Lymphoma

Research based on patient case data for antihistamine effects shows positive impacts for Hodgkin lymphomas – use of desloratadine leads to much lower risks of progression, specifically in the Hodgkin variant. Similar study of patient records in other cancers confirms superior response rates during immunotherapy, which researchers suggest are also applicable to lymphoma.

The substantial positive impacts found for higher levels of vitamin D3 include an interventional trial that was able to correct levels of this crucial compound in about a quarter of patients. The effects include over 60% improved event free survival during immunotherapy. This would be a much larger effect if comparing full normal levels with clearly deficient patients.

Beta glucans derived from mushrooms or yeast, both commercially available and proprietary forms, are increasingly shown to support oncology treatments including lymphomas. Evidence includes increasing treatment response rates and improving and balancing immune system activity. Re-balancing immune system inflammation levels, the neutrophil-to-lymphocyte ratio and improving low platelet count both reduce risks quite substantially. Along similar lines the well proven herbal supplement, astragalus, is a natural immune modulator with evidence for rebalancing immune system related inflammation. This may help treatment response, and also potentially lower its side effects.

Abnormally high circulating iron in the form of an enzyme like protein called ferritin are closely linked to poor prognosis. Cancers can use ferritin to store iron needed to fuel growth requirements. However, low iron or even anemia is also a big risk found in patient data. The prebiotic classed supplement lactoferrin can counteract the cancer related iron activity, it binds iron in the gut and drives healthy metabolism and balance – so called homestasis. Well balanced ferritin and iron predict much more sustained treatment responses.

Treatment outcomes in lymphomas are heavily influenced by gut microbiome. A high diversity of gut bacteria is reported to improve stem cell therapy success and slowing of progression. Crucially, therapy failure is linked to poor gut microbiota and in particular deficiency or even absence of blautia and akkermansia bacteria. Some necessary oncology treatments reduce levels of these bacteria as do antibiotics.

Successful treatment relies strongly on how quickly new white blood cells can be produced. The Nicotinamide Riboside variant of vitamin B3 has been extensively studied in anti-aging science for its ability to increase cellular mitochondrial health. Now, there are is remarkable pre-clinical evidence that this vitamin can substantially increase stem cell activity that drives production of new white blood cells. Related, another form of B3 has reached phase II for reducing incidence of melanoma in lymphoma and leukemia patients.

A commonly available anti aging supplement, alpha-ketoglutarate, is emerging as a potential supporting role during immunotherapy. Patient data including in lymphoma shows higher levels of responses with increasing levels of AKG, and highly compelling lab studies have confirmed the likely metabolic effects that improve drug activity.

Systemic acute type inflammation is associated with most cancers and resistance to treatment. Supplements including curcumin, garlic and an anti-inflammatory functional food regime are all evidence based interventions, often reported as lowering so called c-reactive protein levels (CRP).

The so called Th1/Th2 immune system balance is strongly linked to the progression of lymphomas 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

Study results show 60% risk reductions with certain antihistamines
Researchers point to desloratadine and probable benefits during immunotherapy
Notably differs from findings in Non-Hodgkin which showed no effects in this dataset.

Our hypothesis is that if these antihistamines are. given together with modern or forthcoming immunotherapeutic agents, the effects could be synergistic or additive and enhance one another. Important to note is also that for this reason, any studies or trials of novel immunotherapies in cancer treatment should take into account this potential antihistamine effect, as antihistamines are often given to alleviate side effects of these therapies, which may introduce confounding into the analyses of such trials and studies

Akkermansia and healthy gut microbiota are crucial to therapy success

Low or no akkermansia and blautia gut bacteria reported with treatment failure
Necessary oncology treatments an antibiotics seen to reduce levels
Diversity of gut microbiota has extensive research showing improved outcomes

Lower microbial gene richness, a lower abundance of the genus Blautia, and a lower abundance of Akkermansia muciniphila, early post-aHSCT was observed in those who developed aGVHD. Myeloablative conditioning was associated with aGVHD along with a reduction in gene richness and abundance of Blautia and A.muciniphila. These results confirm low diversity and Blautia being associated with aGVHD. Crucially, we add that pretransplant conditioning [chemo/radiotherapy] is associated with changes in gut microbiota. Investigations are warranted to determine the interplay of gut microbiota and conditi...

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

An intervention trial of high dose D3 with immunotherapy, level correction and during oncology
Over 90% initially insufficent, which was reduced to around 70%, high BMI limits serum D3 levels
Over 60% improved event free survival reported, and that was conservative

We analyzed the impact of 25(OH)D levels on event-free survival in patients treated with Rituximab… 25(OH)D levels below 20 ng/mL at diagnosis and IPI were independently associated with inferior EFS. Moreover, patients with normalized 25(OH)D levels following supplementation showed better EFS than patients with persistently deficient/insufficient 25(OH)D levels. Our study provides the first evidence that achievement of normal 25(OH)D levels after vitamin D3 supplementation is associated with improved outcome in patients with DLBCL and deficient/insufficient 25(OH)D levels when receivi...

