Notice

This blog post provides information about micronutrients and aims to encourage responsible self-management of health issues. It is expressly not intended as a substitute for medical advice, diagnosis, or treatment. Like any science, nutritional science is constantly evolving. Therefore, the author and Qidosha GmbH cannot assume any liability for information regarding dosages, methods of application, or any inaccuracies. Any application is at the user's own risk.

Cancer as a multifactorial disease of the entire body

Cancer is not merely a disease of an organ, but can be disease of the whole body The entire metabolic process is involved in its prevention, establishment, and progression. Its development represents a complex, multi-stage process that can take place over many years and depends on a great many factors. (See figure below). The development of malignant tumors involves a combination of endogenous and exogenous factors, with varying frequency, involving metabolic dysfunctions or overloads. The sum of these factors initially leads to qualitative and quantitative changes in the structure and function of individual cells, and subsequently to more extensive damage from which malignancies can develop. So-called proto-oncogenes, which promote malignant transformations, and suppressor genes (z.B. Control genes, repair genes), which inhibit the remodeling, are associated with the development of cancer.

Genetic factors are, according to current knowledge, on average only responsible for approximately 5.5% of cancer cases, but may occur more frequently in certain tumors, so z.B. in carcinomas of the prostate (15.3%), colon (10.1%) and breast (8.3%).

Inflammation and infections also play a significant role in the development of cancer. The majority of malignant tumors are attributable to exogenously mediated environmental and lifestyle factors., How z.BExposure to biological, physical and chemical noxious agents, physical and psychological stress, iatrogenic measures (z.BIonizing radiation), obesity and poor diet, or abuse of everyday drugs (such as nicotine and alcohol). Risk factors for the development of prostate cancer include: z.B- in addition to genetics - overweight, a diet high in "unfavorable" fats, alcohol, lack of exercise and low sexual activity are recognized as contributing factors.

Furthermore, if the damaged cells themselves are to multiply and later develop into cancer, they must possess special properties that enable survival in a "hostile environment." These include the ability

• to remain invisible to the immune system (including repair mechanisms and apoptosis) for as long as possible.
• to build up their own blood supply or to form new blood vessels (angiogenesis)
• to survive in a hypoxic environment
• to migrate from a cell cluster and form metastases

In order to truly "defeat" or even just suppress cancer, we must intensively study the aforementioned causes of cancer development and the factors that promote or inhibit cancer growth..

To do this To prevent the development of cancerThe body possesses various effective defense mechanisms that, in the event of danger, operate in a cascade-like fashion and complement each other. These include

• the Detoxification from risk factors (z.B. pollutants, radicals) and
• the Prevention of mutations as well as
• the Repair or removal or killing of damaged cells

Therefore, cancer usually only develops when – in addition to the increased burden from endogenous and exogenous risks – the body's own resources are overwhelmed or fail.

The following are important for the success of the repair measures: u.a.:

• a well-functioning metabolism (including energy production in the mitochondria)
• a good detoxification performance
• a fine-tuning of the cellular (v.a. T lymphocytes) and humoral (v.aAntibodies) Components of the immune system
• the influence on inflammation and latent acidosis as well as
• the reduction of the occurrence of free radicals

The 3 phases of cancer

Cancer development is now divided into three phases.

1. Cancer initiation
2. Cancer PhD
3. Cancer progression

Each of these phases also includes the o.gFactors such as oxidative stress, changes in energy balance, infections, or chronic inflammation are involved, which is why considerations regarding the influence of these functional circuits must be incorporated into future concepts.

At the Cancer initiation One or more healthy cells change, and if they are not repaired or destroyed, they serve as "cancer stem cells," which, under favorable conditions, can transform into active cancer cells over time and multiply uncontrollably. This is caused by damage to the mitochondrial or nuclear DNA due to unfavorable genetics or—more frequently—by one or more other factors (z.B(Carcinogens, infections, oxidative stress). Chemical carcinogens such as polycyclic aromatic hydrocarbons are z.BMetabolized to reactive species, tumor-promoting substances promote the expression of genes whose products have pro-inflammatory effects. This includes, above all, the modulation of the expression of growth factors and cytokines. In particular, activator protein 1 (which controls various cellular processes such as differentiation, proliferation, and apoptosis) and NF-κB (a transcription factor stimulated by TNF-α and interleukin-1 during the immune response) are affected. v.a(which is of great importance in the regulation of the immune response, cell proliferation, and apoptosis) and other transcription factors are closely linked to inflammatory and immune responses, as well as to the regulation of cell proliferation and programmed cell death. These processes also block the body's own protective and repair mechanisms, which are crucial for preventing cancer initiation. The genetic damage in the cell is passed on to daughter cells.

If “pro-cancer” factors are present (z.BIf the body's natural repair mechanisms (e.g., inflammation, growth factors, hormones) and the initiation of programmed cell death for the disposal of cancer cells fail to function, the cancer cells multiply and the tumor grows. This is then referred to as the phase of Cancer PhD.Activator protein-1, NF-κB, and other transcription factors involved in regulating cell proliferation and programmed cell death also play a role here. Inflammation induces z.BNF-κB, which in turn activates survival genes in the cell and contributes to uncontrolled cancer cell growth and metastasis. Macrophages also produce substances that stimulate tumor growth, including TNF-α, which itself boosts NF-κB activity.

After a usually longer period of time (typically between 2 and 30 years), the third phase of cancer development occurs, the phase of Cancer progression, in which the tumor grows. This can lead to – in this case undesirable – new blood vessel formation (angiogenesis) and ultimately to metastasis. Increased angiogenesis ensures the tumor's energy supply and facilitates its spread. Other key promoters of tumor growth and progression are accelerated cell growth and a renewed failure of programmed cell death, which is significantly influenced by various pro- and anti-apoptotic factors. These include z.B. the tumor-suppressing caspases as well as the transcription factor p53, the p53-induced cell cycle inhibitor p21 and various tumor-promoting substances such as protein kinases and cyclins.

Development of cancer

Metabolic cycles and cancer

Cancer itself, its associated effects, and the therapeutic efforts all change us in general, and our bodies, particularly our metabolism, in particular. Metabolic dysfunctions, in turn, further exacerbate the diverse negative effects of cancer and its treatment on the body.

a) Detoxification function and cancer

Our bodies have to deal with many endogenous and exogenous, or rather diverse, chemical, biological and physical pollutants every day. V.aExposure to exogenous pollutants is increasing sharply, and it is particularly problematic that we cannot detect many of these pollutants, and even small individual amounts can accumulate to cause significant overall harm. Most pollutants are carcinogenic and must therefore be detoxified as quickly as possible before they can cause damage. This occurs through a multi-stage detoxification program, primarily in the liver, where the pollutants are first processed, functionalized, and conjugated for excretion. We must therefore ensure that the body's detoxification and elimination processes function optimally..

b) Oxidative stress and cancer

Free radicals are formed in varying types and quantities depending on individual lifestyle, genetics, and metabolic status through a variety of exogenous and endogenous processes. They generally have a negative impact on metabolism and are u.a. recognized as a cause of damage to mitochondrial DNA and cellular DNA or to other structures (z.B. p53), which then often leads to cancer. Furthermore, free radicals can promote the release of pro-inflammatory cytokines and impair both immune function and energy metabolism. Therefore, in addition to the Prevention of the formation of harmful radicals from endogenous and exogenous sources as soon as possible Elimination of unavoidable radicals.

One exception to this rule exists z.B.During oncological chemotherapy and radiation therapy, the goal is sometimes to kill tumor cells through the formation of free radicals. Unfortunately, an unpleasant side effect is that healthy cells are also damaged. Therefore, academic and complementary oncology should work together to find ways that, on the one hand, do not hinder the desired effects of free radicals on the cancer, and on the other hand, prevent damaging effects on healthy cells. This is feasible, but requires a very well-structured approach for implementation in individual patients.

c) Inflammation and cancer

Inflammation is now recognized as an important player in the development of cancer and many other diseases, although according to current scientific standards Acute inflammation tends to have a protective effect, while chronic inflammation promotes the development of cancer.It is assumed that Approximately 15-20% of all cancers are partly caused by inflammation. (See study examples). A middle ground must therefore be found between promoting beneficial inflammation and minimizing harmful inflammatory processes; in particular, undesirable chronic inflammation must be avoided or terminated using the gentlest possible methods.

d) Immune system and cancer

Medical literature repeatedly states that up to 20% of all cancers are partly caused by infections or a weakened immune system (see study examples). The immune system should act as a strong, natural guardian against cancer threats. Its primary task is to... chronic inflammation (z.B. chronic hepatitis) or biological pollutants (z.B. oncogenic viruses such as EBV, HHV-8, HTLV or HPV) to eliminate and prevent mutations in advance of any resulting changes in body cells.For this to happen, the immune system must function optimally and detect these dangers as completely as possible. This is z.B...is hardly possible with a (even therapeutically) suppressed immune system. Next, the immune system must... Destroy degenerated and irreparable body cells. This is more difficult because damaged cells are also the body's own cells, and initially their antigens are not recognized by the immune system. However, since damaged cells can trigger inflammation, and certain tumor-specific antigens can arise through genetic reprogramming or oncogenic viruses, they are often eventually presented to the immune system for destruction.

The defense against tumor cells is roughly equivalent to the fight against intracellular pathogens. Tumor cells are destroyed by cytotoxic T cells.which can trigger apoptosis with the support of T helper cells, B cells and their antibodies, as well as NK cells and the complement system. And ultimately, the immune system must be able to the body weakened as part of cancer therapy z.Bto protect against the uncontrolled proliferation of remaining cancer cells or against new infectionsThis is why any disease- or therapy-related immunosuppression must be eliminated quickly and with minimal side effects. This is made more difficult by the fact that the tumor defends itself against the immune system and attempts to evade its surveillance by forming a "camouflage network." Tumor cells divide very rapidly, frequently mutate spontaneously, and constantly change their properties. Furthermore, the immune system often already exhibits tolerance to tumor antigens at the level of CD4 and CD8 T cells.Tumors also produce cytokines such as TGF-β or IL-10, which reduce inflammation and create tolerance to T cells, or they produce increased amounts of IDO (indoleamine 2,3-dioxygenate), which leads to tryptophan deficiency (which in turn impairs the function of T cells), as well as FASL (ligand of member 6 of the TNF receptor superfamily), which causes apoptosis of T cells.

University oncology departments are therefore attempting to mobilize the immune system against larger, already visible tumors. However, this has so far only been partially successful, partly because the immune system seems unable to attack or even destroy larger tumors. Oncologists hope, however, that at least micrometastases or residual tumor cells remaining after basic therapy can be eliminated by an optimally functioning immune system. Tests are being conducted to explore this. u.aPassive immunization with monoclonal antibodies or activation of the complement system, NK cells, or macrophages against components of tumor cells. Antibodies are also used to increase the number of T cells against tumor antigens and of NK cells, as well as to reduce VEGF (vascular endothelial growth factor), which promotes the formation of new blood vessels. For late, non-specific activation of the immune system in already diagnosed tumors, z.BThe use of cytokines such as TNF-α, IL-2 or IFN-α has been tested.

