic cancer and metastases to the liver, treated with intravenous alpha-lipoic acid and oral low-dose naltrexone (ALA/N) without any adverse effects. He is alive and well 78 months after initial presentation. Three additional pancreatic cancer case studies are presented in this article. At the time of this writing, the first patient, GB, is alive and well 39 months after presenting with adenocarcinoma of the pancreas with metastases to the liver. The second patient, JK, who presented to the clinic with the same diagnosis was treated with the ALA/N protocol and after 5 months of therapy, PET scan demonstrated no evidence of disease. The third patient, RC, in addition to his pancreatic cancer with liver and retroperitoneal metastases, has a history of B-cell lymphoma and prostate adenocarcinoma. After 4 months of the ALA/N protocol his PET scan demonstrated no signs of cancer.” (12)
Naltrexone molecule: Courtesy of PD
LDN has been a FDA-approved drug for over two decades for the treatment of heroin and alcohol addiction. Its “off label” use in low dose has been found to be safe and efficient for multiple autoimmune diseases including cancer. It provides a safe and inexpensive method of medical treatment by mobilizing the natural defenses of one’s own immune system. (13) But NTX has not yet been submitted for FDA approval at low dose for these diseases. None of the pharmaceutical giants want to invest in Naltrexone, let alone in the LDN-ALA protocol, because this combo is inexpensive and can’t be patented. ALA is a natural molecule found in supplement store and naltrexone has been without patent protection for many years, no pharmaceutical company will therefore bear the expense of the large clinical trials necessary for FDA approval of LDN as a cancer treatment. As a medical-legal “hard evidence” consequence, no definitive conclusions can be drawn due to the lack of randomized control groups no one in the Cancer industry wants to invest in.
Nonetheless, pending prospective, controlled clinical trials on LDN, with or without ALA, in the treatment of cancer, and given the in vitro, the in vivo and different successful case reports, this LDN-ALA protocol can nonetheless be ipso facto used provided the patient is guided by a competent health care practitioner and puts in place a general integrative and holistic approach to healing. In its integrative oncology section, ACR Institute collects success stories with both LDN and ALA and via its workshops, teaches how this protocol has been used. (See the Institute’s Workshop and Reports on integrative oncology).
Top: Spinash is one food sources that has a decent amount of lipoic acid
PRECISION AND REFERENCE NOTES
(1) Naltrexone is an FDA approved drug that binds to and inhibits opiate receptors – whose primary known function is to bind endogenous opiates (endorphins and enkephalins) and reduce pain. These are the same receptors that morphine, heroine, and other opiate drugs bind to. The primary use of naltrexone is to rapidly reverse opiate toxicity, or in the chronic treatment of opiate addiction. Naltrexone was originally synthesised in 1963 and patented in 1967. Early trials of naltrexone in rats, rabbits, dogs and monkeys had determined that the drug was non- toxic at therapeutic levels, with very few side effects. The US FDA approved in 1984 in a 50mg dose as a treatment for heroin addiction (Dupont were asked to run trials and develop the drug by the US government National Institute on Drug Abuse), The same year, DuPont’s Naltrexone patent expired.
(2) Dr Burton M. Berkson MD MS PhD is President of the Integrative Medical Center of New Mexico and former Professor Rutgers University and Chicago State University and Adjunct Professor NMSU. Cf. Berkson BM1, Rubin DM, Berkson AJ., 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. Integr Cancer Ther. 2009 Dec;8(4):416-22.
