Liver

Comparing patients during sorafenib therapy (Nexavar, a so called tyrosine kinase inhibitor) has shown much lower side effects in those who took antihistamines. Treatment withdrawal rates due to effects of the oncology drugs were halved, resulting in longer treatment duration. This contributes to much higher response rate and progression free time, on average. In a similar way, patients also taking low dose aspirin, usually around 80mg, are also seen in research studies to have better results for both progression and all cause risks. Including use with sorafenib as first or second treatment, as well as following thermal ablation surgery. And improving all cause risks in another study of patient data during hospitalization. Aspirin even helped protect against the damaging impact of anti-diabetic drug metformin (see Repurposed Drugs)

Those taking statins following surgery, inlcuding transplants,have up to 70% lower risk of cancer recurrence accorind to studies of case data. This has even been confirmed by analysis across multiple research publications. Atorvastatin is the most researched, but when a prescription is lacking, red yeast rice is the readily available supplement source of lovastatin. Another fascinating example is coffee consumption. Beyond its well established risk reduction for liver cancer incidence, there is a remarkable lack of research on its lowering of progression risks. But recurrence rates following liver transplants shows a large benefit for consuming 3 or more standard 8oz cups daily, and commentary in research is increasingly positive on coffee consumption for liver health including cancer.

Consistent positive results come from trials of mushroom extracts containing so called beta glucans, adding these alongside oncology regimes. Examples include lentinan which is from shiitake mushroom, and for remarkably well proven turkey tail. Similarly, well proven and widely available danshen and astragalus, the two most well researched herbal extracts, have large scale analysis across several trials finding both reduced risks and fewer serious side effects. The impact of these supplements is through their ability to protect and balance the immune system.

Study of genetic data and outcomes shows immune system evasion by liver cancer cells involves some specific increases in certain gene activity levels. These can be regulated by vitamin B3, and some compelling pre-clinical research shows this with patient derived liver tumor samples. Along the same line, higher levels of lactoferrin, a prebiotic compound, are reported with slow disease progression rates and lab work on this supports this both as a standalone supplement and with the TKI, sorafenib.

Dysfunctional iron metabolism is common during cancer and with treatments. Liver cancer can utilize extra iron it stores locally to fuel growth, seen in the enzyme like protein marker called ferritin. Lower ferritin levels are clearly linked to improved outcomes in cancer. Conversely iron deficiency is itself reported with poor prognosis. Lactoferrin is a pre-biotic class milk protein which helps restore iron balance, so called homeostatis improving both absorption can healthy use of iron. Also related to metals, incidence and much more aggressive progression rates are linked with high levels of circulating copper. Citrus Pectin can help remove these heavy metals, especially with alginates from brown seaweed. And, has its own anti-cancer evidence both in late stage patient trials and its reported ability to reduce so called galectin-3 protein signaling, shown to increase patient risk.

Many solid tumors, not least liver, have an internal fluid pressure that acts both to push metastatic spread, literally, as well as making it hard for oncology drugs to penetrate. There are ongoling trials in several cancers including colon with funtional oat and egg compounds that both reduce this pressure and can reduce side effects. Selenium is also being researched in this area in kidney cancer. Another well known behavior with much the same results is so called hypoxia, and in liver cancer there is compelling lab work pointing to melatonin use to help reduce this, as well as improving quality of life.

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 can probably make a significant difference. Commonly used astragalus root is reported to improve immune system balance (lower NLR) while curcumin and other other functional foods including garlic can help bring down “classic” inflammation (and CRP), as can lactoferrins actions. Trials supplementing probiotic b.longum have been beneficial in patients, whilst another gut bacteria akkermansia is suggested to increase immunotherapy responses. Also in metabolism, upregulated amino acid tryptophan is shown to drive progression. A variety of supplement and functional foods have been shown in studies from other fields to reduce these levels.

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). For immunotherapy the presence of high sodium levels is now identfied as a key marker for success in other cancers. Also in other cancers, AM treatment programs are substantially more effective that PM/evening sessions. And, there are some remarkable results for improving immunotherapy responses using structured exercise regimes (see Lifestyle)

The most common metastatic site is lung, take a look at that for ideas there too. And if receiving immunotherapy, note that research reports better reponses for morning sessions. Also, recent studies in sodium levels link response rates to higher natural levels of circulating sodium during treatment.

