Lung

There are some remarkable recent studies here on use of natural supplements, over the counter drugs and more that can substantially improve quality of life for patients, including slowing progression. Strikingly, these are similar to or better than trials with new oncology drugs in many cases. Some are even very simple, and all are easily available and well proven.

With immunotherapy drugs such as pembrolizumab (Keytruda) or nivolumab (Opdivo), new research reports large improvements in responses with use of antihistamines such as loratadine. Both for NSCLC adenocarcinoma/ squamous cell and for SCLC. The substantial risk reductions have resulted in average increase of 80% to the treatment reponse in real terms, and a less than half the incidence of serious side effects from the drugs. Importantly, H2 class antihistamine cimetidine substantially increased patient risks by nearly 2.4X due to negative effects on gut bacteria, the microbiota.

A 2021 trial of astragalus extract with chemotherapy or tyrosine kinase inhibitors such as erlotinib reports really positive impacts. Astragalus is a widely available and very well proven herbal supplement. Remarkably, for the 3/4 majority “low PDL-1” patients, roughly halved the risk of progression. This is equal to the effects of adding immunotherapy to chemotherapy, but with much lower side effects. The data from this real world Turkish trial confirms the activity of astragalus extracts beyond asia, and that builds confidence for similar well proven herbal supplements especially danshen. Based on the patient records of lung cancer patients treated in Tiawan, an aggregated analysis of trials shows nearly two thirds overall risk reductions for patients that took sustained doses of danshen. Immune system enhancing actions of astragalus and danshen may be something to avoid following transplant surgery though. A similar 2021 study on the same database found a 21% risk reduction for use of low dose aspirin, which like astragalus and danshen show strong indirect evidence of anti-metastatic activity playing a key role in assisting treatments.

In asian oncology, mushroom extracts from Turkey Tail are also widely available and well proven due to their “beta glucans” – active compounds that activate the immune system . A study averaging results from eleven asian trials reports some average impacts that can be substantially beneficial especially in early stages. Including easing many side effects. Also in early stages, correcting vitamin D3 has been shown to have a large benefit to the results of treatment for about a quarter of cases, and that was only 1200IU doses. The proposed mechanisms include lowering metastatic activity.

Multiple studies of patient outcomes have reported some much higher response rates in users of statins, including in relation to immunotherapy. The risk reductions with statins are substantial, and atorvastatin is highlighted though lovastatin, and therefore red yeast rice, are closely performing alternatives. Its remains unclear to what degree these benefits would transfer across all patients, but research indicates likely impacts are in those who respond with lower cholesterol levels.

Melatonin has been heavily studied in several cancer types and shows valuable improvements in outcomes, including substantially improved symptoms in dyspnea – shortness of breath. Surprising for its impact in very late stage patient care. Clinical trials have been run at both 100mg and 1000mg in various cancers with reports showing many patients responding in advanced stages including some with surprising stabilization of disease progress.

Recent studies of immunotherapy outcomes also show the need for a healthy gut microbiome in particular a natural 3-5% of akkermansia. Patients with low levels had much weaker response rates and higher risks for faster progression. Crucially though, over-abundance due to exposure to antibiotics caused accelerated progression. Along with these bacteria strains, the presence of inosine both naturally and supplemented has growing evidence of strongly improving the response rates of immunotherapy. Related to diet, there are some promising results for long term remission is some patients using ketogenic diets (see Lifestyle) and there are ongoing trials including for immunotherapy. Some strong “responders” get sustained long term benefit.

Also in immunotherapy, circulating ferritin indicating irregular iron levels is linked with 60% increased risks for progression. A milk pre-biotic lactoferrin can bind iron and reduce ferritin levels, and has its own clinical studies showing improved outcomes. Another biomarker indicating lower risks are circulating levels of a fatty acid type, medium chain acylcarnitines. Urolithin-A, a supplement derived from pomegranate or walnuts, has been shown in anti-aging science to help reduce levels, improving metabolic health.

High serum levels of copper especially with insufficient selenium is very much linked with a poor prognosis. The reason is not clear, but one possibility is cancer switches the metabolism to free up copper already in the body, which it needs to grow and spread rapidly. And, low selenium is commonly also reported, which weakens immune system defenses. Heavy metal detoxification has been shown in patient case with use of citrus pectin, ideally with marine alginates. Citrus Pectin also limits the so called galectin-3 signaling pathway which has been shown in treatment resistance in lung cancer oncology, especially immunotherapy. In kidney cancer, “high” dose selenium has been shown to allow oncology drugs to penetrate tumors much more effectively, and has ongoing clinical studies.

Systemic inflammation is linked with increased risks for progression, especially in later stages. Both acute type inflammatory responses measured by c-reactive protein, and immune system related neutrophil-to-lymphocyte ratios. Maintaining relatively lower levels of both make a substantial difference. Astragalus also has evidence of improving immune system balance during immunotherapy for lung cancer, and NLR while curcumin and other other functional foods including garlic can help bring down CRP. Another nutrient recently seen boosting natural immune system activity during immunotherapy is sodium, higher levels are almost exclusively linked to complete treatment response.

The so called Th1/Th2 immune system balance is strongly linked to the progression and to treatment resistance. Molecular iodine solutions are emerging in this area in breast cancer management and seen boosting Th1 anti tumor activity and helping suppress over active Th2 used in resistance. The has improved results in surgery plus chemotherapy and may support increased response immunotherapy (see Supplement Library). Its also relevant that AM immunotherapy is more effective than PM/evening in other cancers.

