Bladder

Bladder cancer tends to be less frequently researched, but despite this there are some opportunities to increase treatment results and quality of life. Several well proven widely available supplements or over the counter drugs can be effective in supporting oncology. Impacts may even exceed those of adding in some of the emerging oncology drugs, but reducing rather than increasing the risks for side effects.

Large scale analysis of patient case records in scandinavia show that antihistamines, particularly desloratadine, reduce progression risk. Bladder cancer has recently been reported reponding to the improved immune system activity from anti-histamines during immunotherapy. Also well known for immune system health benefits is vitamin D3, which is often deficient in cancer patients, leading to poor prognosis. Recent studies in bladder cancer patients find risk levels are halved with higher levels of D3 during treatment. Also reported by most research are the lower risks of both cancer and all cause mortality. Also related to all cause mortality, danshen a widely used chinese herbal extract is reported to support improved cardiovascular health. Danshen has a variety of evidence in other cancers for improving patient outcomes.

Many cancers will fuel growth by upregulating fatty acid metabolism which can be seen in certain biomarkers. Studies in bladder cancer certainly report increases in these biomarkers for dysfuntional fatty acid (lipid) absorption, and links levels of these to both faster progression and metastatic spread. Of many natural compounds that help regulate lipids and fatty acids, berberine is perhaps one of the more prominent, including some commercial branded supplements adding other ingredients. Similarly, systemic inflammation is often a feature of cancer activity, and in bladder cancer large scale analysis links low inflammation to a 50% reduced overall patient risk for progression. Several supplements can assist an anti-inflammatory healthy diet plan including curcumin (with piperine). Consider a high absorption formula.

Also frequent in poor bladder cancer prognosis is iron deficiency even anemia, combined with upregulated and dysfunctional iron uptake by tumors. These risks are large and re-balancing iron can be important to maximize treatment success and reduce these risks. Milk protein supplement lactoferrin helps correct anemia and increase red blood cells counts and may inhibit cancer related iron activity. Another heavy metal increasingly shown to drive progression is copper, and in bladder cancer. Low copper levels are shown to significantly decrease risk of progression. Citrus Pectin based supplements can detoxify heavy metals and bring potentially beneficial any cancer activity of its own.

Inflammatory response from the immune system can increase all cause mortality risk and treatment resistance, In this area, chinese and also turkish oncology has shown that danshen and astragalus extracts have protective effects on immune system health contributing to substantially reduced all cause risks in vascular health as well much improved outcomes from immunotherapy. The so called Th1/Th2 immune system balance is strongly linked to the progression in bladder cancers, and to treatment resistance. Molecular iodine solutions are emerging in this area in breast cancer management, seen boosting Th1 anti tumor activity and helping suppress over active Th2 used in resistance. This has improved results in surgery plus chemotherapy and may support increased responses during 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

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

Relative risk reductions for progression about 40% lower during immunotherapy
Progression free time from treatment was also about 30% longer in relative terms
Aligns with 25% reported risk reductions from large scale study of patient records

In conclusion, using individual patient data from the IMvigor 210 and 211 trials, we found that concomitant use of antihistamines was associated with prolonged progression-free, cancer-specific and overall survival in patients treated with atezolizumab. Our results showed a positive association between antihistamines use and oncologic outocmes in patients with mUC treated with IO. This effect deserves further prospective investigation

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

About a third lower progression risk with (low dose) aspirin reported
Similar study shows all cause mortality also 30% improved
Suggested mechanism is inhibiting so called COX2 enzyme driven inflammation

We did not observe any significant associations between aspirin use and cancer incidence, although we observed a significant association between aspirin use and bladder and breast cancer survival. Although aspirin use at least 3 times/week was associated with the strongest risk reduction, any aspirin use was associated with increased bladder and breast cancer survival. These results may indicate that for some cancer types, any aspirin use may be advantageous; however, greater benefit may be observed with increased frequency of use.

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

Large scale analysis of patient records and outcomes
Risk of major adverse cardiovascular events reduced 44% with danshen
A 40% reduced risk for all cause mortality and also reported

In this study, we found that Danshen use was associated with a 40% decrease in mortality and a 44% reduction in MACE [major adverse cardiac event] compared with those in the TCM and non-TCM groups. Compared to previous studies on Danshen’s effects on cardiovascular outcomes in cancer patients, our findings provide a more comprehensive understanding, especially in the context of bladder cancer. Patients with bladder cancer treated with Danshen showed a significantly lower incidence of MACE and improved survival rates.