However, it is probably insufficient to strengthen the immune system of an already ill person in late-stage therapy (i.e., at the point when university-based interventions typically begin to take effect) with potentially burdensome medications. Instead, the immune system should be modulated well in advance through prevention and early treatment using gentle activities. z.B. by means of an “immune boosting program” with micronutrients, the humoral and cellular immune system is strengthened - to protect against degenerated cells and their later negative consequences.

e) Energy balance and cancer

According to a theory by Warburg (1883-1970), which has since been confirmed several times, Can cancer cells also obtain their energy through the fermentation of sugar (aerobic glycolysis) in the cell cytosol?In this case, they largely forgo the combustion of oxygen to CO2 and H2O in the mitochondria, as well as the use of fats or proteins as an energy source. Glycolysis can occur via two pathways: the so-called "Embden-Meyerhof pathway" and the pentose phosphate pathway, in which the enzyme transketolase-like-1 (TKTL1) plays a crucial role. u.a...is controlled by the amount of TKTL1 produced. The additional glycolysis via the pentose phosphate pathway allows the tumor cell a higher energy yield.

During fermentation, the cancer cell requires 20 to 30 times the amount of sugar required for oxygen combustion in the mitochondria to obtain sufficient energy.Unlike normal cells, which usually only use fermentation when oxygen is scarce, cancer cells actually use it even in the presence of oxygen. Due to increased lactate production when glycolysis is predominantly used, the tissue surrounding the tumor becomes acidified, which can lead to a disruption of the entire metabolism and also to an improvement in the survival chances of cancer cells and an increased risk of resistance to chemotherapy and radiation therapy..

Therefore, attempts should be made to inhibit energy production via fermentation in tumor cells in order to slow the growth of tumor cells and to make cancer cells more sensitive to therapy.Furthermore, the inhibition of fermentation should be combined with the inhibition of ATP production in tumor cells in order to increase the chances of apoptosis and necrosis as well as sensitization to other therapeutic measures.

Tumor-specific risk factors

In cancer prevention, it is important to have precise knowledge of individual risks. Therefore, in addition to the generally applicable risk factors, it seems necessary to know as many specific, recognized risk factors for individual tumor types as possible, the presence of which suggests early therapy is advisable. These specific factors can z.BFurther information can be found in the various oncological guidelines or at the German Cancer Aid (Blue Guides, Your Cancer Risk). The most well-known of these factors are listed in the following tables.

factor	Colorectals carcinoma	Breast Cancer	prostate Cancer	lung	uterus (Cervix, endometrium)
Frequency in % (Ø)	16	29 w	24 m	7 women, 14 men	3 or 6 w
alcohol abuse	X	X	-	-	-
Old	&40 years	&50 years	> 50 Years	-	&50 years
Medical history Malignant tumors	X	X	-	X	-
Diabetes mellitus	-	-	-	-	X
Inflammatory Diseases	Inflammation of the intestine	-	Prostatitis	-	-
Unbalanced diet, heavy on meat, low in fiber	X	-	X	-	-
Nutrition (more than 1 liter Milk per day)	X	-	X	-	-
genetics	Family Polyposis	approximately 5% (above all BRCA-1, BRCA-2)	approximately 5-10 %	X	approx.5-10% (z.B. HNPCC syndrome)
Gender	-	X	X	-	X
Infections	-	-	-	-	Sexually transmitted HPV
Immunosuppression	-	-	-	-	X
Childlessness	-	-	-	-	X
Medications	-	hormone Substitute Therapy, calcium antagonists	-	-	Estrogens, tamoxifen, Aromatase inhibitors
Early menarche, Late menopause	-	-	-	-	X
Nicotine abuse	X	X	-	XX	X
Polyps, cysts	Intestinal polyps	-	-	-	Ovarian cysts
race	-	-	Black	-	-
Pollution	-	-	-	z.BAsbestos	-
Shift work (especially with Night work)	X	X	X	X	-
Sexual partner changing	-	-	-	-	X
Radiation exposure (z.B.through diagnostic or therapeutic (Medicine, Profession)	-	X	-	X	X
Overweight	X	X	X	-	X

factor	bladder	Malignant Melanoma (Skin)	Head Neck Tumors	pancreas	No Hodgkin Lymphoma	leukemia
Frequency in % (Ø)	4 w, 8 m	1 female, 3 males	3	3	3	3
alcohol abuse	-	-	X	-	-	-
Medical history Malignant tumors	-	X	-	-	-	-
Diabetes mellitus	-	-	-	X	-	-
Inflammatory Diseases	Inflammation of the bladder	-	-	Inflammation of the pancreas	-	-
Unbalanced diet, heavy on meat, low in fiber	X	-	-	-	-	-
genetics	-	X	-	X	-	-
Skin nevi	-	X	-	-	-	-
Immunosuppression	-	X	-	-	-	-
Infections	-	-	Eppstein Barr	-	Eppstein Barr	HTLV
Medications	Cyclophosphamide, Phenacetin	arsenic	-	-	-	Cytostatic drugs, Immunosuppressants
Oral hygiene lacking	-	-	X	-	-	-
Nicotine abuse	X	-	X	X	-	X
race	-	Fair skin	-	-	-	-
Pollution	z.B. aromatic Amines	-	X	-	-	X
Shift work (especially with Night work)	X	-	-	X	X	X
Radiation exposure (z.B.through diagnostic or therapeutic (Medicine, Profession)	-	UV light	X	-	-	X
Radiation exposure (Living within from 5 km to Nuclear power plant						X

factor	ovaries	testicles	liver	stomach	kidney
Frequency in % (Ø)	5 w	2 m	&<1	4	4
alcohol abuse	-	-	X	X	X
Old	X	-	-	-	-
Medical history Malignant tumors	-	X	-	-	-
Cystic Kidney disease	-	-	-	-	X
Iron storage disease	-	-	X	-	-
Inflammatory Diseases	-	-	-	gastric mucosa	-
Unbalanced diet, heavy on meat, low in fiber	-	-	-	-	X
Birth weight low	-	X	-	-	-
genetics	X	X	-	X	X
Gender	-	X	-	-	-
Undescended testicles	-	X	-	-	-
Infections	-	-	Hepatitis, Molds	Helicobacter pylori	-
Childlessness	X	-	-	-	-
Liver cirrhosis	-	-	X	-	-
Medications	-	-	-	-	Painkillers
Nicotine abuse	-	-	-	X	X
Estrogen levels ↑ (Mother or husband)	-	X	-	-	-
Reflux esophagitis	-	-	-	X	-
Pollution	-	-	X	X	X
Overweight	-	-	-	-	X

factor	throat larynx	thyroid	esophagus	penis
Frequency in % (Ø)	1-2	2 w, 1 m	1 female, 2 males	&<1
alcohol abuse	X	-	X	-
Diabetes mellitus	-	-	-	-
Unbalanced diet, heavy on meat, low in fiber	X	-	-	-
genetics	-	X	X	-
Infections	-	X	-	HPV
Oral hygiene lacking	X	-	-	-
Nicotine abuse	X	-	X	-
Reflux esophagitis	-	-	X	-
Pollution	X	-	-	-
SD node cold	-	X	-	-
radiation exposure (z.B.(through diagnostic or therapeutic medicine, profession)	-	X	-	-
Overweight	-	-	X	-

Cancer risk factors and cancer types that these factors preferentially trigger

If, after reviewing the basic data, we want to decide on "early cancer therapy" at a point when the tumor is still too small to be generally visible, tumor markers, ultrasound examinations, or whole-body CT scans often do not provide reliable results at a very early tumor stage. However, laboratories in particular offer a large number of further diagnostic parameters that can be used in u.gThe tables are listed.

measure	parameter	To use
General laboratory screening	ESR, blood count, creatinine, blood glucose Uric acid, protein electrophoresis, LDH, GOT, GPT, y-GT, AP, SP, TSH, K, Na, Calcium, Fe, HDL, LDL, Triglycerides, urinalysis	General information and screening for organ dysfunction and tissue breakdown
Immunoscreening (initial, tumor phase I)	Differential blood count including granulocytes Monocytes, lymphocytes (cellular), Immunoglobulins IgA, IgG, IgM, IgE (humoral), TH1/TH2 balance	It primarily measures the quality of Defense says little about Tumor-specific defense (since Tumor cells, at least initially (usually disguised)
Immune system advanced (Tumorphase II)	Lymphocyte differentiation, B cells, T cells, T helper cells, Naive helper cells, memory cells, IL-2 expressing helper cells, T-suppressor cells, NK cells, T-cytotoxic suppressor cells, activated killer cells, neopterin, CD 25, CD 69, TGFβ	Indication of tumor-associated changes in immunocompetence and assistance in therapy decisions and monitoring.
Inflammation screening	hsCRP, TNFα, histamine, IP-10 IL-1, IL-6, NFkB	Indications of acute or chronic inflammation
Detoxification screening Advanced detoxification	GSH (intracellular) Paracetamol and caffeine metabolite test GSH/GSSG	Indications of the quality of the detoxification function
Screening oxidative-nitrosative stress Oxidative-nitrosative stress advanced	MDA-LDL, Nitrotyrosine Antioxidant capacity (TAS), Hydroperoxides, antioxidants, lactate pyruvate, methylmalonic acid, 8-OH-Deoxyguanosine	Indications of radical damage and antioxidant capacity
Acid-base screening Acid-Base Advanced	Urine pH daily profile using test strips Sander titration	Indications of acidosis
Bowel function screening Advanced bowel function	Intestinal flora analysis, zonulin (Serum marker for intestinal permeability) Antitrypsin (Inflammatory markers in stool)	Indications of bowel function
Neuroendocrine screening Neuro-endocrine function advanced	Cortisol daily profile (saliva), Norepinephrine, serotonin Tryptophan, tyrosine, dopamine, DHEA	Indications of the function of the Neurotransmitter metabolism
Mitochondrial screening advanced mitochondria	ATP L-Carnitine, Coenzyme Q10	Indications of the function of Mitochondria
Tumor nutrition	TKTL1	Note on the Energy generation in the tumor
Micronutrient diagnostics	z.B.Zinc and iron (low levels) (indicate tumor activity) Copper and ferritin (high levels) (indicate tumor activity) Selenium, Vit B12, Vit B2, glutathione, Homocysteine, folic acid	Signs of undersupply and imbalance as well as on Tumor activity
Bleeding diagnostics	Hemoglobin-haptoglobin in stool Erythrocytes in urine	Signs of microbleeds

What can be useful for a tiered, oncology-oriented laboratory diagnostics approach in practice?