Beyond statins, the beta blocker landiolol has shown some considerable promise based on lung cancer case histories (see Repurposed Drugs)

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Antihistamines have very broad evidence of effects in lung cancer

Relative overall risk reductions result in an average of 80% longer overall responses
Even larger effects in relapse or spread with a 3X longer average time free of progression
Serious Adverse Events rate drastically reduced to about a fifth, including major organs

This study showed that the concurrent administration of H1 antihistamines and immunotherapy is associated with enhanced survival benefits and prolonged progression-free survival (PFS). In contrast, the concurrent use of H2 antihistamines is associated with reduced PFS and overall survival (OS) in patients with lung cancer. Histamine and H1 receptors play a crucial role in the tumor microenvironment. Concomitant use of antihistamines and immune checkpoint inhibitors (ICIs) may enhance the effect of ICIs. Concurrent administration of H1 antihistamines and immunotherapy is associated with enha...

Astragalus actions include protecting and balancing immune responses often with clear effects reported

Adding astraglus supplements to medical treatment more than doubles its effect
The overall relative risk reductions reported here are at 54% and a lowering of side effects
Compared with other oncology drugs, the TKI erlotinib showed the best outcomes in this trial

Our data also showed that AMe [astragalus] increases OS [overall survival] despite different types of regimens, though this may be because near all of our patients used cisplatin doublets [chemo]. As with CT, Astragalus and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have an additive effect on EGFR mutant lung cancer, according to current literature. Consistent with these data,our results showed survival advantages of AMe in combination with erlotinib or CT. Although our population is relatively low, it may be a key population since other studies held in Asian countri...

Danshen evidence from patient records is compelling in both cancer and vascular health

Up to 64% longer overall response is reported in those adding danshen to oncology
Patients who took danshen extract > 12 weeks saw highest benefit, longer use is better
As a side note, the choice of carboplatin for chemotherapy saw better outcomes than alternatives studied here

Collecting together, this is a novel model demonstrating that danshen has protective efforts for the advanced lung cancers patients in Taiwan through the data of NHIRD [national patient records database] . DT [from danshen] inhibit the migratory ability and the macrophage recruitment ability of lung cancer cells…DT might be a novel anti-lung cancer agent and further prospective randomized study is warranted to validate this finding.,,,On the multivariate Cox model the use of danshen remained highly associated with decreased mortality (the adjusted HR of danshen users who had used �...

Aspirin has a majority of analysis in its favor including all-cause risks

Analysis on national scale case records for benefits of aspirin use
Results show on average a one third absolute increased result
Reported relative risk reduction levels were 21% for any use >1 month

The results of our study suggest that among inoperable NSCLC patients, aspirin use is associated with an improved OS [overall survival]..A meta-analysis of three randomized trials that were originally conducted for the prevention of vascular events, reported that a comparison of aspirin versus a placebo showed that aspirin was protective with regard to lung mortality , which is consistent with the result of our study, which showed that aspirin use is associated with an improved OS in inoperable NSCLC patients. Using a big data analysis approach, our study provided further evidence in suppor...

Turkey tail extract restores immune reaction to tumor cells especially in digestive tract cancers

Analysis across multiple lung cancer research studies on Turkey Tail with chemotherapy
Reduced progression risks up 40% for early stage cases, especially with sustained use
Frequently reported as reducing side effects of chemotherapy

These results suggest that PSK [Turkey Tail mushroom extracts] may significantly improve immune function, tumor-related symptoms, and survival in patients with lung cancer, when used as adjunctive therapy alongside or following standard chemotherapy or radiation therapy, or surgery. PSK appears to increase the tolerability of chemotherapy and reduce limiting factors such as bone marrow suppression, while improving long-term survival. PSK appears to be effective particularly among patients with earlier stages of disease, and has been shown to significantly improve survival among patients wit...

Vitamin D3 and its immune system health actions are key, higher doses being trialed in oncology

Specific research on EFGR mutated lung adenocarcinoma the most common grouping
More than 1/3 risk reductions by having sufficient D3 levels, similar results for many cancers
Most patients in this group, about a quarter of all cases, were deficient at diagnosis

Patients who were 25(OH)D3-sufficient [i.e vitamin D3 level in the blood] experienced significantly longer benefit from EGFR TKI therapy (mean 14.5 months) than those with 25(OH)D3 insufficiency (mean 10.6 months). In contrast, 25(OH)D3 had no prognostic value in patients with KRAS-mutant LUAD that received cytotoxic chemotherapy…. We conclude that vitamin D sufficiency portends increased PFS among EGFR-mutant LUAD patients that receive EGFR TKIs, and that vitamin D signaling maintains drug efficacy in this specific patient subset by opposing EMT.

Melatonin trials have shown longer survival rates, even in late stages, and improved side effects

2021 study in melatonin shows crucial need for evening doses, and here at moderate 20mg
There is a large effect in slowing progression, with around a 40% risk reduction
Strikingly important benefits in side effects, including improved ease of breathing

The multivariate analysis found no survival benefit among AM melatonin patients, but PM melatonin patients experienced a reduced risk of death of 39%, which is clinically significant. The greatest survival benefit occurred among the PM melatonin arm patients who reported normal quality sleep at baseline. Two PSQI components, sleep quality and sleep efficiency, had large effects on patient survival, wherein sleep quality decreased the hazard rate of death by 46%, while sleep efficiency elevated the hazard rate of death by 40%….Moreover, PM melatonin’s therapeutic effect was optimal i...

Red Yeast Rice or where possible a prescription statin have multiple beneficial actions including all-cause risks

2022 analysis across mutiple studies on benefits with statin use
Reported risk reducing effects of these statin case studies from 30 to 60%
Lovastatin found in red yeast rice averaged 50% better relative risk level

Based on this real-world evidence (RWE), we found that atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin and simvastatin were associated with a 50% reduced overall risk for developing cancer… The effect of atorvastatin (OR 0.3) exceeded other considered statins, even after exclusion of aspirin as the strongest confounder (OR 0.63). Additionally, we note that those patients taking statins have a 38% decreased risk of death (HR 0.64)….For patients taking statins, we calculated a higher probability of surviving cancer versus subjects who were not taking any statins (...