Alpha Ketoglutarate is emerging in oncology particularly for enhancing immune system activity during immunotherapy

Lymphoma tumors cells upregulated glutamine and low alpha-ketoglutarate levels drive growth
Increasing AKG levels strongly recuce glutamine uptake with very striking results in a mouse model
Effects in health and anti-aging science show metabolic and anti-inflammatory benefits

Notably, glutamate, glutamine, and α-KG were the critical metabolites in glutamine metabolism. Clinical data analysis identified that high glutamine concentrations and low decreased α-KG were associated with poor prognosis in DLBCL patients. Subsequently, dimethyl α-ketoglutarate (DM-αKG) was used to reverse glutamine metabolism and increase α-KG concentration. In vitro studies showed that DM-αKG treatment significantly inhibited cell proliferation of DLBCL cells both in vitro and in vivo

Beta glucans protect and balance immune system activity improving outcomes

Around 1/3 of patients show significantly increased immune system activity
Evidence suggests at least a supportive role in immune system health
One patent of 20 is reported with direct anti-cancer response

In this study, twenty patients with advanced malignancies receiving chemotherapy were given a β-(1,3)/(1,6) D-glucan preparation (MacroForce plus IP6, ImmuDyne, Inc.) and monitored for tolerability and effect on hematopoiesis. Our results lead us to conclude that β-glucan is well-tolerated in cancer patients receiving chemotherapy, may have a beneficial effect on hematopoiesis in these patients and should be studied further, especially in patients with chronic lymphocytic leukemia and lymphoma.

Vitamin B3 in several forms shows protective effects in cancers

Vitamin B3 variant accelerates activity of hematopoietic stem cells
Large protective effect in mouse model gave dramatically higher survival
B3 is widely available and has supporting evidence in other cancers

NR dietary supplementation results in a significantly enlarged pool of progenitors, without concurrent HSC exhaustion, improves survival by 80%, and accelerates blood recovery after murine lethal irradiation and limiting-HSC transplantation….Our work demonstrates for the first time a positive effect of NAD⁺-boosting strategies on the most primitive blood stem cells, establishing a link between HSC mitochondrial stress, mitophagy, and stem-cell fate decision, and unveiling the potential of NR to improve recovery of patients suffering from hematological failure including post...

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

Lower ferritin levels seen halving the relative risks
Around a 60% effect on risk for recurrence and progression
High ferritin strongly linked to relapse prior to stem cell therapies

Elevated serum ferritin is associated with reduced survival following allogeneic transplantation and an increased risk of toxic and infectious complications after autologous hematopoietic stem cell transplantation. We studied 315 patients who underwent ASCT for Hodgkin (HL) or non-Hodgkin lymphoma (NHL) at our institution in whom pretransplantation ferritin was available to determine its association with survival. On multivariate analysis, a pretransplantation ferritin >685 ng/mL was associated with significantly lower overall and relapse-free survival, Ferritin >685 ng/mL was associa...

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

Immune system inflammation marker NLR linked to progression
Low levels are reported to reduce overall risks by 70%
Astragalus has evidence here and with low platelet count

The accumulation of neutrophils is related to increased cytokine levels, especially IL-8 and it has been suggested that a high number of neutrophils may actually promote tumor growth and metastasis and/or inhibit lymphocyte activity, thereby counteracting the antitumor immune response . These observations suggest that an imbalance in the ratio of neutrophil to lymphocyte in the peripheral blood of patients with cancer may be related to tumor development…Our single center study clearly showed that high NLR is associated with shorter overall survival in patients with newly diagnosed HL....

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

Inflammatory immune response increases treatment resistance
80% reduction in relapse with low inflammation at the 6th round of chemo
Underpowered for reporting effects on overall risks and benefits

High CRP levels were associated with advanced disease and presence of B symptoms. CRP was considered a predictor of treatment response after the 5th and 6th cycle of chemotherapy, while persistent high CRP levels during treatment were associated with refractoriness….Our results show that baseline CRP level was higher in patients with advanced disease and B symptoms. Level of CRP was associated with final response to treatment, showing that patients with persistent high serum CRP during treatment should be assessed carefully for potential poor response. CRP holds promise for widespread...

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GUIDE

Pathfinder Element	Risk Reduction Factor	Anti-Metastatic	Reduces Side Effects	Research Study
Antihistamines	>50%	Probably	Probably	Link
Vitamin D3	>50%	Yes	Maybe	Link
Beta Glucan	Up to 25%	Yes	Yes	Link
Astragalus	Indirect - High	Yes	Yes	Link
Gut microbiome / Akkermansia	Indirect - High	Probably	Yes	Link
Lactoferrin	Indirect - High	Probably	Yes	Link
Vitamin B3	Indirect - High	Maybe		Link
Alpha ketoglutarate	Indirect - High		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

Hodgkin class lymphomas are commonly managed with chemotherapy, often combined with radiotherapy. In progressing disease there can be an addition of targeted drugs and immunotherapy. Some cases are addressed with stem cell therapies.

Your PATHFINDER brings together research that may help slow down early phase progression considerably. And, with advancing disease, maximize the effects of chemotherapy, targeted drug treatments 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 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, so called “extranodal” progression, 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

Lymphoma

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