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Antihistamines have large scale analysis of case data supporting their use in most cancers

A large 76% lower progression risk when added to TKI (eg Nexavar) therapy
Similar 80% increase in average progression free period with antihistamines
Side effects reduced, enabling 50% longer oncology treatment and better responses

Our results indicate that cyproheptadine in combination with sorafenib prolonged the OS and PFS of sorafenib-treated advanced HCC cases. The percentage of patients with partial response or stable disease in the combination group was almost twice that in the control group. In contrast, the probability of sorafenib dose reduction was reduced by approximately half in the combination group compared with the sorafenib control group. The sorafenib–cyproheptadine combination may provide a prospective future for advanced HCC. However, this study was only a retrospective study. A prospective clini...

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

Risk reductions of 43% with sorafenib, more than 2X as an absolute impact
In relapsed patients, with regorafenib even larger 80% reduced risk is reported
Possible link to specific genes , the PI3K pathway dysfunction as seen in colorectal cancer,

Our results highlight that aspirin may play a role not only in preventing hepatocarcinogenesis but also in increasing the outcome of advanced HCC patients receiving sorafenib…Biological reasons behind these results are unknown, but aspirin appears to be able to inhibit the expression of COX-1 at the platelet level …Platelets facilitate immune-mediated liver injury by promoting the hepatic accumulation of virus-specific CD8 (+) T cells and the use of aspirin reduce this damage. These mechanisms reduce the level of growth factors involved in the epithelial–mesenchymal transition...

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

Analysis of patient data shows large reductions in post surgery recurrence rate, including transplants
Approximately 70% risk reduction, including only 13% recurrence rate at 3 years when taking statins
Red yeast rice is the natural source of lovastatin where prescription statins are not available

Statins increase the disease-free survival of patients with HCC after liver surgery. These drugs seem to have chemoprevention effects that decrease the probability of HCC recurrence after liver transplantation or liver resection…We showed that the recurrence was lower at one, three, and 5 years after surgery in patients with HCC who underwent liver surgery in combination with statin treatment than in patients who underwent liver surgery without statin treatment. These results indicate that statins should be considered effective at reducing the recurrence of HCC tumors..Statins may red...

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

Risk reduction of more than half shown by adding well proven danshen supplements
Analysis across multiple trials finds evidence of even higher impacts in some studies
Along with astragalus, the most well proven and available herbal supplements

The current meta-analysis found that Danshen formulae can improve the clinical efficiency in cancer treatment. After the addition of Danshen formulae, RR and survival rates were significantly improved. …The studies investigated [including] liver cancer (n = 3)…Meta-analysis [compared to chemotherapy only] suggested that Danshen formulae had a significant effect on RR (response rate) (OR 2.38, 1-year survival (OR 1.70) [meaning +70%], 3-year survival (OR 2.78) [nearly 3X], and 5-year survival (OR 8.45)…The current research results showed that Danshen formulae combined with ...

Coffee show surprising risk reducing effects from dietary survey data in many cancers

Data in report shows no recurrence at 3x 8oz cups or more daily vs average 18%
Overall, drinking coffee is reported to reduce recurrence rates around 70%
An overall summary here is half the relative risk levels in those consuming coffee vs none

Coffee consumption is associated with a decreased risk of HCC recurrence and provides for increased survival following OLT. We suggest that these results might be, at least in part, associated with the antagonist activity of caffeine on adenosine-A2AR mediated growth-promoting effects on HCC cells….Ninety patients underwent OLT [liver transplant] for HCC. Sixteen (17.8%) patients experienced HCC recurrence after median time of 11.5 months (range 1‐40.5). For overall survival postoperative coffee intake emerged as a major factor of hazard reduction in a multivariate analysis (HR = 0....