(3) In 1985, Dr. Bernard Bihari discovered LDN enhanced patients’ response to infection with HIV, the virus that causes AIDS. Years later he found that his patients with cancer and autoimmune disease also benefited from LDN. According to Dr. Bihari, nearly a quarter of his patients had at least a 75 percent reduction in tumor size, and nearly 60 percent of his patients demonstrated disease stability. He believed LDN’s anti-cancer mechanism is likely due to an increase in the number and density of opiate receptors on the tumor cell membranes, making them more responsive to the growth-inhibiting effects of the already present levels of endorphins, which in turn induces apoptosis (cell death) in the cancer cells. As Dr Behari noted, endorphins are the hormones centrally involved in supporting and regulating the immune system. When he measured the levels of endorphins in the blood of AIDS patients, they were found to average only 25% of normal. Dr Bihari and this colleagues determined that low dose naltrexone might exert its effects on tumor growth through a mix of three possible mechanisms: By inducing increases of metenkephalin (an endorphin produced in large amounts in the adrenal medulla) and beta endorphin in the blood stream; By inducing an increase in the number and density of opiate receptors on the tumor cell membranes, thereby making them more responsive to the growth-inhibiting effects of the already-present levels of endorphins, which induce apoptosis (cell death) in the cancer cells; and by increasing the natural killer (NK) cell numbers and NK cell activity and lymphocyte activated CD8 numbers, which are strongly responsive to increased levels of endorphins. In this perspective, different studies have provided new insight into the mechanisms by which neuropeptides produced by the nervous system can alter immune responsiveness, in particular how natural cytotoxicity can be enhanced with beta-endorphin. Source Dr. Bihari examined around 450 patients with cancer, most of whom had failed to respond to standard treatments. From these, it has been claimed that an estimated 60 percent cancer patients had responded positively. See also by Elaine A. Moore “The Promise of Low Dose Naltrexone Therapy”, McFarland, 2009.
(4) Donahue RN, McLaughlin PJ, Zagon IS. Exp Biol Med (Maywood). Low-dose naltrexone targets the opioid growth factor-opioid growth factor receptor pathway to inhibit cell proliferation: mechanistic evidence from a tissue culture model; 2011 Sep;236(9):1036-50.
(5) Meng J, Meng Y, Plotnikoff NP, Youkilis G, Griffin N, Shan F. Low dose naltrexone (LDN) enhances maturation of bone marrow dendritic cells (BMDCs). Int Immunopharmacol. 2013 Dec;17(4):1084-9.
(6). Norman Brown, Jaak Panksepp, Low-dose naltrexone for disease prevention and quality of life Source
(7). LA is synthesized de novo from an 8-carbon fatty acid (octanoic acid) in mitochondria, where protein-bound LA functions as an enzyme cofactor Induction of glutathione synthesis: Glutathione is an important intracellular antioxidant that also plays a role in the detoxification and elimination of potential carcinogens and toxins. Studies in rodents have found that glutathione synthesis and tissue glutathione levels are significantly lower in aged animals compared to younger animals, leading to decreased ability of aged animals to respond to oxidative stress or toxin exposure (31). LA has been found to increase glutathione levels in cultured cells and in the tissues of aged animals fed LA (32, 33). Research suggests that LA may increase glutathione synthesis in aged rats by increasing the expression of γ-glutamylcysteine ligase (GCL), the rate-limiting enzyme in glutathione synthesis (34) and by increasing cellular uptake of cysteine, an amino acid required for glutathione synthesis (35).
(8). CF. Zachar Z, Marecek J, et al J Mol Med (Berl). 2011 Nov;89(11):1137-48.Wenzel U, Nickel A, and Daniel H, Apoptosis. 2005 Mar;10(2):359-68, Van de Mark K, Chen JS, Steliou K, Perrine SP, Faller DV. J Cell Physiol. 2003 Mar;194(3):325-40; Na MH, Seo EY, Kim WK Nutr Res Pract. 2009 Winter;3(4):265-71; Choi SY, Yu JH, Kim H. Ann N Y Acad Sci. 2009 Aug;1171:149-55.
(9). Kono Y, Inomata M, Hagiwara S, et al., Expert Opin Ther Targets. 2012 Mar;16 Suppl 1:S103-9; Shi DY, Liu HL, Stern JS, Yu PZ, Liu SL. FEBS Lett. 2008 May 28;582(12):1667-71.
(10). Berkson BM, Rubin DM, Berkson, 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. AJ. Integr Cancer Ther. 2009 Dec;8(4):416-22.
(13). Drs Berkson believe that the ALA-LDN protocol is most effective for autoimmune diseases like lupus and rheumatoid arthritis. But that it can nonetheless be used for cancer patients given the success these doctors have personally witnessed with this protocol.
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