Akkermansia gut bacteria levels are becoming a key marker of improved response in oncology, especially immunotherapy

Good natural levels 3-5% increase immunotherapy response 50 to 100%
Relative increases in overall survival rates can be boosted up to 80%
Antibiotics heavily implicated in dramatic worsening of outcomes

These differences were even more marked in the individuals that received immunotherapy alone as first-line therapy (ORR of 41% versus 19%). Besides, the relative abundance of A. muciniphila presented higher predictive efficacy for OS than PD-L1 expression…A crucial point to take away from this study is that antibiotics significantly decreased the OS in NSCLC, independently from A. muciniphila status…Individual baseline gut microbiota profiling may represent promising biomarkers to predict ICIs reponses as well as immune-related adverse effects. Understanding and addressing the s...

Lactoferrin can provide a healthy balanced iron level

Absolute results from oncology treatments improved about a quarter
A similar size of effect is reported for the slower progression rate
Reduced serious chemotherapy side effects around a fifth

[Lactorferrin during chemotherapy] demonstrated an apparent improvement in RR, PFS, and OS in patients with previously untreated stage IIIB/IV non-small cell lung cancer and appears to enhance activity without significant additional toxicity..Other major groups of AE [adverse events or side effects] reductions included areas where lactoferrin has been shown to have protective effects: (i) hematological; (ii) GI, specifically relating to diarrhea, loose stools, and vomiting; and (iii) musculoskeletal/neurosensory. As an immunomodulatory agent, lactoferrin has demonstrated acceleration in the...

Beta glucans protect and balance immune system activity improving outcomes

Shitakke mushroom extract, lentinan, improves chemotherapy results in lung cancer
Objective Response Rate for instance the size of tumor regression, was 31% higher
There is a substantial reduction in the probability of drug related side effects

Twelve clinical studies of lentinan (mushroom beta glucan) injection combined with chemotherapy in the treatment of NSCLC with 458 controls and 492 NSCLCs patients were finally included in this meta-analysis. The pooled results indicated that the objective response rate was significant improved in the lentinan [from shitakke] injection combined chemotherapy group compared with chemotherapy group only..The chemotherapy-related toxicity of III/IV gastrointestinal reaction and III/IV granulocytopenia were significant decreased in the combined group

Selenium is developing in kidney and ovarian cancer, high doses pulsed with oncology drugs

Better results with faster improvements in selenium levels during radio therapy
A large beenfit, up to 70% relative risk reductions in advanced stage NSCLC
Active supplementation trials with “high” doses are showing a lot of promise in other cancers

The change in selenium levels between the start of treatment (t0) and the first timepoint after treatment (t1) was statistically significant in terms of the patients’ overall survival for the whole study cohort (models I–III); likewise, the patients with increased serum selenium levels during radiotherapy had the best OS. In addition, significant associations with OS for the baseline selenium value t0 in patients with non-metastasized NSCLC were found. The changes in serum selenium between t0 and t1 (models I, III, IV) and also between t0 and t2 (models I–IV) were significant in terms...

Citrus Pectin removes heavy metals such as copper and has its own anti-cancer mechanisms

Relatively high copper levels accelerate disease progression, including lung cancer rates
Analysis for 5 year here shows 50% lower progression rate with relatively lower copper levels
Citrus Pectin binds copper, removing it from circulation, and also has significant anti-cancer actions of its own

.. a higher serum Cu level, Cu:Zn ratio, and whole blood Zn level were shown to negatively affect all-cause mortality risk in lung cancer patients. However, further, more detailed, and with a larger cohort studies on the role of Cu and Zn status in predicting all-cause and cancer-cause mortality among lung cancer patients as well as studies on mechanisms underpinning surprising negative prediction of lung cancer survival in patients with elevated whole blood Zn status are warranted. This could be helpful in developing strategies to improve the outcome of patients with regard to the body sta...

Oat and egg based functional foods are entering early stage clinical trials for several cancers

Those with lower internal tumor fluid pressure have slower progression and higher treatment responses
Recurrence free levels were 84% at four years vs 70% with those with relatively high pressure
The tumor fluid pressure increases with tumor size, and growth markers

Interestingly, the low IFP [tumor internal fluid pressure] group (IFP ≤7.4 mm Hg) showed better recurrence free survival than the high IFP group (IFP >7.4 mmHg). Although multivariate analysis did not select IFP as independent prognostic factor, subgroup analysis of the patients with adenocarcinoma selected IFP as independent prognostic factor. These results, as well as those of the previous reports in other types of cancers,4–7) support the use of IFP as a candidate novel prognostic factor for lung cancer….Moreover, IFP was found to correlate with the Ki67 index [the rate of t...

Urolithin A has actions that may help reduce cancers upregulated fatty acid metabolism

Abnormal fatty acid metabolite levels increase risk of treatment side effects and failed treatment
Low levels of certain so called medium chain acylcarnitines predict decreased risk overall
Reaching lower levels could halve risks of progression based on the data here, with no downside

There are lots of studies reported that patients with lung cancer with irAEs had better OS and PFS, but our study showed the reverse result that patients with irAEs had worse OS. This might be the reason that patients who had irAEs in our study discontinued immunotherapy, which affected the clinical treatment and OS of patients. However, patients with mild irAEs would continue to receive immunotherapy and benefit from the treatment. We found that levels of decenoylcarnitine (AcCa(10:1) 2, decenoylcarnitine (AcCa(10:1) 3, and hexanoylcarnitine (AcCa(6:0) at baseline plasma were related to OS...