Curcumin has some direct evidence here for HCC, and helps reduce systemic inflammation

Pilot study in liver cancer shows a large impacts, less than half the risk of progression
The 3 supplement combination here are shown to strongly suppress crucial markers of poor prognosis
These markers are crucial in advanced stages and after surgery in HCC, including transplants

The combined treatment was able to produce a significant decrease in the levels of serum IL-10, and miR-21 while it resulted in a non-significant up-regulation of serum miR-141 expression level. At the end of the follow-up period, the median overall survival (OS) rate was found to be 17.00 months with a worse OS in patients with high baseline levels of circulating IL-10 and miR-21 compared to those with low levels. In contrast, a low baseline level of circulating miR-141 was associated with poor prognosis

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

Analysis across several trials shows over 40% reduced progression risks
At 12 months, a relative risk reduction level of 28% and improvement in many side effects
Evidence of balancing immune related inflammatory response aligns with this study

Our meta-analysis displays compelling evidence of effectiveness for hepatocellular cancers that should be evaluated in high-quality and transparent clinical trials…Products containing ginseng, astragalus and mylabris had a larger treatment effect (OR 1.34) than the pooled broad estimate, also the case for astragalus-based treatments (OR 1.35). We examined survival rates and pooled 15 studies reporting on 6 month outcomes (RR 1.10). This effect was consistent at other prospective dates, including 12 months…

Turkey tail extracts have extensive evidence in digestive system cancers

Similar benefits to digestive tract cancer studies found here
The most clear impacts are reported in slowing advanced stage progression
Lowered side effects and better quality of life also confirmed here

Median PFS was 2.5 (1.4-5.3) months in the CV and 1.1 (0.4-4.2) months in the placebo arm, HR 0.42 (0.13-1.34, p = 0.144). Median OS was 6.5 (3.3-24.1) and 2.2 (0.8-23.3) months, respectively, HR 0.35 (0.10-1.25, p = 0.105). Social and emotional functioning scores were higher in the CV group compared to placebo group on treatment. CV subjects had less appetite loss and pain symptoms compared to placebo subjects during treatment.

Beta glucans protect and balance immune system activity improving outcomes

A functional food high in mushroom beta glucans reduces progression risks by 30%
Commercially available products contain refined lentinan from shitakke
Some patients are “responders” to the mushroom beta glucan and see larger impact

Survival times of patients who ingested test food for a mean period of 47 weeks (range, 26 to 145 weeks) were significantly longer than that of patients who ingested for 7 to 12 weeks (p < 0.05). The rates of lentinan-binding cells in CD14+ monocytes showed individual variations (0.1-19.7%; Median, 1.6%). Survival times (median survival time, 16.3 months) of lentinan-high-binding group were significantly longer than those (median survival time, 12.5 months) of lentinan-low-binding group (p < 0.05).

Nicotinamide version of B3 research in the Supplements Library

Patient data analysis associates poor progression with GPR109A immune cells used by HCC
Pre-clinical mouse models show surprisingly large suppression of patient derived tumors
Study suggests high probability of vitamin B3 increasing both immunotherapy and targeted TKI results

In summary, our research uncovers the immune-modulatory activity of VB3 in the TME. Dietary supplementation of VB3 enhances the antitumor responses of adaptive immunity by counteracting immunosuppressive myeloid cells and improves the efficacy of immune/targeted therapy. These findings establish a mechanistic link between dietary vitamins supplementation and cancer progression, suggesting that VB3 could be readily translated into clinical use as an adjunctive treatment for liver cancer.

Lactoferrin increases iron balance and reduces anemia rates, countering cancers use of iron

Study finds high levels in tumor environment lead to better outlook
Pre-clinical testing confirms lactoferrin alone has anti-cancer mechanisms
Study suggests strong synergies with sorafenib based on lab testing

We found endogenous hLf is downregulated in HCC tumors compared with normal liver, and decreased hLf levels in HCC tumors are associated with shorter survival of HCC patients. However, the chemoprotective effect of 100% iron saturated holo-bLf on experimental hepatocarcinogenesis has not yet been determined. We aimed to evaluate the chemopreventive effects of holo-bLf in different HCC models. Remarkably, a single dose (200 mg kg−1) of holo-bLf was effective in preventing early carcinogenic events in a diethylnitrosamine induced HCC in vivo model

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

Analysis of patient data for key markers elevated with recurrence and treatment evasion
Detailed pre-clinical studies showing substantially improved immunotherapy results
Melatonin alone shows suppression of tumors in the lab by regulating the tumor micro-environment

In conclusion, the present findings establish a clear role for melatonin in improving the hypoxic immunosuppressive microenvironment of tumors, reducing tumor progression, and enhancing the efficacy of anti-PD-L1 antibodies in treating residual tumors. Elucidating this potential mechanism further will provide a solid scientific basis for targeting the hypoxic microenvironment to prevent HCC recurrence and metastasis in clinical RFA practice.

