Disclaimer: The information collated below comes from my friend who is a biochemist and has been fighting TNBC for over 5 years. Furthermore, some of the below come from cancer groups where some of my friends exchange their views, information from the research papers and share their experiences. I am not a doctor and any of the below is not intended as any medical advice. I am merely sharing things I wish I had researched and started so much earlier when my dad was ill, I hope it helps whoever is interested!
How to avoid metastases when diagnosed with cancer?
If you happened to be diagnosed with localized cancer the most important thing is to avoid metastases. Avoid inflammation. Any form of inflammation and healing triggers angiogenesis (this is the hallmark of cancer and is responsible for cancer progression and mets).
These compounds listed below would be a good starting point for a person newly diagnosed with cancer*. They may help contain the tumor (s) while organising a second (and third) opinion, reading Jane’s McLelland book, and changing one’s lifestyle and diet**! I would suggest to anyone newly diagnosed to get involved with their own treatment when also focusing first on strengthening the immune system and taking supplements that prevent metastasis while they learn about cancer metabolism.
- vit D3K2MK7
- MCP – Modified Citrus Pectin(Pectasol)
I noticed that while individuals are happy to accept high doses of toxic chemotherapy, they are reluctant to take appropriate high doses of supplements, and commonly take ineffective doses. When opting for a less conventional approach or adding it on the top of the standard treatment the doses of the supplements taken must be high to be effective and the quality/brand is crucial. Equally important is choosing regular monitoring tests which don’t cause further problems, and adjusting supplementation and doses accordingly.
*These compounds aren’t cytotoxic and won’t induce apoptosis, the idea here is to prevent cancer from metastasizing, so there is less feeling of urgency to make decisions, as often the decisions we make regarding cancer treatments (the good and the bad ones) have long term consequences and it is important to have time to figure out what is right for each person.
**There are also some dietary changes (avoiding any oils with cause inflammation such as omega 6) & cooking with olive oil or coconut oil instead, using some coconut butter and very little butter. Avoiding sugar, gluten, dairy, etc… basically anything that causes inflammation. To drink lots of black coffee, green tea with tulsi, danshen with amla and bitter melon (bitter gourd).
How to strengthen the immune system ahead of cancer treatment
All the above-mentioned supplements not only may help to contain the cancel locally but may also help to strengthen the immune system. There are a few more to add to the list, so let’s go through all of them to understand why they are important.
High dose (and high-quality!) vit D3 K2MK7
Knowledge about vitamin D metabolism is limited and often based on old concepts. This is also true for some naturopaths and nutritionists. Most people with cancer have low levels of this vitamin, and people who also suffer from auto-immune conditions have faulty receptors for vitamin D and lack the main co-factors for the conversion. While small doses (5,000ui/daily and lower) might be of some use, they would rarely control deficiencies, particularly for people with high inflammatory markers such as high CRP. I have much more info re vit. D from my dear friend who used Coimbra protocol to successfully fight her auto-immune illness and later to aid her cancer treatment. It is saved here under vit D K2MK7.
Please remember that when taking a high dose of vit. D calcium absorption is increased but osteocalcin and matrix-GLA arent activated. The protein osteocalcin, synthesized by bone cells called osteoblasts, deposits calcium in bones when activated by vitamin K2. As part of this process, osteocalcin binds to hydroxyapatite in a K2-dependent carboxylation reaction. Hence high dose vitamin D supplementation (above 20,000ui/daily) should be taken alongside good quality supplemental K2 mk7 (and Mg). It is also important to limit dietary calcium to also not to force kidneys to filter more of it.
Matrix-GLA is another protein involved in a process of calcium being deposited in blood vessels and soft tissue. When Matrix-GLA is carboxylated by the enzyme gamma-glutamyl carboxylase in a K2 dependant reaction vascular mineralization is inhibited.
People with Primary Hyperparathyroidism (PHPT) or Sarcoidosis, and other Granulomatous Disorders should take extra caution with vitamin D. If you know or have any of these conditions, or if you experience hypersensitivity or negative effects due to vitamin D, please discuss it all with your health care provider to address these conditions, and plan with them how to safely resolve an existing vitamin D deficiency.
Melatonin– many researchers state melatonin dosage starting from 20mg is beneficial when aiding cancer treatments.