measure	To use
TPA (tissue polypeptide antigen) Tumor-associated proliferation antigen	Non-specific tumor marker, Independent of primary tumor and generally applicable
Mutation of the p53 gene	Apoptosis capacity is nonspecific (prognostic factor for various tumors)
p53 autoantibodies	Non-specific tumor marker positive in 10-30% of tumors (healthy cells are p53 autoantibody negative)
Apo10 antigen	Non-specific tumor marker (healthy cells are Apo10-negative), which provides evidence of disorders of apoptosis in tumor cells
Cyp1B1 enzyme (from the cytochrome p450 family)	Non-specific tumor marker (According to Dr. Dan Burke, healthy cells are Cyp1B1-negative)
Chemosensitivity test	Tumor tissue is treated with medication to reduce its reactivity. to find the substance that is best suited to each tumor
CEA (carcinoembrional antigen) tumor-associated antigen	Highly specific, especially for colon cancer (80%), and less. specific for pancreatic cancer (60%), breast cancer (55%) and Biliary tract and bronchial cancer (50%) o.aTumors
PSA (prostate-specific antigen) Tissue-specific antigen	At V.aProstate cancer
TG (thyroglobulin), hCT (human calcitonin)	At V.a Thyroid cancer
AFP (α1-fetoprotein)	At V.aLiver cancer, teratoma
AFP and HCG (human) Chorionic gonadotropin	At V.aGerm cell tumors (testes, ovaries)
CA 72-4	At V.aStomach cancer, breast cancer
Monoclonal immunoglobulins and Bence-Jones proteins	At V.amultiple fibroids
CA 19-9, CA 195, TPA	At V.aPancreatic cancer
CA 15-3, CA 549, MCA (Mucin-like Carcinoma Associated Antigen	At V.a.Breast cancer
CA 24, CA 50	At V.aIntestinal cancer, pancreatic cancer
CA 125	At V.aStomach cancer
NSE (neuron-specific enolase)	At V.aBronchial carcinoma, neuroblastoma
CYFRA 21-1 (cytokeratin fragment)	At V.aBronchial carcinoma
Skeletal alkaline phosphatase (Osteasis, bone AP)	At V.aBone metastasis 11
SCC (squamous cell carcinoma antigen)	At V.aCervical cancer
Bence-Jones proteins and Beta-2 microglobulin	At V.aPlasmacytoma
5-S-Cysteinyldopa	At V.amalignant melanoma
Neopterin, β2-microglobulin	At V.aLeukemia, lymphoma
BTA (bladder tumor antigen)	At V.aBladder cancer
M2-PK	At V.aRenal cell carcinoma, colon and rectal carcinoma
5-HIAA (5-Hydroxyindoleacetic acid)	At V.aCarcinoid (especially in the gastrointestinal tract)
Protein S100	Prognostic factor in malignant melanoma
HER2-new oncogene	Prognostic factor in breast cancer
Mutations of the BRCA1 and BRCA2 genes	Indication of breast cancer risk

Approaches to meaningful reserve diagnostics in practice (including common tumor markers)

Sample questionnaire for a "cancer check"

The u.gThis questionnaire does not replace a medical diagnosis, but rather serves to raise awareness of one's own cancer risk by asking about some relevant cancer risk factors. Even if all questions are answered in the negative, this should not be interpreted as meaning that there is no cancer risk whatsoever.

	YES
If one or more of your family members have any of the following: Cancers diagnosed: breast cancer, colon cancer, ovarian cancer, uterine cancer Stomach cancer?
Have there been periods in your life with prolonged alcohol abuse?
Have you ever had cancer in the past?
Do you have diabetes mellitus?
Have you ever had an inflammatory disease (z.B.of intestines, prostate, bladder, (Pancreas, gastric mucosa, reflux esophagitis)?
Have you had or do you have colon polyps?
Have you had or do you currently have ovarian cysts (valid for women only)?
Are you childless (valid only for women)?
Did or do you or your mother have elevated estrogen levels (only valid for men)?
Did you or do you have any birthmarks?
Have you had or do you currently have cold thyroid nodules?
Have you had or do you have an iron overload disorder?
Do you have cystic kidney disease?
Did you have a low birth weight?
Have you had or do you currently have undescended testicles?
Would you say that your oral hygiene is inadequate?
Is your diet rather unbalanced, heavy on meat, and low in fiber?
Do you drink more than 1 liter of milk per day?
Have you had or do you currently have any unusual infectious diseases?z.BSexually transmitted diseases, HPV, Epstein-Barr, HTLV, AIDS, Hepatitis, molds, Helicobacter pylori)
Do you have a known weakened immune system or immunosuppression?
Is the person childless (valid only for women)?
Have you taken or are you currently taking any medications for an extended period of time, such as... Calcium channel blockers, contraceptives, estrogens, tamoxifen, phenacetin, painkillers, Cyclophosphamide, arsenic, cytostatics, immunosuppressants or so-called aromatase inhibitors?
Did you experience your menarche rather early (only valid for women)?
If you have already gone through menopause: did it start late (only valid for women)?
Do you smoke, or have you smoked regularly for an extended period of time?
Have you been exposed to pollutants over a longer period of time?z.B. Asbestos, mercury, aromatic amines?
Shift work (especially night work)
Do you have frequently changing sexual partners?
Have you or have you been exposed to increased radiation levels?z.B.through UV light, occupation, diagnostic or therapeutic medicine)?
Do you live – or have you lived – within a 5 km radius of a Nuclear power plant?
Are you overweight?

If you answered "yes" to one or more of these questions, it is likely that you have an increased risk of cancer. In this case, be sure to discuss with your doctor what further steps should be taken.

Important micronutrient groups for general cancer prevention

micronutrient	Special features (general effects)
Antioxidants (z.B(Vit. C, Vit. E, Glutathione)	They have an antioxidant effect (protect cells from damage caused by free radicals), support detoxification, reduce overall cancer risk
Polyphenols (z.B. Isoflavonoids) Carotenoids (z.B. β-Carotene, Lycopene)	They have antioxidant and anti-inflammatory effects, support detoxification, reduce overall cancer risk
zinc	Balances the immune system, activates lymphocytes, controls apoptosis, Zinc deficiency increases cancer incidence
selenium	activates DNA repair enzymes, induces tumor cell apoptosis, reduces overall cancer risk
Magnesium, Calcium	Deficiency increases cancer incidence
iron	Deficiency increases cancer incidence
Folic acid, vitamin B6	Deficiency increases cancer risk (especially in women) &(65 years)
Vitamin B12	Caution: differing statements regarding cancer protection or cancer promotion. through B12, but: deficiency increases cancer incidence
Fatty acids (z.B.γ-Linolenic acid, Omega-3 fatty acids)	Lower overall cancer risk
Vitamin D	Lowers overall cancer risk
Vitamin K2	Lowers overall cancer risk

Key micronutrients for the Primary prevention of cancer and its special features

micronutrient	Special features
Vitamin C Standard substance	Antioxidant, cytotoxic, anti-inflammatory, anti-angiogenic, cofactor of detoxification phase I, promotes collagen formation Caution: Maintain distance from inorganic selenium and, in late-stage therapy, distance from radical-forming cytostatics and radiation.
Vitamin E (most effective as natural vitamin E (with all tocopherols)	Antioxidant, anti-inflammatory, has independent anti-cancer activity and inhibits – probably only in high pharmacological doses – the growth and mitosis of cancer cells.
Glutathion	Antioxidant, detoxifying, strengthens repair and apoptosis mechanisms, reduces cancer cell and tumor growth, improves tolerability of basic therapy without damaging healthy cells. In late-stage therapy, possibly a tumor cell protection factor (protection against therapeutic agents). radicals) and possibly multi-drug resistance (if levels increase)
α-Lipoic acid	Antioxidant, detoxifying (chelating agent)
Secondary plant compounds (Polyphenols, carotenoids)	Antioxidant, anti-inflammatory, antiproliferative, Caution: High-dose phytoestrogens in recurrent breast cancer (Conventional contraindications during hormone therapy)
Selenium (inorganic) Standard substance	reduces resistance and angiogenesis Caveat: Distance to Vitamin C
iron	Iron deficiency is common in cancer patients and must be treated optimally.
zinc	Immune-balancing, may inhibit tumor cell apoptosis (Administered after basic therapy and in case of deficiency)
B vitamins	Vitamin B12 supplementation may only be given after basic therapy and in cases of deficiency, and in combination with vitamin C (high-dose vitamin B12 may enhance [the effect]).Tumor cell growth), Other B vitamins are unproblematic.
Vitamin D	Anti-inflammatory, inhibits cell proliferation and angiogenesis, promotes apoptosis and cell differentiation, reduces tumor growth and metastasis
Vitamin A	Antioxidant, promotes cell differentiation, reduces tumor cell transformation
Proteases	Anti-inflammatory, immunotherapy, anti-cancer
Omega 3 fatty acids	Anti-inflammatory
Probiotics	Immunotherapy

Key substances in the Early cancer therapy and late cancer therapy

&

micronutrient	Study results on the effects of individual micronutrients on certain types of cancer
Antioxidants (z.B(Vit. C, Glutathione)	Prostate, breast, uterus, ovaries, intestine, lungs, pancreas, glioblastomas, melanoma
Polyphenols (z.B. resveratrol, isoflavonoids), Carotenoids (z.B. Lycopene)	Breast, ovaries, prostate, gastrointestinal tract, leukemia, pancreas, liver
selenium	Melanoma, thyroid, non-Hodgkin lymphoma, bladder, gastrointestinal tract, esophagus, leukemias, prostate, liver, lungs, breast
zinc	Acute lymphocytic leukemia (ALL), malignant lymphoma, pancreas, bladder
Calcium	Colon
magnesium	Acute lymphocytic leukemia (ALL), malignant lymphoma
Omega-3 fatty acids	Prostate, pancreas
Vitamin D	Breast, intestine, M.Hodgkin's lymphoma, melanoma, thyroid, bladder, pancreas B-CLL, myelomas
Vitamin A	bubble

Leading substances in cancer therapy and a proven Impact on certain types of cancer

Effect	substance
Cytotoxic activity	Vitamin C (increases cytotoxicity in general, especially of doxorubicin, cisplatin, docetaxel, paclitaxel, dacarbazine, epirubicin, irinotecan, 5-FU, bleomycin, carboplastin and gemcitabine, and in hematological diseases, that of arsenic trioxide) Selenium (increases cytotoxicity of Taxol, Doxorubicin, does not reduce) Cytotoxicity of radiation on cancer cells) Quercetin (increases the cytotoxicity of cisplatin, busulfan) β-Carotene (increases cytotoxicity of 5-FU, Adriamycin, Etoposide, Melphalan, Cyclophosphamide) γ-Linolenic acid and oleic acid (enhance the cytotoxic effect of docetaxel, Paclitaxel Vitamin E (enhances the cytotoxic effect of cisplatin)
Apoptosis	Selenium, α-Tocopherol, Resveratrol
Angiogenesis inhibition	Selenium, α-Tocopherol, Resveratrol, Coenzyme Q10 (with Tamoxifen)
Proliferation inhibition	Antioxidants, genistein, quercetin, vitamin D
Anti-inflammatory	Omega-3 fatty acids
Increased response rate and extension of the Survival time	Vitamin C, vitamin E and β-carotene (with paclitaxel, carboplatin), antioxidants (general), omega-3 fatty acids
Reinforcement of Tamoxifen effect	Genistein (for re-neg breast cancer), Vit D, γ-linolenic acid, coenzyme Q10, Vit B2 and Vit B3
Increase in the number of Therapy cycles	Glutathion
Improvement of Operational success (z.BImprovement of Wound healing, reduction of infection risk and Organ failure	Antioxidants (such as vitamin C, vitamin E, glutathione) selenium zinc L-Arginine, L-Glutamine Omega-3 fatty acids Probiotics
Improvement of radiation treatment success	Resveratrol, proteases, selenium

Synergistic effects of micronutrients on the university-based basic therapy

The benefits of o.gThe effects of micronutrients can be explained by their biochemical properties and by a multitude of positive study results:

• Substances that act as antioxidants and detoxifiers:

The various synergistically complementary antioxidants fulfill important functions in the primary prevention of cancer by detoxifying harmful radicals and other pollutants, and make a significant contribution to preventing their fatal carcinogenic effects.Antioxidants that can be used effectively here include vitamin C, vitamin E, vitamin A, glutathione, α-lipoic acid, coenzyme Q10 and secondary plant compounds (polyphenols, carotenoids) as well as cofactors of enzymatic antioxidants such as selenium, manganese, zinc or iron.