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

A study of over 100 patient cases shows clear advantage in those with higher vitamin D3
Even being above the modest cut off level here sis reported to reduce progression risk about a half
Interventional trials in other cancers are showing early signs of success with higher doses of D3

Locally advanced and metastatic Bladder Cancer has a poor prognosis for various reasons, and it is critical to identify prognostic and predictive variables for this patient population. In this cohort study, circulating vitamin D levels before platin-based chemotherapy was associated with improved OS in patients with locally advanced or metastatic BC…We emphasized that low serum vitamin D levels may be a predictive value in our patients with BC by showing the relationship of poor survival

Berberine is a potent regulator of metabolic health including fatty acid metabolism

Upregulated fatty acid metabolism is reported and biomarkers proposed
The specific upregulated protein activity is linked to both progression and spread
Berberine is well documented for its ability to improve fatty acid metabolism

Bladder Cancers generally expressed significantly higher levels of the carnitine palmitoyltransferase 1A (CPT1A) than control tissues . Carnitine palmitoyltransferase is a key protein that uses carnitine to transfer fatty acid into mitochondria for oxidation. In addition, the increase was more significant in MIBC [metastatic] than NMIBC, and its level was different significantly between the two types of cancer. Therefore, carnitine palmitoyltransferase 1A (CPT1A) expression may also correlate with the aggressiveness of BC… Supporting it is that in highly metastatic alveolar rhabdomyos...

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

Patient data shows increased iron storage in bladder cancer
Increased iron metabolism is linked to disease progression
Anemia is also common in bladder cancer and doubles risks

We demonstrate for the first time that hepcidin is expressed in bladder cancer tumors, probably due to infiltrating macrophages. Furthermore, we show that high hepcidin expression and low ferroportin-1 expression is associated with poor patient survival. Our data indicate that hepcidin is up-regulated in bladder cancer tissue by an IL-6 independent pathway. The triggering factor for the elevated expression of hepcidin in bladder cancer tissue is unclear, however, hepcidin might represent a novel pro-oncogenic signaling mechanism.

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

Bladder cancers upregulate copper availability to increase growth
Here SLC31A1 signaling pathway is found in patient data increasing copper
40% lowered progression risks are shown for lower relative copper activity

We observed that SLC31A1 was significantly up-regulated at both the mRNA and protein levels in bladder cancer tissue samples, suggesting its potential involvement in bladder cancer development and progression. Furthermore, our investigation into the methylation status revealed that SLC31A1 was significantly hypomethylated in bladder cancer tissues, which may contribute to its overexpression. The ROC analysis of the SLC31A1 gene indicated promising diagnostic potential emphasizing its relevance in distinguishing bladder cancer patients

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

Lower inflammation levels halve the all cause mortality risk
Similar benefit reported for progression free time
Systemic inflammation can affect therapy response

The efficiency of CRP in predicting BCa prognosis has been previously analysed, but there are no consistent findings. In this study, we synthesized data from 20 articles involving 7276 cases. Our pooled data showed that CRP level significantly predicted the dismal OS, CSS, RFS and PFS of patients with BCa. Moreover, the prognostic power of CRP was stable in the subgroup analysis….Collectively, CRP levels significantly and reliably predicted the short- and long-term prognosis of patients with BCa

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

Increased immunotherapy success with lower neutophil-to-lymphocyte ratio
Over 60% reduced risk of recurrence linked to lower NLR levels
Astragalus has shown evidence of balancing immune system inflammation

Our research findings indicate that elevated preoperative NLR levels are a promising and cost-effective prognostic biomarker for recurrence and progression in patients with NMIBC with intravesical BCG immunotherapy. To the extent of our knowledge, this is the first meta-analysis to comprehensively examine the relationship between preoperative NLR levels and the risk of recurrence and progression in patients with NMIBC who underwent intravesical BCG immunotherapy. In patients with NMIBC receiving intravesical BCG immunotherapy after TURBT, the combined results showed a significant correlatio...

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GUIDE

Pathfinder Element	Risk Reduction Factor	Anti-Metastatic	Reduces Side Effects	Research Study
Vitamin D3	>50%	Yes	Maybe	Link
Danshen	26 - 50%	Yes	Yes	Link
Antihistamines	26 - 50%	Probably	Probably	Link
Aspirin	26 - 50%	Yes	Maybe	Link
Astragalus	Indirect - High	Yes	Yes	Link
Lactoferrin	Indirect - High	Probably	Yes	Link
Citrus Pectin	Indirect - Moderate	Probably	Yes	Link
Berberine	Indirect - Moderate	Maybe	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

Bladder cancers can initally be treated with some combination of surgery, radio and/ or chemotherapy. Either at this stage or due to progression, immunotherapy drugs such as pembrolizumab (Keytruda) or avelumab (Bavencio) may be recommended and have shown overall risk reductions in the range of a third or so. More specific targeted drugs might also be included in that list due to progression.

Your PATHFINDER brings together research that may help slow down early phase progression considerably, including reducing metastatic spread and recurrence. And, with advancing disease, maximize the effects of chemotherapy or immunotherapy. 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, 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 “Targeted drugs” 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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