Dr. Pierpli, one of the world’s leading melatonin researchers, has
successfully used daily dosages ranging from 0.1 to 200 mg. That’s
a 2,000-fold difference between the lowest dose and the highest!
Studies on mice show that even at astronomical doses of 300 mg
per day for two years, there were no side effects.
- anticancer properties (it inhibits matrix metalloproteins MMP-4 and MMP-9)& protects against chemo radiation damage. Many cancer patients take it before their scans to offset the radiation-based scans side effects (e.g 300mg 2 hours before the scan as per comments from the cancer patients I am in touch with- who of course tested it).
- more about the anti-metastatic action of melatonin here.
- it can also help to block estrogen for Er+ cancers & does more at high doses: https://www.lifeextension.com/Magazine/2018/10/Melatonin-A-Promising-Protector-Against-Breast-Cancer
More about melatonin in this deck shared by the Riodian clinic.
There are many studies showing the ability of DHA found in Omega 3 to help kill the tumor and avoid mets. It is true for many cancers.
Research has demonstrated that ω-3PUFAs can induce apoptosis in breast cancer cells by inhibiting the PI3K/AKT signal transduction pathway, and that ω-3PUFAs can improve the effectiveness of chemotherapy drugs.
DHA and resveratrol help prevent bone metastasis, DHA inhibits osteoclastogenesis by suppressing TNF-α and NF-κB signalling (DHA enhances anti-inflammatory IL-10 secretion and reduced the expression of pro-inflammatory M1 (F4/80+/CD11+) macrophages while also inhibiting production of many important angiogenic mediators such as VEGF, PDGF, PDECGF, COX-2, PGE2, nitric oxide, matrix metalloproteinases and β-catenin source: https://pubmed.ncbi.nlm.nih.gov/19493674/)
DHA is effective from 2g onwards. I used to buy this brand: Now Foods DHA-500.
Modified Citrus Pectin – MSCP (Pectasol)
Modified Citrus Pectin from PectaSol (Pectasol sells quality patented products). MCP affects growth factors like VEGF and blocks angiogenesis. Ultimately MCP inhibits or reduces galectin 3Galectin-3 interacts with glycoproteins, glycolipids, and the extracellular matrix. It is easy to get in the US bit harder in the UK. I rely on eBay (yes it is a bit pricey but at least is not stuck at customers…)
Dose: The recommended dosage is 1 scoop or 6 caps three times daily at least 30 min away from food. Many of us take 1.5 scoops or 9 caps twice daily. It’s important to get a baseline Galectin-3 blood level if you can. That may be difficult in the UK & easier in the US. For cancer, your goal is to keep it at 10 or lower according to Dr Nasha Winters. MCP is not going to kill cancer cells but it does block cancer cells from forming tumors. I don’t think it will hurt during a kill phase (refer to Jane’s MacLelland book to see what is kill phase is), and keeping a consistent dose is important. The unflavored powder is the cheapest. It can be taken in strong tea-like Good Earth herbal to make it taste good. Some people like the flavored version or take the pills or new chewables. You want to let it sit in the tea (or warm water) for 5 minutes before stirring. It mixes better that way.
Feverfew (parthenolide) to inhibit FAK1 activity (focal adhesion kinase and NF-kappaB).
Iodine to decrease the expression of several invasion markers and matrix metalloproteinases. More information on iodine in this wonderful book from Lynne Farrow ‘The Iodine Crisis: What You Don’t know About Iodine Can Wreck Your Life’
Medicinal mushrooms are a little slow to work, they take a few months. I tested Chaga mushrooms from Mushroom Science – as it is a reputable brand. Worth considering is also reishi & PSK =turkey tail.
LDN has received plenty of attention recently because of its ability to reverse autoimmune conditions from Crohn’s to Multiple Sclerosis, as well as for its impact on reducing glial inflammation. While LDN appears to have some use in a variety of conditions, it seems to show particular promise in cancer protocols as a result of its ability to reduce proliferation, inflammation and angiogenesis, and to modulate the immune system.
