Five Common Supplements That Have Shown Benefit In Glioblastoma Studies

[chartist]

Hello, my name is Art.

I joined this forum recently to share information about five supplements that have shown benefit for glioblastoma in studies. I hope this information will be useful in helping to deal with glioblastoma.

I only discussed two of the supplements in this original post and the other three supplements I discussed in the replies section. So you will have to scroll down to the replies to read about the other three supplements. The five supplements are :

1. Vitamin D

2. Melatonin

3. Berberine

4. Astaxanthin

5. Andrographis

The first supplement I would like to discuss is Melatonin. Melatonin has the ability to cross the blood brain barrier (BBB) which is useful in this case.

ncbi.nlm.nih.gov/pmc/articl....

A relevant quote from the above link confirming that melatonin crosses the BBB :

' One important characteristic of melatonin is its permeability into the brain. It readily passes through the blood-brain-barrier and accumulates in the central nervous system at substantially higher levels than exist in the blood. '

Melatonin also has anticancer effects as discussed in this next link :

cmbl.biomedcentral.com/arti....

Here is a very relevant quote from the above link describing some of the anticancer effects of melatonin :

' Moreover, the evidence is compelling that melatonin has a variety of anti-cancer effects, such as its inhibition of cancer cell viability, proliferation, progression, and metastasis or even inhibition of cancer initiation [3, 4]. '

Melatonin is also useful for use in people with GBM and also has synergy with temozolomide ( an antineoplastic used for GBM) as discussed here :

' Glioblastoma is the most prevalent primary tumor of brain. Furthermore, glioblastoma is a highly aggressive and lethal type of cancer; the average of life expectancy is reported to be less than 1 year after it is diagnosed. Because of the difficulty with complete surgical resection and high resistance of glioblastoma to existing chemotherapy agents, treatment of these patients remains exceedingly complicated. Therefore, there is an urgent need for developing unconventional therapeutic strategies in the treatment of patients with malignant glioblastoma. In the past few years, different investigations have shown the existence of stem cell-like cells in solid tumors involving malignant glioblastomas [75]. Stem cell-like cells are important built-in multidrug-resistant and pluripotent cells that commonly develop drug resistance and continue to proliferative after a chemotherapy regimen. Accordingly, the therapeutic approaches that cannot eradicate the brain tumor stem cells (BTSCs) are expected to be unsuccessful. While these treatments may be successful for killing an appreciable number of tumor cells and causing a transitory regression, they fail to alter cancer relapse [76]. For the purpose of achieving a persistent long-lasting treatment of glioblastoma patients, it is a requirement to discover and develop novel therapeutic strategies for targeting both BTSCs and tumor bulk.

Martin and colleagues [77] investigated the properties of melatonin and its combination with chemotherapeutic agents on these multi-drug resistant brain tumor stem cells. Results showed that melatonin and chemotherapeutic drugs in combination induced a remarkable synergistic toxicity against BTSCs and malignant A172 glioma cells. Co-treatment with temozolomide as current agent for remission of malignant glioma with melatonin, significantly correlated with down-regulated expression of ABCG2/BCRP and subsequent inhibition of ABC transporter functions. In fact, melatonin significantly elevated DNA methylation of the promoter of ABCG2/BCRP; thus, the expression properties and function of ABCG2/BCRP were prohibited due to the preincubation melatonin with a DNA methyltransferase inhibitor (DNMTi). Hence, their findings highlight a potent association between the decrease of ABCG2/BCRP activities and the synergistic toxicity of melatonin and therapeutic agents. By inducing DNA methylation in proto-oncogenes, melatonin also could be considered as a promising chemical for defeating multi-drug resistance in malignant glioblastomas, and improving the effectiveness of current chemotherapeutic regimens. '

Melatonin also synergizes with other drugs used to fight GBM as discussed here :

nature.com/articles/bjc2013....

Here is a relevant quote :

' Data presented here showed that combination of melatonin with chemotherapeutics has a synergistic toxic effect both in BTSC and glioblastoma cell lines. Thus, melatonin increases toxicity of several drugs including temozolomide, current treatment for malignant glioblastoma. '

The fact that melatonin can increase the toxicity toward GBM may allow for lower dosing of these chemotherapeutics in some cases where that would be desirable.

Melatonin can also help reduce the damage caused to the body by these chemotherapeutic and radiotherapy agents, which would be very useful in reducing unwanted chemo side effects as well as fight multidrug resistance, inhibit stem like cell proliferation in GBM and decrease the viability and inhibit the proliferation of glioblastoma cells as discussed here in this 2021 review:

ncbi.nlm.nih.gov/pmc/articl...

Here is a relevant quote from the review :

' Glioma stem-like cells are subpopulation in glioblastoma, they play a crucial role in the tumor growth maintenance and recurrence [152,153,154], and promote self-renewing capacity and tumor propagation [155,156,157]. Melatonin showed an anticancer effect against glioblastoma, and it was also reported to overcome the multi-drug resistance in glioblastoma treatment [158,159,160]. Sung et al. recently have investigated the impact of combination of melatonin with vorinostat on the expression of transcription factor EB and apoptosis in glioblastoma cells and glioma cancer stem cells. The expression of transcription factor EB, which needs oligomerization to regulate transcription, was reported to be increased in glioblastoma. The combination of vorinostat and melatonin induce a downregulation of the transcription factor EB and oligomerization, which increased apoptosis related gens, hence, cells apoptosis was activated [161]. In another study, Chen et al. have studied the roles of melatonin and the associated mechanisms against glioblastoma stem-like cells. Their results demonstrated that melatonin altered the glioblastoma stem-like cells biology and inhibited glioblastoma stem-like cells proliferation. Moreover, melatonin showed to alter the transcription factors profile inhibiting the initiation and propagation of tumor. In addition to the impairment of EZH2–STAT3 interaction and EZH2 S21 phosphorylation, melatonin has multiple roles in attenuating several key signals related to survival and self-renewal in glioblastoma stem-like cells [158]. Lai et al. have studied the microenvironment of glioma investigating the correlation of melatonin treatment and molecular markers in glioblastoma multiform including SIRT1, CCL2, ICAM-1, and VCAM-1. Their results showed melatonin administration increased the expression of SIRT1, which inhibit the growth and proliferation of glioma cells [162]. In another recent study, Fernandez-Gil et al. have explored whether treatment with melatonin can restore the oxidative phosphorylation after metabolic switch to glycolysis in glioblastoma cells. The results showed that melatonin significantly decreased the viability and inhibited the proliferation of glioblastoma cells. Besides, it modulates a metabolic shift from glycolysis to oxidative phosphorylation, which lead to a reduction in the malignant properties of glioblastoma cells [163]. Additionally, it was reported that the melatonin antitumor effect can be through suppression of the EZH2-NOTCH1 signaling axis in glioblastoma stem-like cells [164]. Moreover, several studies have shown the melatonin impact on glioblastoma cells via enhancing apoptosis and inhibiting cell migration and invasion [165,166,167]. '