• Anti-inflammatory and immunomodulating substances:
  Omega-3 fatty acids and vitamin D, as well as zinc, selenium, and phytochemicals, have proven particularly effective in this function. Vitamin D z.BIn addition to its anti-inflammatory functions, it also performs important functions for a balanced immune system (acting as a regulator in the immune system, activating macrophages and the formation of endogenous antibiotics) and for calcium metabolism.
• In addition to these substances, others are also found in the o.gThe table describes substances that are directly or indirectly involved in optimizing metabolism, energy balance, and repair mechanisms – such as… Resveratrol:

Resveratrol

Using the example of the secondary plant compound resveratrol, some mechanisms of action of micronutrients for prevention (and potentially unavoidable later tumor therapy) will be described in more detail: Secondary plant compounds such as resveratrol are active in all three phases of cancer initiation and development and are suitable for broad use as chemopreventive substances against cancer initiation, but also against cancer promotion and cancer progression, which is why they can also be used complementarily in the basic treatment of the disease.

Resveratrol initially has an effect primary prevention It acts as a potent antioxidant and anti-inflammatory agent and positively influences mitochondrial function and transcription factors. blocks the activation of carcinogens and influences cancer initiation (Phase I). Through its antioxidant effects and the promotion of the formation of antioxidant enzymes (z.BCatalase, superoxide dismutase, and heme oxygenase-1 protect DNA from oxidative damage. In connection with its anti-inflammatory effects, it alters gene expression and signal transduction pathways. z.B...by inhibiting transcription factors such as EGR-1, AP-1, and NF-κB, including reducing the phosphorylation and degradation of the NF-κB inhibitor IκBα. It also likely prevents the activation of the aryl hydrocarbon receptor (AhR), which controls cell differentiation and growth.

Resveratrol influences numerous other transcription factors, including multidrug resistance protein, topoisomerase II, aromatase, DNA polymerase, estrogen receptors, tubulin, and flATPase, as well as NF-κB, STAT3, HIF-1α, β-catenin, and PPAR-γ. It blocks the transcription of the CYP1A1 gene and reacts with the enzymes CYP1A1 and CYP1B1 (from the cytochrome P450 family) produced by mutated cells. These enzymes can be pro-carcinogenic and induce therapy resistance because they inactivate chemotherapeutic agents such as tamoxifen or docetaxel. The reaction of resveratrol with CYP1B1 also produces the resveratrol metabolite and tyrosine kinase inhibitor piceatannol, which activates apoptosis in tumor cells. Hypoxia-inducible transcription factor-1α (HIF-1α) is overexpressed in many human tumors and their metastases and is closely associated with an aggressive tumor phenotype. Resveratrol inhibits both the basal levels and the accumulation of the HIF-1α protein in cancer cells.In cancer, it reduces the activity of the hypoxia-induced VEGF promoter and the release of VEGF, as well as the activity of various protein kinases, which also leads to a significant decrease in the accumulation of the HIF-1α protein and the activation of VEGF transcription.

Resveratrol also significantly inhibits the invasiveness of cancer cells. In its role in detoxification processes, it inhibits phase 1 enzymes that can activate procarcinogens and promotes the production of phase II enzymes that contribute to the detoxification of carcinogens. This improves DNA stability, influences cell differentiation and transformation, and, in mouse cancer models, prevents the development of preneoplastic lesions and tumorigenesis.

Resveratrol has an effect in the Secondary prevention or early therapy It targets various factors involved in tumor promotion and progression, thereby inhibiting tumor cell count, tumor growth, and tumor spread. Here, too, it initially downregulates via several pathways. Inflammatory processes It is involved in the synthesis and release of pro-inflammatory and cancer-promoting substances such as TNF, COX-2, ornithine decarboxylase (a key enzyme in polyamine biosynthesis), 5-LOX, VEGF, IL-1, IL-6, IL-8, AR, PSA, iNOS, and CRP. It blocks activated immune cells as well as nuclear factor B (NF-B) and AP-1, and it blocks AP-1-mediated gene expression.

Further Resveratrol inhibits the division and growth of tumor cellsIt induces cell cycle arrest in the S, G, or M phase. It modulates cell cycle regulatory genes such as p53, Rb, PTEN, cyclin A, cyclin B1, cyclin E, Stat3-regulated cyclin D1, and CDK, and simultaneously induces p53-independent and p21-expression-mediated cell cycle inhibition.

Resveratrol suppresses angiogenesis, which is important for tumor growth by reducing the expression of VEGF and other angiogenic and pro-metastatic gene products (z.B. MMPs, Cathepsin D and ICAM-1). It inhibits DNA synthesis by blocking ribonucleotide reductase or DNA polymerase and by altering biomarker expression.

Resveratrol promotes pro-apoptotic factors and induces the process essential for protection against cancer. programmed cell death (see figure), in which two main forms can be distinguished: the “lethal” autophagy (programmed cell death type II) and apoptosis (programmed cell death type I).

Factors influencing programmed cell death in cancer

The Apoptosis is the more well-known form of programmed cell death and can be initiated both extrinsically and intrinsically.

• The extrinsic pathway begins with the binding of a ligand (z.BTNF o.a. cytokines) to a receptor of the TNF receptor family (z.B. CD95), which triggers the caspase cascade and leads to apoptosis.
• In the intrinsic pathway, DNA damage activates tumor suppressors such as p53. P53 stimulates substances of the pro-apoptotic Bcl-2 family (Bax, Bad), which release cytochrome c from mitochondria, thereby triggering the caspase cascade and the final apoptosis.

Apoptosis can be suppressed by anti-apoptotic substances of the Bcl-2 family (Bcl-2, Bcl-xL) as well as by protein kinase B and IAP (inhibitor of the apoptosis protein). Resveratrol induces programmed cell death through the expression of pro-apoptotic proteins. Bax, p53 and p21 as well as through depolarization of mitochondrial membranes and CD95-independent activation of caspases (z.B. Caspase-9, Caspase-3).

Resveratrol also inhibits anti-apoptotic effects. It inhibits various protein kinases in cancer cells, such as IκBα kinase, src, JN kinase, MAP kinase, protein kinase B, protein kinase D, as well as COX-2 mRNA- and TPA-induced protein kinase C and casein kinase 2. It suppresses the expression of anti-apoptotic genes and gene products such as Clap-2, Bcl-2, Bcl-xL, and XIAP. It blocks the release of survivin by inhibiting the mRNA for survivin and activating sirtuin deacetylase. Survivin is produced by cancer cells and is among the inhibitors of apoptosis proteins released in most human cancers. It can inhibit mitochondrial-dependent apoptosis and facilitate aberrant mitotic progression by inactivating the cell death protease caspase-9.

Resveratrol can also supportive in late-stage cancer therapy can be used. It It sensitizes tumor cells to other therapies and exhibits its own cytotoxic activity.It can synergistically improve the effects of chemotherapy and radiation therapy and can reduce both side effects and resistance to chemotherapeutic agents.

Besides resveratrol, many other secondary plant compounds are also involved in production. similar effect described how z.B. for the Epigallocatechin-3-gallate (EGCG) in green tea, which blocks an important enzyme involved in the proliferation of cancer cells.Among the lesser-known secondary plant compounds are the protease inhibitors, which are found primarily in soybeans, legumes, and various grains. They are also said to have a good anti-cancer effect, as evidenced by the fact that synthetic protease inhibitors such as bortezomib are now used in university oncology. The approach that resveratrol interacts with other secondary plant compounds (z.B. Quercetin) has a positive synergistic effect and that no significant cytotoxicity towards healthy cells is found in any of the processes influenced by resveratrol.