Curcumin has evidence for reducing levels of systemic inflammation used by cancers

Relatively lower systemic inflammation strongly indicates improved responses
All types of NSCLC show this link but even more in EFGR mutated types
Low inflammation measure by CRP can more than halve the progression risks

CRP level is used as a regular prognosis test, but it is a good prognostic factor only under the following conditions: (I) the cancer subtype is adenocarcinoma and (II) the treatment approach used is chemotherapy. Even if EGFR-TKI, which has a very strong therapeutic effect, is used, CRP alone can predict the therapeutic effect and prognosis…High CRP levels predicted a lack of response to treatment in patients with advanced lung adenocarcinoma with or without EGFR mutations… Especially for high serum CRP levels can be expected shorter PFS and OS. This tendency was present even ...

Sodium is recently emerged as a standalone biomarker for immunotherapy response

Recent data from immunotherapy results shows crucial need for sodium
Complete responses to therapy almost exclusively in those with relatively high levels
Sodium is suggested to increase natural immune system activity during treatment

This study highlights that ICI-treated patients with higher sodium levels had significantly better OS, PFS, and anti-tumor responses. Baseline serum sodium levels could be cost-effective and valuable predictive biomarker for ICIs across diverse tumor types and ICI agents….Multivariate analysis revealed that serum sodium levels between 135–140 mmol/L were an independent predictor of improved OS (HR: 0.58) and PFS (HR: 0.76; 95%CI: 0.58–0.99) and those with levels > 140 mmol/L had an even lower HR of 0.43 for OS [overall survival]

Inosine trials are few but some early promise with immunotherapy

Inosine supplements increase immunotherapy responses by reducing resistance
Pilot trial in several cancers show slower progression and lower side effects
Here the overall risk for progression is reduced 37% and by a half for lung cancers

In terms of safety, Grades 3 and 4 adverse reactions were observed in 25 (29%) and 31 (36%) patients in the inosine and non-inosine groups, respectively, and inosine likely reduced immunotherapy-related adverse reactions. The results of this trial suggest that, compared with that in the non-inosine group, the mPFS was significantly prolonged in the inosine group. Inosine combined with PD-1/PD-L1 inhibitors has a synergistic effect that will provide a new option for overcoming immunotherapy resistance….In this trial, the median PFS in the inosine group was 2.6 months longer than that...

Zinc joins sodium and magnesium in driving immunotherapy response

Clinical data shows strong links to immunotherapy responses
Progression risks are halved in those with relatively higher zinc
Zinc drive immune system activity is proposed to support therapy

Our study provides preliminary evidence that there is a correlation between serum zinc levels and the efficacy of immunotherapy. This correlation is reflected in treatment response and overall survival in patients with advanced cancer. These findings not only underscore the importance of zinc in immune regulation and cancer therapy but also pave the way for developing predictive biomarkers and synergistic treatment strategies to enhance immunotherapy outcomes…These studies collectively suggest that zinc supplementation could serve as a therapeutic strategy for allergic diseases and as...

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Pathfinder Element	Risk Reduction Factor	Anti-Metastatic	Reduces Side Effects	Research Study
Astragalus	>50%	Yes	Yes	Link
Akkermansia/ Gut Health	>50%	Yes	Yes	Link
Danshen	>50%	Yes	Yes	Link
Antihistamines	>50%	Probably	Probably	Link
Selenium	>50%	Probably	Maybe	Link
Inosine with immunotherapy	>50%	Maybe	Probably	Link
Sodium with immunotherapy	>50%			Link
Zinc with immunotherapy	>50%		Maybe	Link
Ketogenic diet & supplements	>50%		Probably	Link
Beta glucans	26 - 50%	Yes	Yes	Link
Turkey tail	26 - 50%	Yes	Yes	Link
Aspirin	26 - 50%	Yes	Maybe	Link
Vitamin D3	26 - 50%	Yes	Maybe	Link
Red yeast rice/ statin	26 - 50%	Probably	Maybe	Link
Melatonin	26 - 50%	Maybe	Yes	Link
Lactoferrin	Up to 25%	Probably	Yes	Link
Oat and egg functional foods	Indirect - High	Probably	Yes	Link
Citrus Pectin	Indirect - High	Probably	Probably	Link
Urolithin a	Indirect - Moderate	Probably	Maybe	Link
Curcumin	Indirect - Moderate	Maybe	Maybe	Link