Lastly regarding melatonin, in one small study it increased survival time of glioblastoma patients as discussed here :

karger.com/Article/Abstract...

Here is a relevant quote from the study :

' At present, no chemotherapy has appeared to influence its prognosis. On the other hand, recent advances in brain tumor biology have suggested that brain tumor growth is at least in part under a neuroendocrine control, mainly realized by opioid peptides and pineal substances. On this basis, we evaluated the influence of a concomitant administration of the pineal hormone melatonin (MLT) in patients with glioblastoma treated with radical or adjuvant radiotherapy (RT). The study included 30 patients with glioblastoma, who were randomized to receive RT alone (60 Gy) or RT plus MLT (20 mg/daily orally) until disease progression. Both the survival curve and the percent of survival at 1 year were significantly higher in patients treated with RT plus MLT than in those receiving RT alone (6/14 vs. 1/16). Moreover, RT or steroid therapy-related toxicities were lower in patients concomitantly treated with MLT. This preliminary study suggests that a radioneuroendocrine approach with RT plus the pineal hormone MLT may prolong the survival time and improve the quality of life of patients affected by glioblastoma. '

The above study was done in 1996 or 27 years ago, with no follow up studies in GBM patients despite the obvious benefits of melatonin as used in the study at only 20 mg/day. This begs the question of why more studies were not done in GBM patients using even higher dosing levels of melatonin which by the way has a very good safety profile that far exceeds any of the therapeutics regularly used to treat GBM. It is also very inexpensive and readily available.

To give you an idea of what higher melatonin dosing levels are capable of, the following study in Parkinson's disease patients used just 50 mg of melatonin per day of melatonin and this dose was able to reduce oxidative stress levels, a driving force in disease progression, to similar levels seen in healthy controls.

ncbi.nlm.nih.gov/pmc/articl...

A relevant study quote :

' At baseline, plasma levels of lipoperoxides, nitric oxide metabolites, and carbonyl groups in proteins were significantly higher in PD patients than in the healthy control group (Figures 1(a)–1(c), respectively). Conversely, the plasma activity of catalase was lower in the healthy control group than in PD patients (Figure 1(d)). These data suggest the existence of an active, persistent oxidative stress in PD. After three months of treatment with melatonin, the levels of lipoperoxides, nitric oxide metabolites, and carbonyl groups in proteins were lower than in the placebo group and were statistically similar to the levels of healthy controls. The activity of catalase was increased with the treatment with melatonin at levels similar to the control group. '

In ALS patients, melatonin was used at 300 mg/day for up to 2 years in a suppository form which is important because melatonin has poor bioavailability estimated between 3% to 15% and suppository delivery is thought to have significantly higher bioavailability :

onlinelibrary.wiley.com/doi...

Here is a relevant study quote :

' We found that melatonin attenuates glutamate-induced cell death of cultured motoneurons. In SOD1G93A-transgenic mice, high-dose oral melatonin delayed disease progression and extended survival. In a clinical safety study, chronic high-dose (300 mg/day) rectal melatonin was well tolerated during an observation period of up to 2 yr. Importantly, circulating serum protein carbonyls, which provide a surrogate marker for oxidative stress, were elevated in ALS patients, but were normalized to control values by melatonin treatment. This combination of preclinical effectiveness and proven safety in humans suggests that high-dose melatonin is suitable for clinical trials aimed at neuroprotection through antioxidation in ALS. '

Again this study was done in 2006, but it shows the safety of 300 mg of melatonin per day for up to 2 years.

In more recent years, Dr Shallenberger has stated using up to 360 mg of melatonin per day in his stage 4 cancer patients to good effect. In the following video link he is addressing a group of doctors explaining his use of melatonin in his patients as well as the various doses he is using :

youtu.be/Roh4lQXneQg(Not working as expected?)

Moving on, the next supplement I would like to discuss is Berberine. Like melatonin Berberine is able to cross the BBB and has a very good safety profile that certainly exceeds the safety profiles of the currently available treatments for GBM. There is certainly much less information available about Berberine and cancer than there is compared to melatonin and cancer, but berberine in recent studies is clearly showing it has multiple anticancer effects and like melatonin has shown synergy with some chemotherapeutics as discussed here :

e-century.us/files/ijcem/11...

Here is a relevant quote :

' Results: MTT assay results showed berberine inhibited cell proliferation of human breast cancer cell lines MCF-7 and MDA-MB-231 in a dose-dependent manner. Co-treatment with berberine and cisplatin or 5-Fu significantly inhibited cell viability of MCF-7 cells than that with berberine or chemotherapeutic drugs alone. Western blotting results demonstrated that the level of cleaved caspase-3 obviously increased in MCF-7 cells treated with berberine in combination with cisplatin than the monotherapy alone. Moreover, the ratio of Bax/Bcl-2 was upregulated in the group of combination therapy with berberine and cisplatin than that with monotherapy alone. Transwell assay data showed that berberine in combination with cisplatin significantly decreased cell migratory ability of MCF-7 cells. Conclusion: Berberine showed synergistic effects in combination with chemotherapeutic drugs to remarkably inhibit cell proliferation and suppress cell migration of breast cancer cells. "

This next review discusses some of the anticancer effects of berberine :

ncbi.nlm.nih.gov/pmc/articl...