Naltrexone was developed as an opiate antagonist during the 70s to help tackle heroin addiction, and several events preceded the development of Naltrexone. The search for more effective pain relief led to the synthesis of morphine in Germany during the 1800s. At the time it seemed to offer the effective pain relief that the medical community so desperately needed, but it was quickly found to be highly addictive, with a significant risk of overdose. Decades later, and in search of a less addictive drug, Bayer developed diamorphine (more widely known as heroin), an acetylated form of morphine. Widespread addiction to morphine and heroin led to the need for opioid antagonists and during the 1940s, the production of intravenous naloxone began, still used in hospitals nowadays to treat opioid toxicity. Over a decade later, a similar drug, naltrexone, was produced. Naltrexone’s longer half-life made the compound effective in oral doses.
Dr Bernard Bihari was one of the first physicians to notice that LDN modulated immune system response and went on to study LDN’s effects in the context of HIV and other infections, with impressive results, particularly during the 80s when the medical establishment had no treatments that were less harmful than the disease itself. Dr Bihari, a Harvard-educated neurologist with impressive credentials, designed a few clinical trials with LDN but worked mainly with small groups of private patients. Even in the 80s he was already using LDN to treat a few cases of cancer and he noted that it reduced cell proliferation. Decades later, much is known about the structure and metabolism of the molecule, but despite naltrexone’s potential as an adjuvant in the treatment of many health conditions, it is an inexpensive drug and would not generate sufficient profit to prompt the pharmaceutical industry to invest in large scale trials.
Dr Nicholas Plotinikoff, a colleague of the late Dr. Bernard Bihari, who holds some of the patents on the drug, conducted several trials. Professor Ian Zagon, conducted trials and studies on the benefits of LDN for different types of cancer, and his papers are worth reading as they shed light on LDN’s mechanisms of action. In the UK, Professor Angus Dalgleish is one of the foremost authorities on LDN research. He consults privately but doesn’t appear to take NHS referrals.
Physicians are permitted to prescribe LDN off-label, however most are only aware of guidelines for using naltrexone 50mg and are unaware of the difference between naloxone and naltrexone. Having little to no training on the effects of the drug in low doses and not being aware of the lack of toxicity, most are reluctant to prescribe LDN. Naltrexone is produced as 50 mg tablets, and smaller doses must be compounded by a pharmacist or suspended in distilled water.
LDN is not a cytotoxic compound, and while it decreases cell proliferation it won’t cause apoptosis. It does, however, contribute to increased immune surveillance of detached tumor cells, reducing the likelihood of these cells moving unnoticed and metastasizing. Tumors can use several mechanisms to avoid recognition by immune surveillance. If the immune system is unaware of these abnormal cells or has no access to the tumor microenvironment, LDN alone will not cause the immune system to ‘’attack’’ the tumor as such but may help to contain the primary tumor and prevent metastasis, as primaries themselves are rarely a concern if they are kept in check.
Clinical trials in 1974 to assess human safety and risks suggested that oral intake of naltrexone up to 300 mg daily was safe, with little to no side effects. Naltrexone has been marketed in the past as Trexan, Revia, Antaxone, Celupan, Narolex and Nemexin and a few other names depending on the preparation and the pharmaceutical company producing it.
The chemical structure of Naltrexone is C20H22NO4-HCL and has a half-life of 4 to 6 hours. Naltrexone is sold as a racemic mixture of levo- and dextro- enantiomers. These enantiomers seem to antagonise different cell receptors. Levo-naltrexone is proposed to be an opioid receptor antagonist, consequently increasing endorphin production and inhibiting cell proliferation. The dextro enantiomer is suggested to be an antagonist for some Toll-Like Receptors such as TLR4 and TLR9, reducing inflammatory cytokines and angiogenesis. In our bodies many cells such as brain, immune and tumour cells present these opioid receptors on their surface. While naltrexone is attached to these receptors, our bodies are ‘fooled’ into continuing to produce monoamines and neuropeptides such as dopamine, serotonin, acetylcholine, norepinephrine.
As with many compounds, depending on the dose and preparation, different concentrations of Naltrexone exhibit different pharmacokinetics and affect cell growth and metabolism in different ways. At higher concentrations, naltrexone stimulates cell growth, while at low concentrations it inhibits cells growth. At high doses, 50 mg daily causes a constant blockage of the receptors and increases cellular growth which promotes healing but could also facilitate tumor proliferation. At low doses of 0.5 to 4.5 mg, naltrexone covers these receptors transiently and once LDN is cleared from the body, there is a rebound effect. The increased level of endorphins and upregulated met-enkephalin levels reduce cellular growth, suppressing tumor proliferation. This has been demonstrated in several in vitro experiments, in vivo trials, and case studies. Dose concentration also affects mood in different ways. Naltrexone 50mg causes depressive side effects as it continuously blocks receptors for endogenous endorphins. LDN in low doses only blocks these receptors briefly (for three to four hours depending on individual metabolism and liver clearance) and has the opposite effect, increasing endorphin levels and improving mood.