Berberine improves metabolic heath in both glucose and lipids

Elevated levels of TIGAR sugar metabolism strongly affect prognosis
Liver cancer switches this pathway, introducing at least 54% higher relative risk
Berberine research shows it strongly binds TIGAR in its glucose clearing actions

Our findings shed light on the complex interplay between TIGAR expression and immune cell infiltration within the tumor microenvironment, providing valuable insights into the mechanisms underlying HCC development and progression..Our study revealed a compelling association between high TIGAR expression and diminished OS rates in HCC patients. Through GSEA, we have established a close relationship between TIGAR and humoral immunity, indicating the pivotal involvement of TIGAR in modulating the body’s antibody-mediated immune responses

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

Analysis of patient records and their relative levels of so called Galectin-3
The 7X risk reduction here is large, but new data in US shows 25%
Late stage trials showed some relapsed patients benefitting too

We divided them into two subgroups (high galectin-3 expression and low galectin-3 expression) and compared outcome between the two groups. The Kaplan–Meier survival analysis revealed that patients with high galectin-3 expression had a significantly shorter survival time than those with low galectin-3 expression. In the multivariate analysis, we observed that galectin-3 expression, together with some traditional prognostic factors (tumor size, histologic grade) were independent risk factors in the prognosis of HCC patients. Similar findings have been reported in other malignancies

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

These studies show internal fluid pressure in HCC tumors increases spread
Most solid tumors have an internal pressure that is a barrier to oncology drugs
Specific anti-inflammatory responses can be driven by use of functional foods

Elevated tumor pressure is strongly associated with increased metastatic potential and poor prognosis across various cancers. Consequently, tumor pressure has emerged as a promising biomarker for predicting malignant behavior and therapeutic response. Tumor cells adapt to this high-pressure environment, which promotes their proliferation and invasion. In liver cancer, PHT plays a significant role in creating HIFP within the tumor microenvironment. This condition is not only a common complication in liver cancer patients but also affects the onset and progressi...

Akkermansia and B.longum can be stimulated to natural levels with functional foods

A clinical trial improves post surgery recovery and outcomes
A 35% risk reduction in patients given Bifidobacterium longum
For immunotherapy, other studies highlight akkermansia as crucial

In a clinical trial of HCC patients, orally administering a probiotic bacteria cocktail containing B. longum reduced the rates of delayed recovery, shortened hospital stays, and improved overall 1-year survival. These benefits, attributed to diminished liver inflammation, reduced liver fibrosis, and hepatocyte proliferation, were associated with changes in key metabolic pathways, including 5-hydroxytryptamine, secondary bile acids, and short-chain fatty acids. Our findings propose that gut microbiota modulation can enhance LFR, thereby improving postoperative outcomes for HCC pati...

Garlic and its extracts reduce inflammation and improves blood vessels integrity

Low inflammation levels triple average survival rates
Time to treatment was doubled in lower vs higher CRP
Similar findings with immunotherapy treatment in other reports

It is noteworthy that a high-CRP level has been reported to be a poor prognostic factor in HCC patients treated with immune checkpoint inhibitors…this investigation revealed a significant association between baseline CRP levels and prognosis in patients with HCC undergoing lenvatinib treatment. Elevated CRP was identified as a substantial negative predictor of OS, even in patients with relatively healthier liver function. Importantly, a serum CRP level exceeding 0.5 mg/dL at baseline was determined to be an unfavorable prognostic factor in HCC patients treated with lenvatinib.