Here is a relevant quote :

' The traditional Chinese medicine BBR has been shown to affect cell cycle, cell apoptosis, cell autophagy, and the tumor microenvironment. BBR has also been shown to exert anti-inflammatory and antioxidant effects. Tumor immunotherapy is a hotspot for tumor therapy in recent years, immune-suppressants such as PD-1/PD-L1 suppressants have emerged one after another. However, it is difficult to be widely used in clinic due to their high prices. BBR as an effective immunomodulator and a kind of cheap Chinese traditional drug, is expected to be widely used in clinical practice as an ideal drug for immunotherapy.

As studies showed, BBR exerted its role on autophagy through different mechanisms. In several cancer cells, BBR inhibited cell proliferation by inducing autophagy and also reversed drug resistance by regulating cell autophagy.45,46 However, in mature adipocytes, BBR maintained the cellular homeostasis by inhibiting autophagy.47 Studies showed that autophagy plays an important role in maintaining a stable intracellular environment.92,93 We inferred that autophagy plays different roles in cells. On the one hand, tumor cells evaded apoptosis through decreasing autophagy level; therefore, BBR treatment up-regulated autophagy and led to cancer cell death. On the other hand, BBR treatment lowered the original high level of autophagy in mature adipocytes to contribute to maintenance of a stable intracellular environment. Regulation of BBR on autophagy is complicated; therefore, studies are needed to make further progress on regulation of BBR on autophagy. '

I know, anticancer effects definitely, but what about for glioblastoma? This 2015 study points out one of the ways that berberine may be effective against glioblastoma :

aacrjournals.org/mct/articl...

Here is an important quote from the link :

' Our results showed that berberine possesses a potent antitumor effect against some glioblastoma cells. It can effectively induce glioblastoma cells to undergo cellular senescence. Interestingly, while berberine has been reported to exert its cytotoxic effect by inducing apoptosis in numerous types of cancer cells (13, 16, 18, 19), none of the glioblastoma cell lines we tested in this study showed signs of increased apoptosis in response to berberine treatment. Therefore, induction of cellular senescence is probably the major mechanism by which berberine exerts its antitumor effect against glioblastoma cells. Indeed, induction of senescence has recently been recognized to be an important therapeutic strategy for various types of cancer (25, 26). We further showed that the level of EGFR was greatly reduced in berberine-treated cells and that pharmacologic inhibition or RNA interference of EGFR similarly induced cellular senescence of glioblastoma cells. Accompanying the downregulation of EGFR, the RAF-MEK–ERK signaling pathway downstream of EGFR was remarkably inhibited in berberine-treated cells. Because the cellular senescence induced by berberine could be rescued by introduction of constitutive active MKK, we conclude that the induction of cellular senescence in berberine-treated glioblastoma cells is likely mediated by the downregulation of the EGFR–RAF–MEK–ERK pathway. Because EGFR amplification is characteristic of classic subtype of glioblastoma multiforme (GBM) and sustains the proliferation of GBM (27–29), the effective downregulation of EGFR by berberine suggests that use of berberine could be considered in the treatment of GBM. '

To further delve into berberine and glioblastoma, this 2022 abstract looks at various methods of action of berberine that work against glioblastoma and reaches the conclusion that berberine is a good choice for glioblastoma multiforme :

pubmed.ncbi.nlm.nih.gov/352...

Here is a relevant quote :

' The most typical malignant brain tumor, glioblastoma multiforme (GBM), seems to have a grim outcome, despite the intensive multi-modality interventions. Literature suggests that biologically active phytomolecules may exert anticancer properties by regulating several signaling pathways. Berberine, an isoquinoline alkaloid, has various pharmacological applications to combat severe diseases like cancer. Mechanistically, it inhibits cell proliferation and invasion, suppresses tumor angiogenesis, and induces cell apoptosis. The antitumoral effect of berberine in GBM is increasingly recognized. This review sheds new light on the regulatory signaling mechanisms of berberine in various cancers, proposing its potential role as a therapeutic agent for GBM. '

Unfortunately, the full study for the above link is behind a paywall.

Lastly, this final berberine/glioblastoma study goes even deeper into the methods of action of berberine against glioblastoma :

ncbi.nlm.nih.gov/pmc/articl...

Here is a relevant quote from the study :

' Berberine significantly inhibited the proliferation of human glioma U-87 cells, and induced apoptosis in the U-87 and LN229 cells by downregulating Bcl-2, and upregulating Bax and caspase-3. In addition, berberine also inhibited migration and invasion of the glioma cells. Furthermore, berberine exerted its effects on the proliferation, migration, invasion, and apoptosis of glioma cells by inhibiting the TGF-β1/SMAD2/3 signaling pathway, and exogenous TGF-β abrogated the pro-apoptotic and anti-oncogenic effects of berberine.

Conclusions:

Berberine inhibits glioma progression by targeting the TGF-β1/SMAD2/3 signaling pathway. '

So these are two supplements that you can discuss with your doctor and or oncologist given their very good safety profiles. I already talked a little bit about how melatonin might be dosed. '

Dosing of berberine in human studies show that 1500 mg/day in three divided doses of 500 mg each, one after breakfast, one after lunch and one after dinner has shown effectiveness and safety in people with diabetes as discussed here :

ncbi.nlm.nih.gov/pmc/articl...