Selected studies on resveratrol in oncology

• Resveratrol Resveratrol acts as a cancer chemopreventive agent. Here, we discovered a new function of resveratrol: Resveratrol is a potent sensitizer of tumor cells for tumor necrosis factor-dependent, apoptosis-inducing ligand (TRAIL)-induced apoptosis through p53-independent induction of p21 and p21-mediated inhibition of the cell cycle, associated with survivin depletion. Simultaneous analysis of cell cycle, survivin expression, and apoptosis showed that resveratrol-induced G(1) inhibition was associated with a downregulation of survivin expression and sensitization to TRAIL-induced apoptosis. Accordingly, G(1) inhibition by the cell cycle inhibitor mimosin or by p21 overexpression reduced survivin expression and sensitized cells to TRAIL treatment. Resveratrol-mediated cell cycle inhibition with subsequent survivin depletion and sensitization to TRAIL was impaired in p21-deficient cells. Downregulation of survivin with survivin antisense oligonucleotides also sensitized the cells to TRAIL-induced apoptosis.Importantly, resveratrol sensitizes various tumor cell lines, but not normal human fibroblasts, to apoptosis induced by dead receptor ligation or cancer drugs. This combined sensitizer (resveratrol) and inducer (e.g., TRAIL) strategy could represent a novel approach to improving the efficacy of TRAIL-based therapies.
  These therapies can be used for a wide variety of cancers.
  (Fulda S, Debatin KM; Sensitization for tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by the chemopreventive agent resveratrol; Cancer Res 2004; 64; 337-346)
• Resveratrol Resveratrol is a chemopreventive agent against cancer. It has been shown to have antioxidant and antimutagenic effects, thus acting as an anti-induction agent. Resveratrol selectively suppresses the activation of cytochrome P-450 1A1 transcription and inhibits the formation of carcinogen-induced preneoplastic lesions in mouse models. It also inhibits the formation of 12-OTetradecanoylphorbol-13-acetate (TPA)-promoted skin tumors in a two-phase model. The enzymatic activity of COX-1 and -2 is inhibited in cell-free models, and COX-2 mRNA- and TPA-induced activation of protein kinase C and AP-1-mediated gene expression are suppressed by resveratrol in mammary epithelial cells. Furthermore, resveratrol strongly inhibits nitric oxide generation and the expression of the iNOS protein. NFκB is closely associated with inflammatory and immune responses, as well as with oncogenesis in some cancer models. Resveratrol suppresses the induction of this transcription factor. The mechanism also involves a reduction in phosphorylation and degradation of NFκBα. At the cellular level, resveratrol induces apoptosis, cell cycle retardation, or blockage of the G1→S transition phase in a number of cell lines.
  (Bhat K, Pezzuto JM; Cancer Chemopreventive Activity of Resveratrol, Annals of the New York Academy of Sciences 2006; 957; 210-229)
• Resveratrol It combats inflammation and disease by modulating many different pathways. It binds to numerous cell signaling molecules such as multi-drug resistance protein, topoisomerase II, aromatase, DNA polymerase, estrogen receptors, tubulin, and Fl-ATPase. It activates various transcription factors (e.g., NF-κB, STAT3, HIF-1α, β-catenin, and PPAR-γ) and suppresses the expression of anti-apoptotic gene products (z.B. Bcl-2, Bcl-XL, XIAP and Survivin) and protein kinases (z.B. src, PI3K, JNK and AKT), induces antioxidant enzymes (z.BCatalase, superoxide dismutase, and heme oxygenase-1 suppress the expression of inflammatory biomarkers (z.B. TNF, COX-2, iNOS and CRP), inhibits the expression of angiogenic and metastatic gene products (z.B. MMPs, VEGF, Cathepsin D and ICAM-1) and modulates cell cycle regulatory genes (z.Bp53, Rb, PTEN, Cycline, and CDK). Numerous animal studies have shown that resveratrol is effective against numerous age-related diseases, including cancer, diabetes, Alzheimer's disease, cardiovascular disease, and lung disease. Efforts are also underway to enhance its efficacy in vivo through structural modification and reformulation.
  (Harikumar KB et al.; Resveratrol: a multitargeted agent for age-associated chronic diseases; Cell Cycle 2008; 7; 1020-1035)
• Compelling evidence demonstrates the positive effects of Resveratrol It affects the nervous system, liver, cardiovascular system, and cancer chemoprevention. It blocks the various phases of cancer development (tumor initiation, promotion, and progression).One of the possible mechanisms for its biological activities involves the downregulation of inflammatory responses by inhibiting the synthesis and release of pro-inflammatory mediators, altering eicosanoid synthesis, and inhibiting activated immune cells of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) via its inhibitory effect on nuclear factor B (NF-κB) or activator protein-1 (AP-1). Recent data offer interesting insights into the effects of resveratrol on the lifespan of yeast and flies, highlighting its potential as an anti-aging agent in the treatment of age-related diseases in humans. It should be noted, however, that resveratrol has low bioavailability and rapid clearance from plasma. This article considers its strong anti-inflammatory activity and the plausibility of these mechanisms, and provides an update on the bioavailability and pharmacokinetics of resveratrol as well as its effects on lifespan.
  (De la Lastra CA, Villegas I; Resveratrol as an anti-inflammatory and anti-aging agent: mechanism and clinical implications; Molecular Nutrition and Food Research 2005; 49; 405-430)
• Resveratrol It inhibits growth, S-phase cell cycle arrest, and changes in biomarker expression in human cancer cell lines. It differentially reduces the expression of cyclin B1, cyclin A, cyclin D1, and beta-catenin. It induces apoptosis.
  (Joe AK et al.; Resveratrol induces growth inhibition, S-phase arrest, apoptosis, and changes in biomarker expression in several human cancer cell lines. Cancer Res. 2002; 8, 893-903)
• Resveratrol It inhibits the growth of leukemia cells in cultures. It induces leukemia cell differentiation, apoptosis, cell cycle arrest in the S phase, and inhibition of DNA synthesis by blocking ribonucleotide reductase or DNA polymerase.
  (Tsan MF et al.; Anti-leukemia effect of resveratrol. Leuk. Lymphoma 2002; 43, 983-987)
• Resveratrol It reduces the growth of human colon cancer cells by 70%. The cells
  accumulated during the S/G2 phase transition of the cell cycle. Resveratrol significantly reduces the activity of ornithine decarboxylase (a key enzyme in polyamine biosynthesis, which is involved in cancer growth).
  (Schneider Y et al.; Anti-proliferative effect of resveratrol, a natural component of grapes and wine, on human colonic cancer cells. Cancer Lett. 2000; 158, 85-91)
• Resveratrol In rapidly growing rat tumors, it significantly reduces tumor growth and leads to an increase in the number of cells in the G2/M cell cycle phase. It induces apoptosis and leads to a decrease in cell count.
  (Carbo N et al; Resveratrol, a natural product present in wine, decreases tumor growth in a rat tumor model. Biophys. Res. Commun. 1999; 254, 739-743)
• Resveratrol It induces apoptosis in more than 80% of CD95-sensitive and CD95-resistant cells of acute lymphoblastic leukemia (ALL) through depolarization of mitochondrial membranes and activation of caspase-9, independent of CD95 signaling. No significant cytotoxicity to normal peripheral blood cells is observed.
  (Dorrie J et al.; Resveratrol induces extensive apoptosis by depolarizing mitochondrial membranes and activating caspase-9 in acute lymphoblastic leukemia cells. Cancer Res. 2001; 61, 4731-4739)
• Resveratrol (200 mcg/kg) significantly reduces colon cancer carcinogenesis in rats.It significantly reduces the cell count and alters the expression of bax and p21.
  (Tessitore L et al.; Resveratrol depresses the growth of colorectal aberrant crypt foci by affecting bax and p21 (CIP) expression. Carcinogenesis 2000; 21, 1619-1622)
• Resveratrol Resveratrol develops antiproliferative activity. It inhibits proliferation and induces cytotoxicity and apoptosis in Waldenström's macroglobulinemia (WM) cells. Peripheral blood cells are not affected. Resveratrol exhibits synergistic cytotoxicity when combined with dexamethasone, fludarabine, and bortzomib.
  (Roccaro AM et al.; Resveratrol Exerts Antiproliferative Activity and Induces Apoptosis in Waldenstrom's Macroglobulinemia; Clin. Cancer Res 2008; 14: 1849 – 1858)
• Resveratrol Resveratrol acts on all three stages of carcinogenesis (initiation, promotion, and progression) by altering signal transduction pathways that control cell division, cell growth, apoptosis, inflammation, angiogenesis, and metastasis. The anti-cancer properties of resveratrol are supported by its ability to inhibit the proliferation of a variety of human tumor cells in vitro and in animal studies. This review presents data from preclinical in vivo and interventional studies on cancer and the associated mechanisms of action. Furthermore, the bioavailability, pharmacokinetics, and potential toxicity of resveratrol, as well as its usefulness in cancer, are discussed.
  (Bishayee A; Cancer prevention and treatment with resveratrol: from rodent studies to clinical trials; Cancer Prev Res (Phila Pa) 2009; 2: 409-418)
• Resveratrol significantly inhibits in pancreatic carcinoma cell lines (PANC-1 and AsPC-1) the
  Cell growth is concentration- and time-dependent and induces cell apoptosis.
  (Ding XZ et al.; Resveratrol inhibits proliferation and induces apoptosis in human pancreatic cancer cells; Pancreas 2002; 25: e71-76)
• Resveratrol Resveratrol exhibits anticancer properties and suppresses the proliferation of a variety of tumor cells. Its growth-inhibiting effect is mediated by cell cycle inhibition with upregulation of p21 (CIP1/WAF1), p53, and Bax, as well as downregulation of survivin, cyclin D1, cyclin E, Bcl-2, Bcl-xL, and clAPs, and activation of caspases. Resveratrol suppresses the activation of transcription factors such as NF-κB, AP-1, and EGR-1, and inhibits protein kinases, including IkBα kinase, JNK, MAPK, Akt, PKC, PKD, and casein kinase II. It downregulates COX-2, 5-LOX, VEGF, IL-1, IL-6, IL-8, AR, and PSA. These activities are responsible for the suppression of angiogenesis. Resveratrol also enhances the apoptotic effects of cytokines, chemotherapeutic agents, and radiation. It blocks carcinogen activation by inhibiting the expression and activity of CYP1A1 and suppresses the initiation, promotion, and growth of tumors. In addition to its chemopreventive effects, resveratrol appears to have therapeutic effects against cancer.
  (Aggarwal BB et al.; Role of Resveratrol in prevention and therapy of cancer: preclinical and clinical studies; Anti-cancer Res 2004; 24; 2783-2840)
• Resveratrol In addition to its protective function on the cardiovascular system, resveratrol influences all three stages of cancer development (tumor initiation, promotion, and progression). It also suppresses angiogenesis and metastasis. The anti-cancer effects of resveratrol appear to be closely linked to its ability to interact with multiple molecular parameters involved in cancer development, while minimizing toxicity in healthy tissue.Resveratrol should therefore be used in human cancer chemoprevention in combination with chemotherapeutic agents or cytotoxic factors for the highly effective treatment of drug-refractory tumor cells. The anti-carcinogenic potential of resveratrol for cancer chemoprevention and anti-cancer therapy represents, in a sense, a new explanation of the French Paradox.
  (Liu BL et al.; New enlightenment of French Paradox: resveratrol's potential for cancer chemoprevention and anti-cancer therapy; Cancer Biol Ther 2007; 6: 1833-1836)
• Several studies have demonstrated the modulating effect of Resveratrol Resveratrol has been shown to act on a variety of cell signaling pathways and gene expression. This article summarizes the effects of resveratrol in the context of chemoprevention.
  (Goswami SK, Das DK; Resveratrol and chemoprevention; Cancer Lett 2009; 284: 1-6)
• Resveratrol Resveratrol possesses a strong growth-inhibiting effect against various human cancer cells. Here, the inhibitory effect of resveratrol on experimental liver cancer is investigated using a two-stage rat model. Resveratrol (50-300 mg/kg body weight) reduces the incidence, number, volume, and diversity of visible hepatocyte nodules in a dose-dependent manner. It leads to a decrease in cell proliferation and an increase in apoptotic cells in the liver. It also induces the expression of the pro-apoptotic protein Bax, reduces the expression of the anti-apoptotic protein Bcl-2, and simultaneously increases the Bax/Bcl-2 ratio. Due to its favorable toxicity profile, resveratrol has the potential to be developed as a chemopreventive drug against human hepatocellular carcinoma.
  (Bishayee A, Dhir N; Resveratrol-mediated chemoprevention of diethylnitrosamine-initiated hepatocarcinogenesis: inhibition of cell proliferation and induction of apoptosis; Chem Biol Interact 2009; 179: 131-44)
• The aim of this study was to Interactions of ellagic acid and quercetin with resveratrol (Polyphenols) have been shown to induce apoptosis and reduce cell growth in human leukemia cells (MOLT-4). The combination of ellagic acid and resveratrol exhibits more than additive synergistic effects. Both substances, individually and together, induce significant changes in cell cycle kinetics. Positive synergistic interactions exist between ellagic acid and resveratrol, as well as between quercetin and resveratrol, in the induction of caspase-3 activity. The anticancer potential of foods containing polyphenols can be enhanced through synergistic effects.
  (Mertens-Talcott SU, Percival SS; Ellagic acid and quercetin interact synergistically with resveratrol in the induction of apoptosis and cause translent cell cycle arrest in human lekemia cells; Cancer Lett 2005; 218; 141-151)
• Resveratrol HCT116 has a cancer-preventive effect and, at physiological doses, induces Bax-mediated and Bax-independent mitochondrial apoptosis in human colon carcinoma cells. Both pathways limit the cells' ability to form colonies.
  (Mahyar-Roemer M et al.; Role of Bax in resveratrol-induced apoptosis of colorectal carcinoma cells; BMC Cancer 2002; 2; 27-36)
• Intervening in multi-stage carcinogenesis by modulating intracellular signaling pathways can provide a molecular basis for chemoprevention with secondary plant metabolites. Resveratrol It was extensively investigated for its chemopreventive activity in relation to its ability to intervene in multi-stage carcinogenesis.Numerous intracellular signaling cascades converge with the activation of nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1), which act independently or in coordination to regulate the expression of target genes. These ubiquitous eukaryotic transcription factors mediate pleiotropic effects on cellular transformation and tumor promotion. The aim of this review is to update the molecular mechanisms of resveratrol's chemoprevention, with particular attention to its effects on NF-kappaB- and AP-1-mediated cellular signaling cascades. Resveratrol It significantly downregulates Survivin and the cell cycle in a dose- and time-dependent manner, induces apoptosis, and improves the effect of chemotherapeutic agents in multidrug-resistant non-small cell lung cancer cells.
  (Zhao W et al.; Resveratrol down-regulates survival and induces apoptosis in human multidrug-resistant SPC-A-1/CDDP cells; Oncology Reports 2010; 23; 279-286)
• Resveratrol It has antineoplastic activity. It inhibits the growth and induces the death of ovarian carcinoma cells (more via autophagy than via apoptosis). u.a...associated with caspase activation. It therefore induces cell death via two different pathways: non-apoptotic and apoptotic (via release of the anti-apoptotic proteins Bcl-xL and Bcl-2).
  (Opipari AW et al.; Resveratrol-induced autophagocytosis in ovarian cancer cells; Cancer Research 2004; 64, 696-703)
• Resveratrol Resveratrol inhibits Src tyrosine kinase activity, thereby blocking the activation of the constitutive signaling and transcription activator 3 (Stat3) protein in malignant cells. Analyses of resveratrol-treated malignant cells containing constitutively active Stat3 show irreversible cell cycle arrest in v-Src-transformed mouse fibroblasts (NIH3T3/v-Src), human breast (MDAMB-231), pancreatic (Panc-1), and prostate cancer (DU145) cell lines in the G0-G1 or S phase of human breast cancer (MDA-MB-468) and pancreatic cancer (Colo-357) cells, and loss of viability due to apoptosis. In contrast, cells treated with resveratrol but lacking aberrant Stat3 activity exhibit reversible growth arrest and minimal loss of viability. Furthermore, in malignant cells containing constitutively active Stat3, including human prostate cancer DU145 cells and v-Src transformed mouse fibroblasts (NIH3T3/v-Src), resveratrol suppresses Stat3-regulated cyclin D1, as well as the Bcl-xL and Mcl-1 genes, suggesting that resveratrol's anti-tumor cell activity is partly due to the blockade of Stat3-mediated dysregulation of growth and survival pathways. Our study is among the first to identify Src-Stat3 signaling as a target of resveratrol, define the mechanism of resveratrol's anti-tumor cell activity, and demonstrate its potential for application in tumors with an activated Stat3 profile.
  (Kotha A et al.; Resveratrol inhibits Src and Stat3 signaling and induces the apoptosis of malignant cells containing activated Stat3 protein; Mol. Cancer Ther 2006; 5: 621 – 629)
• Hypoxia-inducible factor-1α (HIF-1α) is overexpressed in many human tumors and their metastases and is closely associated with an aggressive tumor phenotype. In this study, we investigated the effect of Resveratrol on the accumulation of the hypoxia-induced HIF-1α protein and the expression of the vascular endothelial growth factor (VEGF) in squamous cell carcinomas of the tongue and in hepatoma cells.Resveratrol significantly inhibits both basal levels and accumulation of hypoxia-induced HIF-1α protein in cancer cells, but not HIF-1α mRNA levels. Pretreatment of cells with resveratrol significantly reduced the activity of the hypoxia-induced VEGF promoter and VEGF secretion at both the mRNA and protein levels. The mechanism by which resveratrol inhibits the accumulation of hypoxia-induced HIF-1α appears to involve a shortened half-life of the HIF-1α protein, caused by increased protein degradation by the 26S proteasome system. Furthermore, resveratrol inhibits the hypoxia-mediated activation of the extracellular signal-regulated kinases 1/2 and Akt, leading to a significant decrease in the accumulation of hypoxia-induced HIF-1α protein and the activation of VEGF transcription. Resveratrol also significantly inhibits hypoxia-stimulated cancer cell invasiveness. These data suggest that HIF-1α/VEGF could represent a promising target for resveratrol in the development of effective chemoprevention and therapy against human cancers.
  (Zhang Q et al.; Resveratrol inhibits hypoxia-induced accumulation of hypoxia-inducible factor-1{alpha} and VEGF expression in human tongue squamous cell carcinoma and hepatoma cells; Mol. Cancer Ther 2005; 4: 1465 – 1474)
• Many recent studies have shown promising health benefits of red wine. This article provides an overview of some of the most important studies and the mechanisms behind these positive effects. It has been shown that these positive effects are due to polyphenols in red wine, especially... Resveratrol These effects are attributed to the polyphenols found in grape skins. They include a reduction in cardiovascular morbidity and mortality, lung cancer, and prostate cancer by approximately 30% to 50%, 57%, and 50%, respectively. Polyphenols possess antioxidant, superoxide scavenging, ischemia-preconditioning, and angiogenic properties. Some of these properties of polyphenols may explain their protective effects on the cardiovascular system and other organs of the body. Therefore, the United States Department of Health and Human Services, in its national health promotion and prevention initiative "Healthy People 2010," recommended moderate alcohol consumption.
  (Review; Vidavalur R et al.; Significance of wine and resveratrol in cardiovascular disease: French paradox revisited; Exp Clin Cardiol. 2006; 11: 217–225)