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Pathfinder Element	Risk Reduction Factor	Anti-Metastatic	Reduces Side Effects	Research Study
Aspirin	>50%	Yes	Maybe	Link
Antihistamines with Immunotherapy	>50%	Probably	Probably	Link
Red yeast rice/ statin	>50%	Probably	Maybe	Link
Danshen	>50%	Yes	Yes	Link
Lactoferrin	>50%	Probably	Yes	Link
Curcumin/ Taurine/Piperine	>50%	Maybe	Maybe	Link
Astragalus	26 - 50%	Yes	Yes	Link
Beta glucans	26 - 50%	Yes	Yes	Link
Turkey tail	26 - 50%	Yes	Yes	Link
Coffee	26 - 50%	Maybe		Link
Melatonin	Up to 25%	Maybe	Yes	Link
Exercise with immunotherapy	26 - 50%	Maybe	Probably	Link
Gut health including Akkermanisa	Indirect - High	Probably	Yes	Link
Oat and egg functional foods	Indirect - High	Probably	Yes	Link
Citrus Pectin	Indirect - High	Probably	Probably	Link
Berberine	Indirect - Moderate	Maybe	Maybe	Link
Garlic and black garlic	Indirect - Moderate	Probably	Maybe	Link
Vitamin B3	Indirect - Moderate	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 treatment - targeted drug	Activity against Lung metastatic sites	Anti-metastatic in general	Higher doses eg in clinical trials	Other comments or sources
>50%	Low dose Aspirin	Reduce blood clotting improves vascular health, specific reasons remain unclear	75mg	Reported 2.2X effect, possibly linked with PI3K gene. With TKIs	Yes the same 2X effects also evident in advanced stage treatments	Play a role reducing metastatic activity and has clear evidence for liver cancer tumors	Yes	Colorectal cancer trial used 160mg.	Metformin use is reported to be damaging for HCC progression. Low dose aspirin is protective against this
>50%	Desloratadine antihistamine	Help immune system function and side effects	1 or 2 x 5mg daily	There are reported impacts of 2-3X in absolute terms, with sorafenib (Nexavar)	Yes including lung cancer and more	Indirectly - an 80% and much lower side effects (loratadine) in lung cancer immunotherapy	Probably	No current evidence but generally safe	Loratadine is reported as effective in metastatic disease stage . see Supplements Library
>50%	Red yeast rice or statin	Anti-lipid and anti-inflammation. Effects maybe linked to lowering LDL	Per the supplier guidance. Use a premium brand	Large scale analysis of patient records confirms this. And large reduction in post surgery recurrence	Effects are continuous across treatments, and in preventing new tumors after surgery or transplant	Large scale data shows slower progression in liver cancer yes	Probably	Assessments are inconclusive	Atorvastatin or similar prescription drug is likely a good option if available. Red yeast rice can potentially be combined with nattokinase
>50%	Lactoferrin	Large benefit to well balanced iron and hemoglobin through treatment	10ml lipsomal LF daily, ideally on empty stomach	The benefit of well functioning iron metabolism is very large, more than 2X effect in HCC	Evidence shows essential need for well balanced iron levels with all drug treatments	Indirectly since poor hemoglobin is strongly linked to faster progression in lung cancer	Low iron levels strongly linked to increased metastatic activity	1.5g lactoferrin twice daily 1.5 g for three 6-week cycles used in lung cancer	Reported impacts at least 2x for sustaining hemoglobin >90g/l through treatment, which otherwise depletes iron badly (especially chemo). See Supplement Library.
>50%	Danshen	Improves circulation, immune system balance/ activity, can often reduce side effects. Studies focus on chemotherapy	At least 500mg daily	Varied studies report impacts of up to 2 or even 3X benefit.	Danshen evidence is focused in chemo, like astragalus its evidence is growing	There is very similar evidence in lung cancers, so yes	Yes	Prescribed doses of 3g per day are typical in first months	Frequently combined with astragalus in clinical studies.Reduces many drug side side effcts.
>50%	Curcumin/Taurine	Good supplement in anti-inflammatory diet	Per supplier. Get a high absorption formula	Very large impact when reduced IL-10 and mIR-21 markers resulted	No current evidence	As in most cancers, high inflammation is a major risk for metastatic activity	Maybe	Yes. Focus trial uses 4x1000mg daily (10mg piperine)/ and 1x500mg taurine	With piperine/ black pepper. This is a single trial but the results are highly compelling, and there are no downside
26-50%	Astragalus	Natural immune system balance and activity, studies are in chemotherapy but also inflammatory marker NLR	At least 500mg daily (50mg astragalaside)	Yes, 40% across multiple trials, and significant reductions in chemotherapy side effects too	Astragalus has good results in chemo and TKI targeted drugs	Yes there is compelling research showing activity in lung cancer	Yes	Prescribed doses of 3g per day are typical in first months	Based on evidence of 2X effects in lung cancer, an excellent natural immune modulator alongside TKIs , eg sorafenib