Naltrexone is a highly absorbable compound when administered intravenously. Oral doses are less bioavailable, only half of the amount ingested is absorbed as naltrexone, as between 40 to 50% is metabolised in the liver to 6-β-naltrexol, a metabolite that has a longer half-life of about 13 hours. The metabolite 6-β-naltrexol also acts as a weaker opioid receptor antagonist, however it doesn’t have a high affinity for the μ receptor.
Several studies concur that LDN interferes with the metabolism of glutamate, reducing its accumulation in the body. Glutamate is problematic for most types of cancer as it seems to upregulate calcium concentration in the tumour microenvironment, altering the cadherin-cathenin-calcium interaction needed to regulate cell adhesion and prevent metastasis. Another concern with increased intracellular levels of calcium is that it promotes the release of arachidonic acid with a consequential increase in COX enzymes contributing to inflammation, a mechanism used by cancer to promote angiogenesis. LDN not only interferes with this process by reducing glutamate levels, but it also interferes with the cyclin-dependent inhibitory kinase pathway, inhibiting angiogenesis.
There are several different opioid receptors on the surface of cells and they are highly specific. It is suggested that while LDN is non-selective, it has a higher affinity for μ-opioid receptors, but there is evidence that it does affect other receptors as well, though less effectively. Each of these receptors affects a different area of the body. Opioid analgaesics such as codeine, morphine, tramadol, and fentanyl act on these receptors, each affecting a specific receptor (mu, delta, kappa, OGF) depending on the intended result. The concentration of these compounds determines how long they will agonise/antagonise these receptors causing a very different effect.
Most cancer cells have over-expressed glutamine transporters (SLC1A5) to facilitate glutamine uptake in the cells while downregulating glutamate transporters (xCT) to increase intracellular glutamate concentrations. LDN is proposed to suppress this downregulation. High levels of glutamate in breast cancer seem to be a risk factor for bone metastasis. Glutamine is also an organic nitrogen donor to cancer cells, and nitrogen is necessary to synthesise the nucleotides and amino acids required for proliferation. Many types of cancers depend on glutamine metabolism and over-express kidney-type glutaminase enzymes, increasing the rate of glutamine conversion to glutamate. This process is also involved in the synthesis of asparagine and fatty acids, needed by the cancer cell to proliferate (providing an alternative source of carbon, normally provided by glucose, to form acetyl-CoA). Glutamate is involved in the regulation of the mechanistic target of rapamycin complex (mTORC1) activity and in the synthesis of glutathione, used by cancer cells as one of the mechanisms to survive the damage caused by excess reactive oxygen species (ROS). LDN’s ability to interfere with the glutamate transporter and reduce glutamate accumulation, therefore, interferes with many mechanisms used by cancer cells to survive and proliferate.
Despite all we know about naltrexone, the exact mechanism by which it affects cancer remains a little unclear. Naltrexone’s ability to act as an antagonist at Toll-Like Receptors (TLRs) affects downstream cellular signaling, down-regulating the NF-κβ signaling pathway. This is another important mechanism of action of LDN because NF-κβ signaling regulates the anti-apoptotic genes TRAF1 and TRAF2 and when up-regulated, protects cancer cells from apoptosis. Most cancers over-express NF-κB, enabling proliferation and facilitating metastasis.
This might explain why cancer patients taking LDN during the day still benefit, despite not seeing a significant increase in endorphins. There is some evidence that LDN mediated inhibition of TLR-4 and the consequent reduction in inflammatory cytokines reverses neuropathic symptoms. LDN seems also to be an antagonist to TLR-9, which is over-expressed in many tumors. When activated, both TLRs are involved in a cascade of events that produces inflammatory interleukins, tumor necrosis factor (TNF)-α, interferon-β, and nitric oxide. Antagonizing these TLRs, LDN reduces the synthesis of these inflammatory signaling cytokines. Cancer cells use inflammation to initiate angiogenesis and proliferation.