Vitamin C

Vitamin C plays a particularly important role in cancer therapy (see figure). Several different mechanisms of action of the substance come into play:

• The antioxidant effect, for which there is sufficient evidence for use in supportive oncology therapy. In this way, vitamin C protects healthy cells, reduces side effects, improves the effectiveness of standard therapy, and enhances quality of life.
• The cytotoxic effect on cancer cells above all with high-dose parenteral administrationIt is triggered, as with radiation and some chemotherapeutic agents, via anti-proliferative mechanisms, but especially via pro-oxidative effects mediates the formation of H2O2. With oral administration of vitamin C, a cytotoxic effect was only observed in the context of early therapy, where it z.BIt can also reduce the levels of tumor markers, but not in late-stage therapy. (z.B. Creagan, Moertel et al.; 1979).This can be explained by the fact that when taken orally, the amounts of vitamin C absorbed are too low to achieve sufficiently high plasma levels over a longer period in already visible tumors to exert a cytotoxic effect in the form of apoptosis and autophagy. In contrast, there is sufficient evidence that parenteral administration of vitamin C at pharmacological doses in late-stage therapy achieves sufficient therapeutic levels from approximately 25-30 mmol/l and is particularly useful in combination with other agents, taking into account potential interactions with chemotherapeutic agents and radiation, in first-line chemotherapy for a wide variety of tumor types – without the risk of systemic toxicity or damage to healthy cells.
• Furthermore, vitamin C has anti-inflammatory properties, activates collagen production, increases the cytotoxic potency of chemotherapeutic agents, reduces side effects such as pain, fatigue, vomiting or loss of appetite, and contributes to improving the quality of life of tumor patients.

Antioxidant and pro-oxidative effects of vitamin C in oncology

selenium

Similar to vitamin C, selenium also plays a key role in the early and late treatment of malignant tumors.

• It has antineoplastic and tumor-selective cytotoxic effects, inhibits tumor growth, invasion and angiogenesis, and improves the detectability of tumor tissue.
• It promotes apoptosis of irreparable cells (z.B. via activation of p53, p21, BAX and cytochrome C)
• It increases the expression of selenium-dependent enzymatic antioxidants.
• It activates NK cells and potentiates the antitumor cytotoxicity of NK cell-based immunotherapies.
• It protects healthy cells and reduces side effects of the basic therapy without loss of effectiveness.
• It has a prophylactic effect against lymphedema and erysipelas.
• It reduces the risk of resistance and resensitizes resistant tumor cells to therapy.
• It reduces the risk of metastases and recurrence, as well as mortality.
• Selenium deficiency reduces the chances of success of basic university therapy; good selenium intake and additional selenium supplementation increase them.