Plan Item	Cancers	Background Details	Trial Doses Under Supervision	References
Antihistamines	Breast, TNBC, Prostate, Lung, Colorectal, Kidney, Liver, Gastric, Ovarian, Cervical, Pancreatic, Melanoma, Lymphoma, Esophageal, Bladder	Research indicates desloratadine for localized cancers or loratadine for metastatic. There are examples of ebastine or other alternatives in certain cases. Growing research evidence indicates improved oncology responses. Taken between meals. Low histamine before and during treatment is beneficial.	Active use in clinical trials is still in early phase, follow the dose recommendation for instance 5mg daily unless under medical supervision where higher 10mg doses are frequent
Aspirin	Breast, TNBC, Prostate, Lung, Colorectal, Kidney, Liver, Ovarian, Cervical, Endometrial, Pancreatic, Melanoma, Myeloma, Head and Neck, Bladder, Gallbladder, Non Melanoma Skin, Gastric	Use of low dose 75 or 81mg "baby" aspirin is reported to benefit many cancer types across an average study group, and even all cause mortality. There are some indications of specific "responders" for instance those with existing inflammatory conditions or certain gene expressions. With food.	In a colorectal cancer trial responders were tied to the expression of particular genes (PI3KA). Doses were 160mg	LINK
Astragalus	Breast, TNBC, Lung, Colorectal, Liver, Gastric, Cervical, Endometrial, Pancreatic, Prostate, Kidney, Ovarian, Glioblastoma, Non Hodgkin, Lymphoma, Leukemia, Myeloma, Head and Neck, Bladder, Gallbladder, Thyroid	A typical astraglaus membranaceus supplement may have 50mg of astragaloside IV the main active compound. Its possible with meals can reduce any stomach upset. Use of a standard dose to help immune system balance before treatment.	Here, Astragalus is added to standard oncology in lung cancer Doses are 2-3 tablets of 250mg AMe (Solgar, NJ, USA) minimum for 6 months in this example	LINK
Beta Glucans	TNBC, Lung, Liver, Gastric, Cervical, Pancreatic, Melanoma, Non Hodgkin, Lymphoma, Leukemia	There are many options for mushroom or yeast 1,3/1,6 glucan and branded products include California Gold Immune Defense/Wellmune, AHCC, Biogen/ Yestimun, ImmiFlex, IP6 and many more. A pharma grade product, odetiglucan, is continuing in trials. Take on an empty stomach. Use a standard dose to help balance the immune system before starting treatments.	AHCC is used at 3x1g per day over several months during treatment. Beta glucans are used at 1-2g per day and higher.	LINK
Danshen	Breast, Prostate, Lung, Colorectal, Liver, Leukemia, Myeloma, Bladder	The most common chinese herbal medicine in oncology, also known as red sage. Premium brands such as MCS may recommend 1g twice daily as an ongoing dose. Its possible with meals can reduce any stomach upset. Start a standard dose a couple of weeks before treatment to help balance the immune system.	3 x1g daily between meals , over at least 90 days ideally longer to get maximum benefits according to reported patient outcomes, though even shorter dose period reduced risk	LINK
Green Coffee Extract	Glioblastoma	Supplements vary in terms of their chlorogenic acid content, it can be up to 50%. Quality brand might specify this level under their recommended intake. High dose commercial brands may be over 1000mg total, take before meals.	Analysis across trials reports metabolic health benefits start are higher at >500mg or daily. High chlorogenic acid content supplements eg Svetol have been trialed safely for 12 weeks at 200mg x 5 daily dose. As always, be aware of possible drug interactions	LINK
Red Yeast Rice Or statin	Breast, TNBC, Prostate, Lung, Colorectal, Kidney, Liver, Gastric, Ovarian, Cervical, Endometrial, Melanoma, Leukemia, Myeloma, Head and Neck, Esophageal	Red yeast rice is equivalent to lovastatin. Doses are essentially on the products, and there are many premium brands with guaranteed level of monokolin k around 3mg. A common theme is findings is those with improved cholesterol are "responders". With meals. Start cholesterol and inflammation reducing statins early.	Trial data is often case studies with multiple statins where lovastatin has average effects. Often atorvastatin and sometimes simvastatin come out on top. Research ususally reports intermediate doses ( 10-20mg) are effective but there are examples indicating higher doses under supervision.	LINK
Turkey Tail	Lung, Colorectal, Kidney, Liver, Gastric	A typical premium supplement such as MCS recommend 700mg twice daily with food. Mushroom based glucans can help balance immune response so start them before your treatment.	Pharma grade turkey tail, e.g PSP/ PSK/ Krestin is typically used at 3x 1g daily during oncology, up to 36 months and more. Trials in breast cancer have also used 3,6 and 9g daily regimes in 6 week periods	LINK
Vitamin D3	Breast, TNBC, Prostate, Lung, Colorectal, Gastric, Ovarian, Pancreatic, Glioblastoma, Melanoma, Non Hodgkin, Lymphoma, Leukemia, Myeloma, Head and Neck, Esophageal, Bladder	High dose commercial formulae can be 10,000IU. Which might be achieved by as little as 10 to 20 minutes in sunshine. Vitamin K2 is advised with D3. Take with some food containing fat. Its important to ramp these up before oncology treatments, and sustain the higher levels over time. Add magnesium for best absorption and metabolism.	The VITAL trial used 2000IU and discussed the potential of higher doses to increase responders especially higher BMI/ body weight. Whilst in prostate cancer there are trials demonstrating at least 10,000IU is required to see activity reducing PSA levels	LINK
Melatonin	Breast, TNBC, Prostate, Lung, Kidney, Liver, Ovarian, Cervical, Endometrial, Pancreatic, Glioblastoma	Commonly used in 10 to 40mg daily range no reported side effects, typically an hour before sleep.	Moderate and high dose trials report no significant side effects even at 1000mg daily	LINK
Citrus Pectin	Breast, TNBC, Prostate, Lung, Colorectal, Kidney, Liver, Ovarian, Cervical, Endometrial, Pancreatic, Non Hodgkin, Leukemia, Myeloma, Head and Neck, Esophageal, Bladder, Gallbladder, Thyroid, Gastric	Trials use a recommended dose up to 5g x3 daily and no significant side effects. Taken 30 minutes before or 90 minutes after food. Ideally, start PectaClear or similar products at least 4 week before treatment to reduce heavy metals. But sustain zinc with supplementation	Even in children age 5 to 12 the daily regime 3 x 5g was safe and effective for heavy metal chelation	LINK
Soy Isoflavones	Breast, Prostate, TNBC	Often dietary sources, tofu and soy based and no evidence of side effects. Supplements generally with food.	In a clinical trial setting up to 900mg with no issues	LINK