Another interesting effect of LDN is that it seems to block opioid receptors on the microglia, again reducing the secretion of inflammatory cytokines. In-vitro studies show that LDN reduces the microglial secretion of IL-1β.
LDN is absorbed in the gastrointestinal tract and most of it is eliminated through glomerular filtration in kidneys, hence it’s not hepatotoxic and doesn’t seem to alter liver enzymes. In order to benefit from LDN’s short half-life, it should be absorbed rapidly, and slow-release preparations are better avoided. If using a compounding pharmacy, it is better to choose one familiar with LDN, and have it compounded with Avicel, avoiding slow-release fillers. Avoid liquid suspensions with sugar or any form of sweetener. Calcium carbonate, often used as filler because it is inexpensive, is also better avoided.
LDN will be most effective when taken in the evening, however, Professor Zagon and Professor Bihari seem to have a different approaches on the importance of the correct timing. Endorphins are largely produced between 2 and 4 am. When the opioid receptors are transiently covered, the levels of endorphins produced will be much higher. Once LDN is cleared from the body, these endorphins will attach and activate the receptors previously blocked by the LDN and initiate a cascade of interactions that inhibit substance P, weakly negatively modulate GABA and increase the secretion of dopamine. Endorphins are primarily synthesized and stored in the anterior pituitary gland from a precursor protein called proopiomelanocortin (POMC). A smaller amount is produced by cells of the immune system that possess mRNA transcripts for POMC such as T-lymphocytes, B-lymphocytes, monocytes and macrophages.
Where to get LND from?
There are doctors prescribing it. You can look for one in your area at: https://www.ldnresearchtrust.org/LDN_Prescribers
Suspending Naltrexone in distilled water at home
If suspending Naltrexone in distilled water at home, use either a 5 or 10 ml syringe (without a needle) and measure 100 ml of diluent. Add and dissolve one 50 mg tablet and keep the solution in the fridge. If taking 4.5mg for example, fill the syringe (without the needle) with 9ml and take the solution at bedtime. Solutions of 100 ml result in less measurement error than more concentrated 50ml solutions.
A common complaint when starting to take LDN is insomnia. It seems that the body takes a few weeks to adjust to changes in endorphin production. For people prone to insomnia, or taking other medications which already disturb one’s sleep, or deplete magnesium such as proton pump inhibitors, it seems better to start with only 0.5 mg LDN and increase the dose by 0.5mg only while there are no symptoms. Slightly different doses have been proposed for different conditions, and 3 to 4.5mg seems an adequate dose for a cancer protocol. A few people complain of vivid dreams at this dose and for these, 3 to 3.5 mg seems to work better. Professor Angus Dalgleish has seen positive results with his patients using smaller doses.
A concern often raised is that if LDN increases immune response, it could potentially exacerbate autoimmune disorders. Published research, trials and most of the evidence we have suggests that it also up-regulates several regulatory interleukins and that it does not in any way promote inflammation, a clear indication that LDN does not affect the immune system indiscriminately. Continuous blockage of the opioid receptors deprives the body of its natural endogenous opioids, while on the other hand, a short-term blockage increases their levels. The effect is not from the naltrexone compound itself, but the fact that the receptor is temporarily antagonized and endorphins, enkephalins, and dynorphins are secreted at higher levels than usual, and then once the LDN is cleared from the body, these opioid peptides can perform their regulatory functions optimally.
It is worth remembering that as an opioid antagonist, LDN will make opioid pain relief medicines less effective. For people taking morphine, tramadol, codeine and other pain relief medicine long-term it could cause withdrawal symptoms. LDN usage should be suspended a day or two before any surgery as it would make pain control less effective. It can also make immune suppressant drugs less effective. Naltrexone is not metabolized by the CYP 450 system and does not seem to affect the metabolism of other medications.
There is little research into the effects of both naltrexone and its metabolite 6β-naltrexol when used during pregnancy and lactation. Both are detectable in breast milk and until there are further studies confirming its safety, it is not advisable to use it during pregnancy or when breastfeeding even though LDN has been used extensively to treat autistic children and is considered safe for children with cancer.
There are of course more supplements to explore:
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