Here is a relevant quote from the study of berberine in people with type two diabetes :

' In study A, 36 adults with newly diagnosed type 2 diabetes were randomly assigned to treatment with berberine or metformin (0.5 g t.i.d.) in a 3-month trial. The hypoglycemic effect of berberine was similar to that of metformin. Significant decreases in hemoglobin A1c (HbA1c; from 9.5% ± 0.5% to 7.5% ± 0.4%, P<0.01), fasting blood glucose (FBG; from 10.6 ± 0.9 mmol/L to 6.9 ± 0.5 mmol/L, P<0.01), postprandial blood glucose (PBG; from 19.8 ± 1.7 to 11.1 ± 0.9 mmol/L, P<0.01) and plasma triglycerides (from 1.13 ± 0.13 mmol/L to 0.89 ± 0.03 mmol/L, P<0.05) were observed in the berberine group. In study B, 48 adults with poorly controlled type 2 diabetes were treated supplemented with berberine in a 3-month trial. Berberine acted by lowering FBG and PBG from one week to the end of the trial. HbA1c decreased from 8.1% ± 0.2% to 7.3% ± 0.3% (P<0.001). Fasting plasma insulin and HOMA-IR were reduced by 28.1% and 44.7% (P<0.001), respectively. Total cholesterol and low-density lipoprotein cholesterol (LDL-C) were decreased significantly as well. '

One of the most common side effects reported from berberine in the study was gastrointestinal disturbance. Taking it after the meal may help prevent gastro upset.

So these are the two supplements that I wanted to mention as worth discussing with your doctor and or oncologist to see if they may be helpful for you or your loved one and to also make sure they will be safe with all that you or your loved one is taking.

Art

[Spinninghands123]

Thank you for sending this info!! I need to read it a few times to fully understand it, but I’ll definitely pay attention to what it says. 👍

[chartist in reply to Spinninghands123]

You're welcome!

There are only a few preliminary studies, but astaxanthin also might be a worthwhile consideration. It also has a very good safety profile as does berberine and melatonin. The trio might be useful adjunctive treatment that you can discuss with your doctor and or oncologist.

Dr. Lissoni studied melatonin extensively for decades with over 320 studies on PubMed dating back to the early 1980s right up to 2018. He found that just 20 mg of melatonin extended life beyond standard treatment in his glioblastoma patients. On the other hand, in more recent years, Dr. Shallenberger uses 180 mg up to 360 mg of melatonin per day in his stage 4 cancer patients as he discusses in this video where he is addressing other doctors to explain how he is using melatonin in his practice for cancer patients :

youtu.be/Roh4lQXneQg(Not working as expected?)

Art

[Spinninghands123 in reply to chartist]

Art,

Thank you again bunches for sharing this info!! I shared with my brother who is understanding more than I do and he is amazed at your information. I’m going to try all of it. ~Linda

[chartist in reply to Spinninghands123]

Glad to hear it , Linda!

Don't forget to discuss all of it with your doctor to make sure he or she agrees and to confirm that it will be safe for you and compatible with their treatment plan for you.

This study, that I didn't include in the original post because it is about a different form of cancer, shows that melatonin and berberine are synergistic against lung cancer :

ncbi.nlm.nih.gov/pmc/articl...

Here is a relevant study quote :

' Treatment with melatonin effectively increased the berberine-mediated inhibitions of cell proliferation, colony formation and cell migration, thereby enhancing the sensitivities of lung cancer cells to berberine. Melatonin also markedly increased apoptosis induced by berberine. Further mechanism study showed that melatonin promoted the cleavage of caspse-9 and PARP, enhanced the inhibition of Bcl2, and triggered the releasing of cytochrome C (Cyto C), thereby increasing the berberine-induced apoptosis. Melatonin also enhanced the berberine-mediated inhibition of telomerase reverses transcriptase (hTERT) by down-regulating the expression of AP-2β and its binding on hTERT promoter. Moreover, melatonin enhanced the berberine-mediated inhibition of cyclooxygenase 2 (COX-2) by inhibiting the nuclear translocation of NF-κB and its binding on COX-2 promoter. Melatonin also increased the berberine-mediated inhibition of the phosphorylated Akt and ERK. Collectively, our results demonstrated that melatonin enhanced the antitumor activity of berberine by activating caspase/Cyto C and inhibiting AP-2β/hTERT, NF-κB/COX-2 and Akt/ERK signaling pathways. Our findings provide new insights in exploring the potential therapeutic strategies and novel targets for lung cancer treatment. '

The point being that this synergy between melatonin and berberine is likely to apply to other forms of cancer.

Art

[HiggsOddysey in reply to chartist]

What dosage of berberine should be used and when and how should it be taken? Can you recommend a brand of berberine?

[chartist in reply to HiggsOddysey]

Berberine is often used by diabetics to help maintain glucose levels and HbA1c level, at a dose of 1500 mg/day in 3 divided doses of 500 mg each. 500 mg after breakfast, 500 mg after lunch and 500 mg after dinner. It is supposed to be taken before the meal in diabetics, but in people with sensitive stomachs, that can cause gastro distress. Taken after the meal can lessen this potential. Starting at one a day and working up over days to 3 per day can also help reduce the potential for gastro upset.

ncbi.nlm.nih.gov/pmc/articl...

Art

[Spinninghands123]

Hi Art,

I’m going to get melatonin powder instead of the capsules, and try taking up to 360 mg per day, since I’m in stage 4 Glioblastoma cancer. I thought it was interesting how Dr. Shallenberger said that every Melatonin inspector doesn’t take less than 100 mg. I will also get red lights, Berberine and Astaxanthin. I’ll keep researching all this info you wrote and shared. Thanks again! ~Linda

[chartist in reply to Spinninghands123]

Hi Linda,

I take 132 mg per night of melatonin myself for the multitude of potential health benefits that melatonin has shown in studies, but I generally mention to people that starting low and working up to higher dosing might be a safer approach. Unlike Dr. Shallenberger, I believe that some people do not tolerate melatonin in its oral supplement form. Melatonin made in the body is always tolerated and I did write a post about how to increase melatonin naturally for people who do not tolerate melatonin in supplement form.