Fermented Wheatgerm	Prostate, Colorectal, Melanoma	Trials are with Avemar brand products with no significant safety concerns reported	Typical dose regimes may be aroung 9g daily over longer time periods for instance 12 months	LINK
Iodine	Breast, TNBC	General usage around 1000mcg or 1mg generally with food	Successful pilot studies in breast cancer use 5mg molecular Iodine daily for the duration of therapy	LINK
Lactoferrin	Breast, TNBC, Prostate, Lung, Colorectal, Kidney, Liver, Gastric, Ovarian, Cervical, Endometrial, Pancreatic, Glioblastoma, Melanoma, Non Hodgkin, Lymphoma, Leukemia, Myeloma, Head and Neck, Bladder, Esophageal, Gallbladder, Thyroid	200mg typical use daily , eg 10ml liposomal formula ideally 30 minutes before meals or 2 hours after. No side effects of note. Start this immediately to achieve and maintain healthy iron absorption, avoid deficiencies and reduce cancer related ferritin levels.	During oncology doses of up to 3g to 9g daily, even higher, have been used with significant side effects	LINK
Selenium	Breast, Lung, Kidney, Ovarian, Cervical, Endometrial, Pancreatic, Melanoma, Head and Neck	Supplements are 200ug doses and similar amounts from about 3 brazil nuts. Start buildin gup your levels immediately and keep them high during oncology. Selenium toxicity is a consideration for high doses over time, so seek medical advice. Ideally taken with meals.	This trial used 2500 to 4000ug 2x daily for 14 days then once daily in kidney cancer with no dose limiting toxicity	LINK
Vitamin B3	Liver, Gastric, Glioblastoma, Non Hodgkin, Lymphoma, Leukemia, Non Melanoma Skin	Typically 500mg for nicotinamide (niacinamide) form of B3 taken ideally with meals	Do not differ from standard doses, here 500mg twice daily related to skin cancer	LINK
Akkermansia	Breast, TNBC, Prostate, Lung, Kidney, Liver, Ovarian, Cervical, Pancreatic, Non Hodgkin, Lymphoma, Leukemia, Myeloma, Head and Neck, Gastric	Commercial products may be at 10B CFU typically 30 minutes before or 2 hours after food. Ramp up levels with diet and moderate supplementation before treatments, especially immunotherapy.	Under development. Results in oncology indicate this is one of many helpful guy bacteria. careful consideration and particularly following use of antibiotics. Diversity is crucial.	LINK
Berberine	Kidney, Liver, Cervical, Pancreatic, Non Hodgkin, Leukemia, Myeloma, Head and Neck, Esophageal, Gallbladder, Thyroid, Non Melanoma Skin, Melanoma, Bladder	A natural anti-diabetic used frequently at 400mg daily and above, shortly before meals	In metabolic health trials frequentlu use up to 500mg at 3 times daily .	LINK
Curcumin	Colorectal, Liver, Non Hodgkin, Myeloma, Bladder, Gallbladder, Non Melanoma Skin, TNBC, Breast, Prostate, Lung, Kidney, Gastric, Ovarian, Cervical, Endometrial, Glioblastoma, Melanoma, Lymphoma, Leukemia, Head and Neck, Thyroid	Doses from 500mg to 2000mg frequently seen. Piperine fron black pepper improves absorption, highly bioavailable formulae are available. Ideally with a meal containing fat.	Higher doses in trials are frequently 2 of 4 g daily (+40 mg piperine) during oncology for instance here at 3 periods of 30 days	LINK
Quercetin	Glioblastoma, Myeloma	Can be found in a healty diet. Supplements often 500 or 1000mg and can be taken with tocotrienols for enhanced absorption, a form of vitamin E . Some evidence that Quercetin should be pulsed on/off.	Clincial trials have safely used up to 5g daily in adults, and 1 to 4g for rare forms of paediatric anemia	LINK
Urolithin A	Prostate, Lung, Colorectal, Kidney, Gastric, Glioblastoma, Melanoma, Myeloma, Gallbladder, Head and Neck	Typical commercial brands run at 500mg once or twice daily, with or without food, some brands suggest with meals	Trials eg in anti-aging science use the same dose range	LINK
Oat and Egg Functional Food	Breast, TNBC, Prostate, Lung, Colorectal, Kidney, Liver, Cervical, Pancreatic, Glioblastoma, Melanoma, Head and Neck, Gallbladder	Follow supplier guidance on dosage and use. https://shop.lantmannenfunctionalfoods.com/? Lowering tumor fluid pressure helps treatments work, start these before your treatment if possible. Use egg based salovum for short term "pulse" during therapy and oat products for sustained use over longer time periods	This trial in glioblastoma used 16g egg based Salovum four times daily. It discusses lowering that regime in follow on trials.	LINK
Coffee	Breast, Prostate, Colorectal, Liver, Non Melanoma Skin	Most dietary studies use standard 8oz servings as a guide. In many cases the findings are that benfits increase with intake. But in some cases such as prostate cancer there are important details in the PATHFINDER	No, but chlorogenic acid and, separately, green coffee extracts are used at 400mg and up to 2000mg
Flax	TNBC, Ovarian	Crushed flaxseed alone or in foods around 1/4 cup daily	Doses up to 50g daily in clinical trials for various diseases. Here a fairly typical 30g regime in inflammatory liver diseases	LINK
Propolis	Breast	Typical supplements range from 400 to 1000mg	Here 400mg x3 daily help recovery from radiotherapy	LINK
Walnuts	Prostate, Colorectal, Melanoma, Head and Neck	Dietary food item shown even at low useage to be helpful even at a few oz per week	Here, 2oz (56g) daily showed measurable activity in breast cancer	LINK
Mushroom	Prostate	Both dietary sources and many commercial supplements normally taken with food	In this example some patients saw responses between 8 and 14g daily of button mushroom extract	LINK
Zinc	Kidney, Ovarian, Cervical, Endometrial, Head and Neck, Non Melanoma Skin	Commercial supplements vary considerably . Moderate 20mg range generally advised	No
Intravenous HIgh Dose Vitamin C	Pancreatic, Glioblastoma	Commercial supplements vary. A moderate range around 20mg with food is generally accepted as safe.	Same as general guidance
Alpha Ketoglutarate	Melanoma, Kidney, TNBC, Non Hodgkin, Lymphoma	Typical usage is 1000mg daily with or without food, safety is good. Its especially important to ramp up and sustain your levels for maximum immunotherapy responses.	Larger doses of several grams have been safely used in various trials including here in bone disease at 6g daily	LINK
Horse Chestnut (Escin)	Thyroid	Common 300 to 600mg supplements contain 50 to 120mg of active compound, escin taken with food	Escin up to 150mg daily in vascular health. In oncology 0.6 mg/kg/day for 9 days, intravenous injection has been used, high absorption premium supplement would reacj this level	LINK