Selected studies on selenium in oncology

• CD94/NKG2A controls the activity of NK cells. Selenite It reduces the expression of HLA-E on tumor cells and can potentiate the antitumor cytotoxicity of NK cell-based immunotherapies.
  (Enquist M et al.; Selenite induces posttranscriptional blockade of HLA-E expression and sensitizes tumor cells to CD94/NKG2A-positive N cells; J Immunol 2011; 187; 3546-3554)
• Selenite It oxidizes polythiols to corresponding disulfides and does not react with monothiols. It makes cancer cells more vulnerable to surveillance and destruction by the immune system. It activates NK cells and inhibits angiogenesis.
  (Lipinski B; Rationale for the treatment of cancer with sodium selenite; Med Hypotheses 2005; 64; 806-810)
• Redox-active selenium It inhibits the growth of cancer cells and has tumor-selective cytotoxic effects without resistance formation.
  (Wallenberg M et al.; Selenium cytotoxoicity in Cancer; Basic && Clinical Pharmacology && Taxocology 2014; 1-10)
• Low doses of selenium promote cell growth, while high concentrations inhibit it. selenium It induces apoptosis in malignant cells and does not affect normal cells.
  (Björnstedt M, Fernandes AP; Selenium in the prevention of human cancers. EPMA J 2010;1: 389-95)
• Low seleniumConcentrations are essential for cell growth; high concentrations selectively induce cell death in tumor cells.
  (Selenius M et al.; Selenium and the selenoprotein thioredoxin reductase in the prevention, treatment and diagnosis of cancer. Antioxid Redox Signal 2010;12: 867-80)
  
  selenium It can reduce the risk of cancer as well as progression and metastasis in all types of cancer (and especially in prostate, liver, gastrointestinal and lung cancer), particularly in people with low selenium status (it comes from u.a. leading to a reduction in DNA damage and oxidative stress).
  (Rayman MP; Selenium in cancer prevention: a review of the evidence and mechanism of action; Proc Nutr Soc 2005; 64; 527-542)
• seleniumSupplementation increases antioxidant protection through increased expression of selenium-dependent GSH peroxidase and thioredoxin reductase. Selenium protects against cancer: it influences tumor metabolism, the immune system, cell cycle regulation, and apoptosis.
  (Combs GF Jr; Chemopreventive mechanism of selenium; Med Klin 199; 94 Suppl 3; 18-24)

Enzymes

In therapeutic use in cancer, three main groups of enzymes can be distinguished:

• the antioxidant enzymes (see under Antioxidants)
• the detoxifying enzymes (see under detoxification)
• the proteolytic enzymes (proteases)

Many of these enzymes require cofactors, coenzymes or cosubstrates for their activities, such as B vitamins, iron, zinc, selenium, manganese, magnesium or polyphenols, which belong to the inner circle of micronutrients.

Proteases belong to the hydrolases. In complementary oncology, the substances are primarily used. Bromelain and papain as well as trypsin and chymotrypsin, which are mostly used in combination in enteric-coated preparations.

The proteases act z.BThey are anti-inflammatory, improve phagocytosis, stimulate the body's own defenses, reduce immune and cytokine complexes as well as adhesion molecules and TGFβ, resorb edema and hematomas, and contribute to the unmasking of tumor cells. They are primarily used in late-stage cancer therapy, where they act synergistically with standard university-based therapy and improve quality of life. However, they can also be used in early-stage therapy, for the prevention of metastases, as palliative care, and in cases of malignant effusions.

Study examples and articles on the use of micronutrients in cancer treatment

PREVENTION

i) Cancer risk in general

• Chronic inflammation
  • There are different effects of Inflammatory processes It has been described in relation to cancer. Acute inflammation generally reduces the development of cancer, while chronic inflammation promotes it. During z.BWhile IL-6 inhibits apoptosis and can promote cancer development, interferons can promote DNA repair and stabilize p53. They therefore have an anti-oncogenic effect. (Philip M et al.; Inflammation as a tumor promoter in cancer induction; Semin Cancer Biol 2004; 14; 433-439)
  • Chronic Inflammation are responsible for up to 20% of all cancers, z.BInflammatory
    Intestinal diseases (M.Crohn, ulcerative colitis), viral infections, bacterial infections (z.BThese include infections such as Helicobacter pylori, parasitic infections, asbestos exposure, alcohol and nicotine abuse, and obesity. They lead to an overproduction of free radicals and lipid peroxidation. These are responsible for DNA damage, tumor cell growth, tumor spread, and the activation of cancer genes. (German Medical Journal; How chronic inflammation leads to cancer; International expert meeting at the German Cancer Research Center Heidelberg; March 10, 2006)
  • Inflammation They contribute to the development of approximately 15% of all cancers. Inflammation and the resulting
    Inflammation-induced NFkB protein contributes to uncontrolled cancer cell growth and to
    Macrophages produce substances that stimulate tumor growth, including TNF-alpha, which boosts NF-κB activity. Tumor cells produce substances such as CSF-1 (colony-stimulating factor 1) and COX-2, which in turn promote inflammation. NSAIDs reduce the risk of cancer by inhibiting inflammation. Components of red wine and green tea act as NF-κB inhibitors.
    (Marx J; Cancer research. Inflammation and cancer: the link gets stronger; Science 2004; 306; 966-968)
• Antioxidants
  • apples Apples have a high antioxidant capacity, suppress the proliferation of cancer cells, and reduce lipid oxidation and cholesterol. They contain various secondary plant compounds, including quercetin, catechin, and phloridzin. The phytochemical content varies considerably between different apples, and there are also differences in phytochemical content during the ripening process.
    (Review; Boyer J et al.; Apple phytochemicals and their health benefits; Nutr J 2004; 3; 5)
  • After 7.5 years, lower Antioxidants (Beta-carotene 6 mg, Zinc 20 mg, Selenium 100 mcg, Vitamin C 100 mg, Vitamin E 30 mg) The study significantly reduced cancer risk (relative risk 0.69, 95% CI) and overall mortality (relative risk 0.63, 95% CI) in men. Note: Results were not available for women; men had lower blood levels of antioxidants.
    (Randomized, double-blind, placebo-controlled; 13,017 participants; SU.VI.MAX; 2004; Serge Hercberg et al.; Arch Intern Med. 2004; 164; 2335-2342)
  • Overall cancer mortality is associated with low levels of Carotene and vitamin C (and retinol). Low Vitamin EElevated levels of methylphenidate (methylphenidate) are associated with an increased risk of lung cancer and, in smokers, with an increased risk of prostate cancer.
    (2974 participants over 17 years old; Eichholzer M et al.; Prediction of male cancer mortality by plasma levels of interacting vitamins; 17-year follow up of the prospective Basel Study; Int J of Can 1996; 66; 145-150; Stahelin HB et al.; Plasma antioxidant vitamins and subsequent cancer mortality in twelve-year follow-up of the prospective Basel Study. Amer J of Epidemic 1991; 133; 766-775)
  • Vitamin and mineral supplementation (especially with the combination of Beta-carotene, vitamin E and selenium) reduces the cancer risk in the population of Linxian (RR 0.91; 95% CI).
    (Randomized, 29584 participants; Blot W et al.; Nutrition intervention trials in Linxian, China: Supplementation with specific vitamin/mineral combinations, cancer incidences and disease-specific mortality in the general population. J of the Nat Can Inst; 1993; 85; 1483-1492)
  • Low Alpha tocopherol levels increase the risk of cancer by 1.5 times for various types of cancer; the correlation is strongest for gastrointestinal tumors and for cancers that are independent of nicotine abuse, as well as for non-smokers with low selenium levels.
    (36265 participants over 8 years; Knekt P et al.; Vitamin E and cancer prevention; The Amer J of Clin Nutr 1991; 53; 283S-286S)
  • The risk of malignant melanoma is reduced at the highest compared to the lowest plasma levels of β-Carotene (OR 0.9; 95% CI) and for total-Vitamin E (OR 0.7; 95% CI).
    (452 participants; Stryker WS et al.; Diet, plasma levels of beta-carotene and alpha-tocopherol, and risk of malignant melanoma; Am J Epidemiol 1990;131: 597-611)
• Resveratrol
  • Inhibition of tumor initiation by Resveratrol This effect likely occurs through the inhibition of Ah receptor activation. Resveratrol also influences several factors involved in tumor promotion and progression. Since tumor-promoting substances alter the expression of genes whose products are associated with inflammation, chemoprevention of cardiovascular disease, and cancer, common mechanisms may exist. These include, in particular, the modulation of growth factor and cytokine expression. Recently, the chemopreventive properties of resveratrol have been linked to the inhibition of NF-κB. This transcription factor is closely associated with inflammatory and immune responses, as well as with the regulation of cell proliferation and apoptosis. It is therefore important for tumorigenesis and many other diseases, such as atherosclerosis. Although the mechanisms by which resveratrol interferes with NF-κB activation are not clear, it appears that inhibiting its degradation, which is necessary for its cellular activation, is the primary target. Based on the quantity and variety of available data on the biological activity of resveratrol, it must be considered a very promising chemoprotector and chemotherapeutic agent.
    (Ignatowicz E et al.; Resveratrol, a natural chemopreventive agent against degenerative diseases; Pol J; Pharmacol 2001; 53; 557-569)
  • Resveratrol Resveratrol exhibits cancer chemopreventive activity at three key stages of cancer development. It acts as an antioxidant and antimutagenic agent and induces phase II drug-metabolizing enzymes (anti-initiation activity). It mediates anti-inflammatory effects and inhibits cyclooxygenase and hydroperoxidase functions (anti-promotion activity) and induces the differentiation of human promyelocytic leukemia cells (anti-progression activity). Furthermore, it prevents the development of preneoplastic lesions in carcinogen-treated mice and inhibits tumorigenesis in a mouse skin cancer model. These data suggest that resveratrol is a potentially suitable chemopreventive agent for use in humans.
    (Jang MS et al.; Cancer chemopreventive activity of reseveratrol, a natural product derived from grapes; Science; 1997; 275; 218-220)
  • Resveratrol It is a chemoprotective substance against skin cancer and activates sirtuin deacetylase. It extends the lifespan of lower organisms and has protective effects against stress and disease.
    (Baur JA, Sinclair DA; Therapeutic potential of resveratrol: the in vivo evidence; Nature Reviews Drug
    Discovery 2006; 5, 493-506)
• selenium
  • In patients with a history of skin cancer, selenium 200 mcg compared to placebo did not significantly reduce the incidence of basal cell carcinoma and squamous cell carcinoma (RR 1.10 and RR 1.14, respectively; 95% CI). Patients receiving selenium had a non-significant reduction in all-cause mortality (RR 0.83; 95% CI) and a significant reduction in Overall cancer mortality (RR 0.50; 95% CI) and Overall cancer incidence (RR 0.63; 95% CI).
    (Double-blind, randomized, placebo-controlled; 1312 participants over 8 years (1983-1991); Clark LC et al.; Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial.) Nutritional Prevention of Cancer Study Group; JAMA 1996; 276; 1957-1963)
• Vitamin D
  • Low Vitamin D-Levels are associated with an increased risk of Cancer incidence and mortality In men, particularly in the gastrointestinal tract. An increase in vitamin D levels of 25 nmol/l is associated with a 17% reduction in overall cancer risk and a 45% reduction in gastrointestinal cancer mortality.
    (Prospective cohort study; Health Professionals Follow-Up Study with 47800 participants over 14 years. Giovannucci E et al.; Prospective Study of Predictors of Vitamin D Status and Cancer Incidence and Mortality in Men; JNCI Journal of the National Cancer Institute 2006 98(7):451-459)
  • There is a clear connection between Vitamin D-status and the risk for colon, breast, prostate and ovarian cancer.
    (30 colon, 13 breast, 26 prostate and 7 ovarian carcinomas from 63 clinical trials; Garland CF et al.; The role of vitamin D in cancer prevention; Am J Public Health 2006; 96; 252-261)
• Calcium
  • Calcium Generally, it protects women against cancer. Doses above 1300 mg do not result in an increased risk reduction. Dairy products (z.BThree cups of low-fat or fat-free dairy products and calcium offer dose-dependent protection against gastrointestinal and, in particular, colorectal cancer in men (RR 0.84) and women (RR 0.77). Calcium intake does not correlate with the risk of breast cancer or cancers of the endometrium, ovary, and prostate.
    (Prospective National Institutes of Health-AARP Diet and Health Study (cohort study) over 7 years)
    Park Y et al.; Dairy Food, Calcium, and Risk of Cancer in the NIH-AARP Diet and Health Study; Arch Intern Med 2009; 169; 391-401)
  • The CalciumCalcium intake is associated with overall cancer risk in women and decreases up to a calcium intake of 1300 mg/day. Higher doses do not further reduce the risk. Calcium intake is inversely associated with the risk of gastrointestinal cancers in both men and women (RR 0.84; 95% CI in men and RR 0.77; 95% CI in women), and particularly with colorectal cancer.
    (National Institutes of Health-AARP-Diet and Health Study; Approximately 500,000 participants over 7 years; Park Park et al.; Dairy Food, Calcium, and Risk of Cancer in the NIH-AARP Diet and Health Study; Arch Intern Med. 2009;169(4):391-401)
• selenium
  • selenium It can activate the p53 tumor suppressor protein (through redox mechanisms) and the DNA repair arm of p53 in cancer prevention.
    (Seo YR et al.; selenomethionine regulation of p53 by a ref1-dependent redox mechanism; Proc Natl Acad Sci USA 2002; 99; 14548-14553)
  • selenium It can reduce the risk of cancer as well as progression and metastasis in all types of cancer (and especially in prostate, liver, gastrointestinal and lung cancer), particularly in people with low selenium status (it comes from u.a. leading to a reduction in DNA damage and oxidative stress).
    (Rayman MP; Selenium in cancer prevention: a review of the evidence and mechanism of action; Proc Nutr Soc 2005; 64; 527-542)
  • Low seleniumLow levels increase cancer incidence compared to high levels (OR 1.95) Cohort study with 4857 participants
    (Ujiie S et al.; Serum Selenium contents and the risk of cancer; Gan To Kagaku Ryoho 1998; 25; 1891-1897)
  • seleniumSupplementation increases antioxidant protection through enhanced expression of selenium-dependent GSH peroxidase and thioredoxin reductase. Selenium protects against cancer: it influences tumor metabolism, the immune system, cell cycle regulation, and apoptosis.
    (Combs GF Jr; Chemopreventive mechanism of selenium; Med Klin 199; 94 Suppl 3; 18-24)
  • selenium It has a protective effect on cancer incidence (RR 0.76), particularly pronounced in people with low selenium levels and in high-risk patients.
    (Meta-analysis; Lee EH et al.; Effects of selenium supplements on cancer prevention: meta-analysis of randomized controlled trials; Nutr Cancer 2011; 63; 1185-1195)
  • For people with the lowest seleniumIn individuals with low selenium levels, the risk of fatal cancer is 5.8 times higher compared to those with the highest selenium levels. In individuals with low selenium and low vitamin E levels, the risk was 11.4 times higher. Reduced intake of vitamin A or provitamin A increases the risk of lung cancer in smokers with low selenium levels.
    (Salonen JT et al.; isk of cancer in relation to serum concentrations of selenium and vitamins A and E: matched case-control analysis of prospective data; Br Med J 1985; 290; 4127-420)
  • Height seleniumSelenium levels (between 130 and 150 ng/ml) reduce overall mortality (HR 0.83), cancer mortality (HR 0.69), and cardiovascular mortality (HR 0.94). Very high selenium levels (&In contrast, levels above 150 ng/ml slightly increase mortality.
    (13887 participants; Bleys J et al.; Serum selenium levels and all-cause, cancer and cardiovascular mortality among US adults; Arch Intern Med 2008; 168; 4040-410)