I am also a believer in starting one supplement at a time for 2 weeks to a month to make sure you tolerate it. If you start everything at once and one thing does not agree with you, you will have to stop everything and start back with just one item anyway in order to find the offending supplement.

When I think of these three supplements Astaxanthin is the most tolerable for the most people followed by Berberine and then melatonin so starting in that order may be a consideration.

I also feel that vitamin D works well with melatonin and both can be gotten to some extent from the sun. At this point I would also like to point out that vitamin D is beneficial in terms of fighting glioblastoma and should be part of a healthful regimen.

The following study discusses vitamin D and its effects against glioblastoma :

li.uscap.org/article/S0023-...

Here is a relevant quote :

' Taking advantage of its endocrine function as a neurosteroid, vitamin D has become a target of interest to be used in conjunction with different chemotherapies. In this article, we review the mechanisms through which vitamin D and its analogs induce anti-tumor activity in glioblastoma, and the practical issues relevant to their potential application based on in vitro and in vivo studies. Vitamin D has largely been reported to promote cell cycle arrest and induce cell death to suppress tumor growth in glioblastoma. Glioblastoma cells treated with vitamin D have also shown reduced migratory and invasive phenotypes, and reduced stemness. It is worth noting that vitamin D analogs are able to produce similar inhibitory actions without causing adverse effects such as hypercalcemia in vivo. Upregulation of vitamin D receptors by vitamin D and its analogs may also play a role in enhancing its anti-tumor activity. Based on current findings and taking into consideration its potential cancer-protective effects, the clinical application of vitamin D in glioblastoma treatment and prevention will be discussed. '

If I was going to start taking these supplements myself, I would start with vitamin D and Astaxanthin at the same time because both are generally well tolerated, then I would add berberine and once I determined that I tolerated it, I would add melatonin. That is what I would do for myself and I do take all four of these supplements myself, but for their other potential health effects that they have shown in studies.

Art

[Spinninghands123]

Hi Art! I’m going to purchase all the info/items you and Dr. Shallenberger shared. Even red lights! 🤗

~Linda

[chartist]

Linda,

I sent another response to you with some suggestions a few minutes ago. You should run all of this by your doctor and or oncologist before starting any of it to make sure it will be safe and compatible with what they are doing.

Art

[Spinninghands123 in reply to chartist]

Hi Art,

I’m doing chemo and radiation, and will share the info with my oncologist on Thursday. I’ll let you know what he says. Really nice of you to talk about all of this.

~Linda

[chartist in reply to Spinninghands123]

Linda,

Melatonin has synergy with both chemo and radiotherapy and it helps to reduce the negative side effects of both. If compounded into a cream by a compounding pharmacy, it can help to ameliorate any skin burns from the radiotherapy and can help protect the skin in general.

The following study discusses how melatonin works synergistically with chemo :

ncbi.nlm.nih.gov/pmc/articl....

Here is a relevant quote :

' Chemotherapy is one of the most valuable treatments for cancer, but its clinical application is limited due to adverse side effects. Melatonin is a potent antioxidant and antiageing molecule, is nontoxic, and enhances the efficacy and reduces the side effects of chemotherapy. In this review, we first summarize the mitochondrial protective role of melatonin in the context of chemotherapeutic drug-induced toxicity. Thereafter, we tabulate the protective actions of melatonin against ageing and the harmful roles induced by chemotherapy and chemotherapeutic agents, including anthracyclines, alkylating agents, platinum, antimetabolites, mitotic inhibitors, and molecular-targeted agents. '

The following study discusses the synergy between melatonin and radiotherapy :

ncbi.nlm.nih.gov/pmc/articl...

Here are two relevant quotes from the review :

' Radiosensitizers are agents that increase the effect of radiation in tumor cells by trying not to increase side effects in normal tissues. Melatonin is a hormone produced mainly by the pineal gland which has an important role in the regulation of cancer growth, especially in hormone-dependent mammary tumors. Different studies have showed that melatonin administered with radiotherapy is able to enhance its therapeutic effects and can protect normal cells against side effects of this treatment. Several mechanisms are involved in the radiosensitization induced by melatonin: increase of reactive oxygen species production, modulation of proteins involved in estrogen biosynthesis, impairment of tumor cells to DNA repair, modulation of angiogenesis, abolition of inflammation, induction of apoptosis, stimulation of preadipocytes differentiation and modulation of metabolism. '

' All findings point to melatonin as an effective adjuvant molecule to radiotherapy in cancer treatment. '

This study from November 2022 exposing one more method of action by which melatonin fights glioblastoma :

ncbi.nlm.nih.gov/pmc/articl...

Here is a relevant quote :

' We analyzed melatonin’s functional effects on GBM proliferation, cell cycle, viability, stemness, and chemo-radiosensitivity. We then assessed the effects of melatonin on GBM metabolism by analyzing the mitochondrial and glycolytic parameters. We also measured the intracellular and extracellular pH. Finally, we tested the effects of melatonin on a mouse subcutaneous xenograft model. We found that melatonin downregulated LDHA and MCT4, decreasing lactate production and inducing a decrease in intracellular pH that was associated with an increase in ROS and ATP depletion. These changes blocked cell cycle progression and induced cellular death and we observed similar results in vivo. Melatonin’s cytotoxic effects on GBM were due, at least in part, to intracellular pH modulation, which has emerged as a newly identified mechanism, providing new insights into the oncostatic effect of melatonin on GBM. '

This last study discusses how Berberine works to improve the effects of temozolomide (TMZ) :

cancerci.biomedcentral.com/...