Impact	What	Why	Dose	Impact summary	Additional stage treatment incl chemo	Activity against bone metastatic sites	Anti-metastatic in general	Higher doses eg in clinical trials	Other comments or sources
>50% for good hemoglobin	Lactoferrin	Large benefit to well balanced iron levels and higher hemoglobin	10ml lipsomal LF daily, ideally on empty stomach	Good hemoglobin is essential for strong treatment response. And in case studies, 25% of patients get results even with chemo	Benefits also with chemo, chemo plus immunotherapy with good hemglobin by far the longest responses	Balanced iron metabolism is reported to reduce bone related inflammation and metastatic spread	Low iron levels strongly linked to increased metastatic activity	Only with chemo. 1.5g lactoferrin twice daily 1.5 g for three 6-week cycles used in lung cancer	Hemoglobin over 110g/dL is reported with 2X effect vs lower. 130 to 150g/dL would be good. Low ferritin levels reduce progression risk from 60% to over 2X
>50%	Sodium during immunotherapy	Boosts and activates immune response, enables strong anti tumor activity	With diet around 6g-8g daily, need to be at 140-145mmol/l	Recently seen as crucial to immunotherapy response, linked with almost all long term responses	Astonishing 9X higher response rate with enough sodium (kidney cancer)	Indirectly, well balanced levels are a benefit	Surprisingly, LOW sodium has growing evidence of increasing metastatic activity	This is not defined but up to 2/3 of patients during immunotherapy see low salt levels	High risk that immunotherapy causes deficiency after 4-6 weeks. Consider increasing dietary intake
>50% with immunotherapy, good with any therapy	Red yeast rice or statin	Anti-lipid and anti-inflammation, consistent evidence	Per the supplier guidance. Use a premium brand	Multiple studies from patient records. Effects mainly for post-dagnostic use especially LDL "responders"	Statins improve immunotherapy results across most cancers, typically by 2X	Yes, direct evidence reports benefits extend to bone health and repair	Probably	There is evidence risk reductions up to 60% or so with higher doses under supervision	Useful to know if LDL dropped with statin use. Interesting synergies with nattokinase (Supplement Library)
>50% for immunotherapy, 25-50% chemo	Vitamin D3	Boosts and activates immune response, enables strong anti tumor activity	At least 10,000IU daily with meals	For all treatments the link to higher D3 is clear and in immunotherapy data in other cancers shows around 2X	Across many other cancer types higher D3 levels are reported to improve results yes	Higher levels are essential for healthy bone metabolism. Chemo depletes D3 so this is crucial	Yes	Research is into higher doses in order to increase the proportion of "responders"	Existing trials assessed 30ng/ml as sufficient. Other studies actively discuss supplementation to reach at least. 40ng/ml. Be sure to include magnesium and K2
>50%, lower with chemo	Zinc especially during immunotherapy	Essential for supporting immune response	Use high absorption formula 20 to 40mg	Newly reported as doubling response in other cancers, its likely to transfer to TNBC too	Maintaining Zinc is always important including with chemo	Perhaps	Maybe	Unclear but moderation is probably good	About twice the response rates with good zinc levels in other cancers
>50% with ICI, indirect-high overall	Alpha Ketoglutarate (Ca-AKG) during immunotherapy	Helps immunotherapy drugs overcome evasion	500mg x2 daily any time	Patients with high AKG levels have around 2X response rates	Evidence so for for PD-1 blockade for instance nivolumab and pembrolizumab	AKG has related evidence in anti aging science and is gaining in attention in researchers work	likely yes, there is lab evidence for this	YES Load up Ca-AKG before and during therapy	AKG may be lowered by metformin. This anti aging supplement has excellent safety
>50% with ICI, indirect-high overall	Gut health including akkermansia	Indirect importance of gut bacteria is crucial in immunotherapy	Supplier dose, moderate level	Crucially, metastatic spread to the bone is linked to lack of a diverse microbiota including low akkermansia.	Has become a recognized factor in immunotherapy success, with likely strong importance here too	Poor microbiome is indeed linked to progression of inflammatory responses in bone	Yes	No, evidence is to apply moderation with supplements and lead with diet	Foundation here is high vegetable and high fiber diet
>50%	Inosine especially with immunotherapy	Immune cell activation increases	500 to 1500mg	Specific to immunotherapy, large benefit but being explored with chemo	May help reverse resistance to chemo, there is an ongoing trial	Pre-clinical evidence shows potential activity in bone health mechanisms	Maybe. A trial ongoing in breast cancer	Not to date	Trial with chemo at 200mg x 3 per day in breast cancer. But this has high safety
>50%	Astragalus	Natural immune system vitality and balance	At least 500mg daily (50mg astragalaside)	Substantial especially with TKI erlotinib or chemotherapy, side effects too	No evidence so far in immunotherapy, indirect evidence via NLR re-balancing	No research on this	Yes	Prescribed doses of 3g per day are typical in first months	Based on evidence in lung cancer, an excellent natural immune modulator in the absence of immunotherapy
>50%	Danshen	Improves blood circulation, immune system balance and activity level, can often reduce side effects. Studies focus on chemotherapy	At least 500mg daily	Large scale evidence for risk reductions of a half. Especially postmenopausal patients	Danshen evidence is focused in chemo, like astragalus its evidence is growing	Pending studies, narrative reports do indeed highlight danshens probable benefit	Yes	Prescribed doses of 3g per day are typical in first months	Reduces many usual drug side effects during treatment and has protective effects in vascular health
>50%	Desloratadine	Help immune system function and side effects	1 or 2 x 5mg daily	Large scale analysis of patient records reports this effect	Yes including lung cancer and more	Yes, histamine is a recognised driver of bone inflammatory responses via so called Mast cells	Probably	No current evidence but generally safe	Loratadine is reported as effective in metastatic disease stage . see Supplements Library
>50%	Keto genic diet & supplements				No evidence to date	No evidence to rely on here
26-50%	Beta Glucans	Balance and help regenerate immune system, and reduce side effects	1 or 2x 250mg California Gold Immune Defense with Wellmune	Yes from some patient case studies	Yes beta glucans have some evidence in liver cancer progression	No evidence	Yes there is research showing effects in lung cancer	As with astragalus
26-50%	Turkey tail, may alternate with beta glucans	Balance and help regenerate immune system, and reduce side effects	700mg twice daily	Consistent evidence across multiple clinical trials	Not directly but many reports in digestive system cancers	No evidence	Yes there is research showing effects in lung cancer
26-50%	Melatonin	Boosts natural immune system activity	Often 10 to 20mg evenings	Higher doses are reported with striking effect in late stages. More is needed on continuous use.	Yes the benefits have included liver cancer	No evidence	Yes there is positive evidence for melatonin	100mg and even 1g have shown responses in late stage trials	Reported to improve problems of restricted breathing in advanced stage LC
Up to 25%	Propolis ( with radiotherapy)	Protective actions against radiation induced cell damage	Per supplier	The data available shows very beneficial support for radiotherapy	Focused on radiotherapy	No evidence	No current evidence	Trials have used 400mg x3 daily doses
Indirect - high	Citrus Pectin / Pectaclear	Reduce copper and harmful metals, also help sugar metabolism and microbiome	Copper removal with Pectaclear at 2g x 2 daily on an empty stomach	Heavy metals strongly linked to poor prognosis. Possible anti-metastatic activity too.	Indirect evidence	Cadmium and to a lesser degree copper are linked to dysfunctional bone metabolism	Indirect evidence due actions on so called Gal-3 known metabolic activity in sugars	Follow supplier program	Exposure to tobacco may contribute to heavy metal build up. Cleansing is essential if you are at risk
Indirect - moderate	Anti-inflammatory diet	Lowering inflammation is crucial	Continuous	Research evidence continues to grow for mainly vegetarian diet with higher fiber content	Always a valid approach	Maybe/ probably	Yes	Combine wtih supplements	Also read Lifestyle section for view on evidence in diets and eating patterns
Indirect - High	Oat and Egg functional foods (especially with chemotherapy)	Helps treatment side effects and potentially weakens physical tumor resistance	Per supplier	Clinical trial ongoing primarily to reduce side effects. Especially chemo related and reducing metastatic activity	No current evidence	Pending clinical trial results, this seem likley yes	Similar , indirect evidence so far	No data	Ongoing phase III trial looking at reducing treatment side effects especially gastrointestinal....may reduce tumor resistance
Indirect - Moderate	Urolithin-A	Under investigation for lipid metabolism management	500 or 1000mg	Ongoing trials, see Pathfinder Analyis	No current evidence		Maybe	Not researched
Indirect - Moderate	Curcumin	Good supplement in anti-inflammatory diet	Per supplier. Get a high absorption formula	Has potential copper removal actions and more	Some evidence of direct activity combined with taurine		Maybe	Follow supplier program	Combine with piperine or black pepper
Other	AM Immunotherapy	Unclear why results are better before 4pm		Around 40% risk reduction shown for other cancers
	Magnesium	early reports of 2X improved response to immunotherapy	Use high absorption formula	Ongoing research with preliminary confirmation of key benefits to immunotherapy