26-50% or more	Coffee	Coffee has a range of anti-cancer activities in multiple cancers	3 or more standard 8 oz servings	Strong evidence for lower post surgery recurrence, even to the point of complete prevention	Effects are continuous across treatments, and in preventing new tumors after surgery or transplant	No specific evidence for lung tumors	Maybe	in colon cancer, decaffinated coffee had even larger effects	Often caffeine has been proposed as leading the anti cancer benefits, but here decaf had even stronger benefits. Green Coffee Extracts might be interesting (see Supplement Library)
26-50%	Turkey tail	Balance and help regenerate immune system, and reduce side effects	700mg twice daily	Almost 2X reported in late stage oncology. Large data analysis shows more moderate benefit	Not directly but many reports in digestive system cancers	Very likely, there is good evidence in lung cancers too	Yes	Yes trials have used several grams daily	Both dietary mushrooms and mushroom extracts continue to feature in clinical trials for cancer management
26-50%	Beta Glucans	Balance and help regenerate immune system, and reduce side effects	1 or 2x 250mg California Gold Immune Defense with Wellmune	Trials with lentinan from shitakke show about a one third impact	Patented drugs pilot studies in other cancers having good effect	Indirect - there is improved immunotherapy response in lung tumors with beta glucans	Indirectly, lower NLR is linked to lower metastatic activity	As with astragalus	Could alternate with turkey tail. Research studies indicate benefits in managing treatment side effects
26-50%	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	Likely helpful	Yes	Combine wtih supplements	Also read Lifestyle section for view on evidence in diets and eating patterns
Up to 25%	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.	No current evidence	No research on this	Maybe	100mg and even 1g have shown responses in late stage trials	Could alternate with turkey tail. Research studies indicate benefits in managing treatment side effects
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 research on this	Maybe	Trials have used 400mg x3 daily doses	Specific to radiotherapy
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.	Some positive research with citrus pectin has included chemo	Cadmium copper, where present, are known drivers of metastatic activity	Probably	Follow supplier program	Exposure to tobacco may contribute to heavy metal build up. In all cancers having sufficient selenium and zinc is important, including HCC
Indirect - High	Gut health including akkermansia	Indirect importance of gut bacteria is large	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 linked to progression of inflammatory responses	Yes	No, evidence is to apply moderation with supplements	Foundation here is high vegetable and high fiber diet
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 in colon cancer, this seem likely yes	Probably	No data	Ongoing phase III trial looking at reducing treatment side effects especially gastrointestinal....may reduce tumor resistance

Your PATHFINDER brings together research that may increase response and reduce recurrence following surgical procedures including resection or even transplant, including lowering the risk of metastatic spread. And in later stage management with targeted drug treatments such as immunotherapy atezolizumab (Tecentriq) and/or a targeted therapy like bevacizumab (Avastin). Or the tyrosine kinase inhibtors such as sorafenib (Nexavar) for many patients who are unlikely responders to immunotherapy class drugs. To put some perspective on the benefit of using two drugs instead of one this trial shows risk reductions around a third overall https://www.nejm.org/doi/full/10.1056/NEJMoa1915745 While real world data seems to indicate about 20% risk reductions https://www.mdpi.com/2072-6694/17/11/1814, this trial reports a modest 20% or so risk reduction.

The IMPACTS tab summarizes research that and can lead to Many more Good days by helping these treatments work, reducing your risk for progression and by easing treatment side effects. And many have a larger potential effect that 20%. For each of the drug types, 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 “Targeted drugs” 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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