Here is a relevant quote :

' These findings demonstrate that berberine is an effective method of increasing the sensitization of GBM cells to TMZ treatment in a manner that is dependent upon the ERK1/2-mediated induction of autophagy, thus making berberine a potentially viable therapeutic agent for GBM treatment. '

Given the known historical outcomes from standard glioblastoma treatment, I hope your oncologist will have an open mind even though some of the studies are not optimal, as in randomized, double blind, placebo controlled trials. I think one very important point to always keep in mind when discussing these 4 supplements with your oncologist is that all 4 have better safety profiles than any medication they might use on you in the treatment of glioblastoma. All four supplements cross the blood brain barrier.

I will be very interested in what your oncologist has to say and other forum members may be interested too.

Art

[Spinninghands123 in reply to chartist]

Hello again Art,

I’ve been taking 20 mg of melatonin since last Sept, never been a problem. Last night I awoke at 2 am, so I decided to take another 20 mg. This made me extremely tired all day today, even took a two hour nap this afternoon, which is really unusual for me.

A day or two ago, you wrote: “Melatonin made in the body is always tolerated and I did write a post about how to increase melatonin naturally for people who do not tolerate melatonin in supplement form.”

I looked through all your posts, and didn’t see that particular post. Although, I did see where you mentioned a melatonin cream from a compounding pharmacy. Is that the post?

Thanks a bunch, Art!

~Linda

[chartist in reply to Spinninghands123]

Yes, this is what I was talking about regarding tolerating melatonin. One problem with taking melatonin so close to morning for the first time is that it can do what you described and a 20 mg jump was a big jump, double. That is why I mentioned that if I was doing this to myself, I would work my way up, which is what I did as I take 132 mg of melatonin every night. Even when I was already taking around 100 mg per night and went up to 120 mg per night, I felt tired for about a week or two the next day, but I adjusted to the new dose and tried to stay as busy as possible during the day, which helped . If I sat down and relaxed, I would usually fall asleep as you did. I had the same issue when I moved up from 120 to 132 mg per night. The next day tiredness lasted for about a week.

Yes, I did write a post about natural ways to increase your melatonin levels, but that can not take you to the levels that Dr. Shallenberger is describing or using. If you go back three of my replies to you, I talk about a specific order. This is what I said in that reply :

' If I was going to start taking these supplements myself, I would start with vitamin D and Astaxanthin at the same time because both are generally well tolerated, then I would add berberine and once I determined that I tolerated it, I would add melatonin. That is what I would do for myself and I do take all four of these supplements myself, but for their other potential preventative and health effects that they have shown in studies. '

All of the supplements have shown some abilities to fight glioblastoma, so I was mentioning starting the Astaxanthin together with vitamin D because these two are generally well tolerated. I mentioned melatonin as last because I know that some people do not tolerate it or take a while to adjust to higher dosing and I also mentioned going over everything with your oncologist first to be safe and to make sure it is all compatible with what the oncologist is going to do and use. I am not a doctor and there is a limit to what I can say to you. I can not give you medical advice, I can only relate what studies show in terms of these supplements and my own experience from an anecdotal point of view.

Another consideration is doing a phone consult with Dr. Shallenberger as the video I linked to was done about 5 years ago and he may know more now about how to make melatonin more tolerable for you or as he said the pure powder form may be a better option. If you want to consider that option, his contact information is on the web. As far as the next day tiredness, you may have to weigh that against what you are trying to fight. I also recommend watching his video again as I remember when I watched it the second time, I picked up much more of what he said, that I didn't catch the first time.

Art

[Spinninghands123]

Hi Art!

I talked to my oncologist, although I’ll admit it’s hard to get him to answer questions. He did say that Melatonin is ok, but go ahead and take it if it helps me to sleep. He did like Berberine, and said he takes it himself. He said he doesn’t like Astaxanthin, but wouldn’t tell me why.

I sent an email to Dr. Shallenberger, hopefully I’ll hear from them next week.

~Linda

[chartist in reply to Spinninghands123]

Linda,

Okay, he is good with melatonin and berberine and I will assume he is good with the vitamin D because who is against vitamin D? So that's 3 out of 4, not bad! Admittedly the studies for astaxanthin are not strong by comparison, but there are a few such as this one :

ncbi.nlm.nih.gov/pmc/articl...

Here is a relevant quote :

' Specifically, astaxanthin and adonixanthin showed an ability to suppress cell proliferation and migration in three types of glioblastoma cells. Furthermore, these compounds were confirmed to transfer to the brain in a murine model. In the murine orthotopic glioblastoma model, glioblastoma progression was suppressed by the oral administration of astaxanthin and adonixanthin at 10 and 30 mg/kg, respectively, for 10 days. These results suggest that both astaxanthin and adonixanthin have potential as treatments for glioblastoma.'

If you converted this dose to human dosing, the astaxanthin would be under 100 mg per day and astaxanthin seems to be very well tolerated in studies.

Congratulations on having your oncologist agreeing to you using these supplements!

Art

[Spinninghands123]

Yes, he saw my note with all 4 supplements, and didn’t even say anything about Vitamin D, so that’s obvious it’s not a problem. Thanks for all the info, I’m in the process of purchasing many things, and feeling excited that everything may help.

~Linda

[chartist in reply to Spinninghands123]

Very good on all of it, Linda!

Neuroinflammation is a side effect of the treatment process of radiotherapy as mentioned in this 2022 study :

ncbi.nlm.nih.gov/pmc/articl...

Here is a relevant quote :

' High radiation doses are therefore delivered to large brain volumes and are known to extend survival but also cause delayed toxicity with 50%–90% of patients developing neurocognitive dysfunction. Emerging evidence identifies neuroinflammation as a critical mediator of the adverse effects of RT on cognitive function. '

Fortunately, astaxanthin, berberine and melatonin all inhibit neuro inflammation, but I am not including studies here in order to keep this short. Keep me updated!

Art

[chartist in reply to Spinninghands123]

Linda,

Here are links to the studies I mentioned showing that Astaxanthin, Berberine and Melatonin all fight neuroinflammation. Both radiotherapy and chemotherapy cause neuroinflammation. In the case of chemotherapy, it is sometimes referred to as "chemobrain".