Immunotherapy treatments such as pembrolizumab (Keytruda) and nivolumab (Opdivo) are frequently first line when there is no clear driving genetic factor, including with chemotherapy especially for patients less likely to respond to immunotherapy. For EFGR or ALK driven type cancers its common with tyrosine kinase inhibitors such as osimertinib (Tagrisso) and erlotinib. These often play a role in second line treatments too.

To give some perspective on risk reductions from adding drugs to a base line treatment, consider the data for adding chemo to immunotherapy. As seen in the Examples on the Home page, a 2024 study comparing overall results of adding chemo to pembrolizumab (keytruda), the worlds largest selling oncology drug . For around three quarters of patients in the group with PDL-1 expression under 50%, the report shows risk reduction of 23% is achieved by adding chemo https://pmc.ncbi.nlm.nih.gov/articles/PMC11273333/ and for the “responders” with higher PDL-1 there is no benefit from adding chemotherapy, only its side effects

Lung cancers are the largest group in this real world study of over 1700 patient cases with immunotherapy. Another illustration is adding ipilimumab (Yervoy) to nivolumab (Opdivo) produced similar or worse outcomes and much higher side effects https://jamanetwork.com/journals/jamaoncology/fullarticle/2809043 Though data in other cancers has shown stronger benefits in low risk patient groups.

Your PATHFINDER brings together research that may help maximize the effects of chemotherapy, immunotherapy or targeted drug treatments. The IMPACTS tab summarizes these and can lead to Many more Good days by helping these treatments work, reducing your risk for progression and by easing treatment side effects. If you do elect both chemotherapy and immunotherapy or targeted drugs, you can continue to look for ways to increase the results and reduce possible toxicities;

Be sure to fully read and absorb the PATHFINDER and its Impacts summary
If you have metastatic sites take a look into the corresponding Pathfinder for those too, for inspiration.
Use the Supplement Library Index and filter on “Chemotherapy” and “Immunotherapy” for ideas.
The Foods Library can complement your plan, including anti-metastatic strategies and metabolic health
In the Lifestyle section gathers fascinating evidence for diets and exercise
The PLANS section may have information from what others are doing and have learned

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