Astaxanthin :

ncbi.nlm.nih.gov/pmc/articl...

A relevant quote :

' Mounting evidence has revealed that astaxanthin is neuroprotective and has therapeutic potential by inhibiting neuroinflammation, however, its functional roles and underlying mechanisms in modulating neuroinflammation have not been systematically summarized. Hence, this review summarizes recent progress in this field and provides an update on the medical value of astaxanthin. Astaxanthin modulates neuroinflammation by alleviating oxidative stress, reducing the production of neuroinflammatory factors, inhibiting peripheral inflammation and maintaining the integrity of the blood-brain barrier. Mechanistically, astaxanthin scavenges radicals, triggers the Nrf2-induced activation of the antioxidant system, and suppresses the activation of the NF-κB and mitogen-activated protein kinase pathways. With its good biosafety and high bioavailability, astaxanthin has strong potential for modulating neuroinflammation, although some outstanding issues still require further investigation. '

Berberine :

frontiersin.org/articles/10....

A relevant quote :

' The above evidences suggest that berberine has various roles in neurological diseases, including neuroinflammation, neuroprotection, oxidative stress, etc. '

Melatonin :

ncbi.nlm.nih.gov/pmc/articl...

A relevant study quote :

' Conclusively, the overall findings suggest that melatonin may reduce brain injury-induced neurodegeneration by regulating oxidative stress, neuroinflammation, autophagy, and apoptotic cell death. '

Art

[Spinninghands123]

Hi Art!

I’m now taking the Berberine after meals, and my body seems to be fine with it. I want to increase my melatonin, but I’m too chicken as of yet. Going to order the Astaxanthin and also powdered melatonin. Do you take powdered melatonin instead of the capsules?

~Linda

[chartist in reply to Spinninghands123]

I'm glad that you are tolerating the berberine! Powdered melatonin is fairly bitter and may not be that easy to take for many people. I have powdered melatonin, but use it for other types of applications. Did you see my reply regarding radiation to the brain? Keep me updated on how everything is going.

Art

[Spinninghands123]

Hi again!

I re-read everything you sent and wrote, and your only reply I saw about radiation to the brain is that it causes neuro inflammation. Is that what you’re asking me about? I just finished 4 weeks of chemo and radiation, and I’m doing pretty good. I now have some pain in my elbows and shoulders occasionally, and a little bit of a bloody nose. Also lost some hair where my surgery scar is. Not a big deal to me. I see the radiation therapy doctor tomorrow, so I’ll ask him if he knows what’s causing them. I’ll even ask him about the melatonin, Berberine and Astaxanthin, although I doubt he’ll say anything about them. (I’ll let you know if he tells me anything). The Berberine still seems to be comfortable to use so far. I’m waiting until I’ve been using it for 2 weeks, (as you mentioned) before I start taking Astaxanthin. 🤗

Thanks again! ~Linda

[chartist in reply to Spinninghands123]

Yes, that was it.

It's good that you were on the 20 mg melatonin as it helps reduce the damaging effects of C&R and it makes them more effective while adding all of its anticancer effects. More would have been better, but as you said, you're doing pretty good.

Great that you've added the berberine. If you're not having even a little gastro discomfort, you might consider adding the astaxanthin a bit sooner as it is generally well tolerated. Don't forget vitamin D with the astaxanthin! I didn't realize you were already doing C&R, in fact I was going to ask you when you were starting it.

I will be interested in hearing what your radiation therapy doctor has to say. It completely baffles me why melatonin is never mentioned by doctors dealing with cancer. If they are staying up to date on cancer studies, how can they not be recommending melatonin to all of their patients?

Art

[Spinninghands123]

Good morning, Art!

I had another radiologist meeting this week and he said to ask my oncologist questions about the pain I’m having. My shoulders and elbows now hurt a lot when I wake up, but then I exercise them, and they aren’t as painful throughout the day.

My astaxanthin will be arriving, today! I also got a hydrogen generator bottle and adding oxygen to my water. I hope it helps.

Regarding your last question, I guess most doctors are too busy to research supplements such as melatonin. 🤷🏻‍♀️

I’m trying to set up an appointment with Dr. Shallenberger whom you mentioned. I’ll be sure to keep you updated.

~Linda

[chartist in reply to Spinninghands123]

Linda,

Regarding the pain in your shoulders, I can make two suggestions.

The first one is magnesium chloride oil, commonly called mag oil and available in vitamin stores and most online supplement suppliers. You just spray it on and rub it in to your shoulder joints. Here is a typical product on Amazon :

amazon.com/Magnesium-Oil-Sp...

The second one is an easy to apply roll on pain reliever called Stopain and it is available at most Walgreens and Walmarts. It is one of the most potent topical over the counter pain relievers available. It is also available at Amazon. Here is a link to it :

amazon.com/Stopain-Extra-St...

Stopain is a more potent pain reliever than mag oil, but mag oil can also stop cramping in about a minute. Since you are only complaining about shoulder pain, I would start with Stopain and see if it is effective enough to relieve your pain. Neither of these products has a strong smell. Stopain has a smell to it, but it dissipates in 5 minutes or less.

I think it might be more prudent to go with this topical approach because the chemo and radiation are essentially poison to your body, and it might not be the best idea to take an oral pain reliever like Tylenol or stronger because Tylenol can be harsh on the liver and you don't want to add to the toxicity that your body is already dealing with.

On a related note, this article about joint pain and cancer may interest you :

cancer.net/coping-with-canc....

Here is a relevant quote from the article :

' Some cancer treatments can cause joint pain. Often, pain goes away after treatment. In some cases, joint pain can be a late effect, which means it occurs months or years after cancer treatment ends. '

Keep me posted!

Art

[chartist]

To add further evidence to show how certain supplements can have synergy against colorectal cancer (CRC), this new study shows that the combination of Andrographis and Berberine have significantly more anticancer effect in colorectal cancer than either supplement alone as described in this study :

ncbi.nlm.nih.gov/pmc/articl...

Here is an important study quote that describes this synergistic effect against CRC :

' Taken together, our data revealed the powerful enhanced synergistic anti-CRC effects of berberine and Andrographis and provide evidence for the combinational targeting of DNA-replication-related genes as a promising new strategy for the therapeutic option in the management of CRC patients. '

Further, the graph below clearly illustrates this synergy at fighting CRC showing a significant reduction of tumor volume as well as tumor weight as shown by the blue bars and lines. The synergy between these two supplements is very significant.

Both of these supplements have studies to support their anticancer activities, but clearly they are significantly more potent together when it comes to CRC. Although this new study is about CRC, both berberine and andrographis cross the blood brain barrier and both have shown activity against Glioblastoma.

Art

Synergy between Andrographis and Berberine in reducing tumor volume and tumor weight.

[chartist]

Hi Linda,

It's been over a month since you last updated and I was wondering if you have a current update to share?

Art

[Spinninghands123]

Hi Art,

I just saw your last note to me. I’m so sorry I didn’t find it earlier, and I haven’t responded. I did do well on my MRI, my oncologist didn’t show up (he’s moving), but a couple of PhD RN’s were there. They looked at my MRI and seemed to honestly express that my tumor has shrunk a bunch, and they feel I’ll be losing it. They were amazed, and even said they never see such a good MRI with anyone else.

The only problem I am having was a bladder infection I’ve had for weeks. It seemed the cranberry juice I was drinking was helping, but then it got so bad last week, I went to the hospital. They gave me an antibiotic to take for a week, I’m hoping it will make my bladder heal.

I also have water behind my eardrums. The doctors suggested I not have holes poked, because it might cause an infection near my brain tumor. I am totally Deaf because of it. Can’t even hear a door knock.

I’ve been taking all the pills you recommended, and also taking some pills I got from Mexico. I may be taking curcumin IV’s soon, as well as going to Canada for heat therapy. I can’t remember a lot of names and words, my memory has gotten worse since chemo. I now take it one week a month.

I hope this is helpful.

~Linda

[chartist in reply to Spinninghands123]

Wow Linda, that is very fantastic news!!! Thank you for the reply and yes, definitely helpful!

I am very happy for you and I am glad your plan is working! These results seem very positive and very quick as I only posted those supplements 2 1/2 months ago and I know there was a delay before you got them and actually started using all of them. I know the nurses told you that the tumor had "shrunk a bunch", but it would have been nice if they gave you the actual dimension changes of the tumor for a reasonable comparison to what it was before. If it is shrinking this fast, do you want to add other remedies? Sometimes too many can, start to work against each other and have bad interactions.

Did you add the Andrographis to your regimen? I linked to that CRC study that shows that it and melatonin have significant synergy together and both cross the blood brain barrier. If you didn't add it, it definitely seems worth considering because of that potent synergy with melatonin. That is a very interesting study and the graphs are very impressive and show just how potent the synergy between the melatonin and andrographis is.

When you have time, can you let me know what the doses of everything that you are taking is?

Regarding the UTI, I make a drink that has been very effective and significantly more so than just cranberry juice and it doesn't have the potential side effects of the antibiotics which can be very significant. If started at the first signs or symptoms of a UTI it can reverse it rapidly. If you are interested in that, let me know and I can send the info on how to make it. Did they let you know what the offending bacteria is? E coli. is the most common, but there are others.

The problem with UTIs under your current state is that they can make everything worse and cause severe brain fog issues when you are having radiation and chemo done also. These are generally temporary, but there are many supplements that you can take to reduce brain fog. Melatonin, berberine, astaxanthin, andrographis and vitamin D would be on that list.

Regarding the brain fog issues, getting rid of the UTI is the first step. You didn't say how much of the tumor is left, but once it is gone you can be more aggressive in treating the fluid buildup around the ears.

Linda, would it be okay with you if I write about your experience on another health forum? I won't mention your name.

I look forward to your updates, Linda and continued success to you in implementing your plan!

Art

[Spinninghands123 in reply to chartist]

Hi Art!

I'm not at home this weekend (having a bunch of fun). But when i get home ill write you all the info, definitely.

One think ill mention, now. I researched info about Radon and brain cancer. Found articles about a couple of scientists (in VA) who figured out that over 140 people got some kind of brain cancer (yes, glioblastoma, also).

So i went to Home Depot and got a little radon test and put it in my basement. When i get home, ill send it to the lab that will test it.

Yes you can share whatever ive written with whoever you want. I should mention that i was taking only the herbal supplements (and others) as you suggested, and i didnt start the tablets from Mexico until AFTER the MRI. I think i will be getting another MRI in about a month from now.

Ill write again very soon.

~Linda

[chartist]

Thank you, Linda, I look forward to those answers and updates!

Art

[chartist in reply to chartist]

Linda,

It has been a week and I was hoping you would have been able to reply by now, but since you haven't, I want to make sure you are aware of something that may be of significant importance for you. You had mentioned that the two nurses had told you that the tumor 'had shrunk a bunch'. You also mentioned that you added the pills you got from Mexico after you had the last MRI done and also planned to add two other treatment modalities to your regimen.

If the nurses were correct about the tumor shrinking a bunch and you add other treatments that might cause even more and faster tumor shrinkage, that could be dangerous if the tumor shrinks too much too fast as the sanitation system of the brain has to properly dispose of the breakdown products from the tumor and if the sanitation system is not able to dispose of the debris in a timely manner, this could cause inflammation and swelling of the brain and that could be very dangerous.

Your last oncologist may not have mentioned that potential to you about rapid tumor shrinkage and potential complications from such shrinkage because it would not be the most common occurrence in glioblastoma. You would do well to discuss this issue with your new oncologist and or doctor or medical care professional as soon as possible and before you add anymore adjunctive treatments to your regimen and I cannot emphasize the importance of this for you enough.

Art