ii) Cancer risk for individual tumor types

prostate

• selenium
  • Men who have a good long-term relationship with selenium People who are adequately supplied with selenium (measurement of selenium content in toenails) have a lower risk of prostate cancer.
    (Prospective cohort study; 58279 participants; Geybels MS et al.; Advanced prostate cancer risk in relation to nail selenium levels; J Natl Cancer Inst 2013; 105; 1394-1401)
  • A 63% lower risk of prostate cancer was found through selenium 200 mcg.
    (Randomized, double-blind, placebo-controlled; Clark LC et al.; Decreased incidence of prostate cancer with selenium supplementation; Br J Urol. 1998; 730-734 (cf.Original study evaluation from 1996 in JAMA 1996; 276; 1957-1963)
  • selenium 200 mcg is especially relevant for PSA. &<4 ng/ml and low selenium levels &< 123.2 ng/ml had a significant impact on the overall prostate cancer incidence (RR 0.51; 95% CI)
    (Randomized, placebo-controlled, double-blind; NPC trial; 1312 participants; Duffield-Lillico AJ et al.; Selenium supplementation, baselone plasma selenium status and incidence of prostate cancer; an analysis of the complete treatment period of the Nutritional Prevention of Cancer Trial; BJU international 2003; 91; 608-612)
  • Low seleniumHigh blood levels are associated with a 4-5 times increased risk of prostate cancer.
    (Case-control study; Baltimore Longitudinal Study of Aging; 148 participants; Brooks JD et al.; plasma sleenium level before diagnosis and the risk of prostate cancer development; The Journal of Urology; 2001; 166; 2034-2038)
  • Higher seleniumHigher levels are associated with a lower risk of advanced prostate cancer (OR 0.49; 95% CI for highest vs. lowest levels). After additionally controlling for family history of prostate cancer, BMI, calcium and saturated fat intake, vasectomy, and geographic region, the OR was 0.35 (95% CI).
    (Prospective Health Professionals case-control study; 51529 participants; Yoshizawa K et al.; Study of prediagnostic selenium level in toenails and the risk of advanced prostate cancer; J Natl Cancer Inst 1998; 90: 1219-1224)
  • Inorganic selenium In an experimental mouse model, high doses significantly reduce the growth of primary hormone-refractory prostate carcinomas and the development of retroperitoneal lymph node metastases.
    (Corcoran NM et al.; Inorganic selenium retards progression of experimental hormone refractory prostate cancer; J Urol 2004; 171: 907-910)
  • selenium reduces the risk of prostate cancer (RR 0.74).
    (Review, meta-analysis Etminan M et al.; Intake of selenium in the prevention of prostate cancer: a systemic review and meta-analysis; Cancer Causes Control 2005; 16; 1125-1131)
  • The risk of prostate cancer increases with rising seleniumThey reflect levels up to 170 ng/ml.
    (Hurst R et al.; Selenium and prostate cancer: systematic review and meta-analysis; Am J Clin Nutr July 2012vol. 96 no. 1 111-122)
  • Higher seleniumIncreased intake reduces the risk of prostate cancer.
    (Van den Brandt PA et al.; Selenium levels and the subsequent risk of prostate cancer: a prospective cohort study; Cancer Epidemiol Biomerkers Prevent 2003; 12; 866-871)
• Vitamin E
  • Vitamin E (+alpha-tocopheryl-succinate) and selenium Methylselenic acid alone leads to a moderate inhibition of the survival time and growth of human prostate cancer cells. A combination results in a dramatic increase in the growth inhibition of prostate cancer cells. This leads to the induction of apoptosis, an increase in Bax, Bak, and Bi proteins, and a decrease in Bcl-2 protein.
    (Reagan-Shaw S et al.; Combination of vitamin E and selenium causes an induction of apoptosis of human prostate cancer cells by enhancing Bax/Bcl-2 ratio; Prostate 2008; 68: 1624-1634)
  • The incidence of prostate cancer is reduced by 1/3 by Vitamin E 50 mg.
    (randomized, double-blind, placebo-controlled; ATBC study; Heinonen OP et al.); Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial; J Natl Cancer Inst 1998; 90: 440-446)
  • Smokers and former smokers who consume at least 100 IU Vitamin E Patients who received the treatment had a reduced risk of metastatic or fatal prostasis (RR 0.44; 95% CI).
    (47780 participants; Chan JM et al.; Supplemental Vitamin E Intake and Prostate Cancer Risk in a Large Cohort of Men in the United States; Cancer Epidemiology Biomarkers &&amp; Prevention 1999; 8; 893-899)
  • Supplementation with Vitamin E 400 IU barely reduced the overall prostate cancer risk (HR 0.86; 95% CI). The risk of advanced prostate cancer (regionally invasive or metastatic) decreased significantly depending on the dose of vitamin E (HR 0.43; 95% CI). No strong association was found between the administration of selenium (&< 50 mcg) and the risk of prostate cancer (HR 0.90; 95% CI)
    (Prospective cohort study; 35,242 participants over 10 years; Peters et al.; Vitamin E and selenium supplementation and risk of prostate cancer in the Vitamins and lifestyle (VITAL) study cohort; Cancer Causes Control 2008; 19: 75-87)
• Vitamin K2
  • There is a non-significant relationship between prostate cancer incidence and Vitamin K2The risk reduction is 35% (RR 0.65), and the risk of advanced prostate cancer is reduced by 63% (RR 0.37). The association with menaquinone from dairy products is more pronounced than with vitamin K2 from meat. Vitamin K1 (phylloquinone, primarily from leafy green vegetables and vegetable oil) shows no correlation.
    (EPIC study, 11319 participants over 8.6 years; Nimptsch K et al.; Dietary intake of vitamin K and risk of prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg); Am J Clin Nutr 2008; 87; 985-992)
• tomatoes
  • The risk of prostate cancer is reduced with a high intake of raw foods. tomatoes (RR 0.89; 95% CI) and stronger for cooked tomato products (RR 0.81; 95% CI).
    (Meta-analysis of 11 case-control studies and 10 cohort studies; Etminan M et al.; The Role of Tomato Products and Lycopene in the Prevention of Prostate Cancer: A Meta-Analysis of Observational Studies; Cancer Epidemiology Biomarkers) &&amp; Prevention 2004; 13; 340-345)
• soy
  • Soy isoflavones Two studies showed that these drugs can reduce the risk of prostate cancer (RR 0.49; 95% CI).
    (Van Die MD et al.; Soy and soy isoflavones in prostate cancer: a systematic review and meta-analysis of randomized controlled trials.)
  • Japanese people have a 7-110 times higher Isoflavonoid-Levels as Finnish. The high phytoestrogen levels may inhibit the growth of prostate cancer in Japanese men and explain the low mortality rate from prostate cancer in Japan.
    (Adlerkreutz H et al.; Plasma concentrations of phyto-estrogens in Japanese men; Lancet 1993; 342; 1209-1210)
• Fish (Omega 3 fatty acids EPA and DHA)
  • Fish supply Consuming fish oil more than three times a week reduces the risk of prostate cancer, and especially the risk of metastatic prostate cancer (RR 0.56; 95% CI). Each 0.5 g intake of fish oil is associated with a 24% risk reduction for metastatic prostate cancer.
    (Health professionals follow-up study; 47882 participants over 12 years; Augustsson K et al.); A Prospective Study of Intake of Fish and Marine Fatty Acids and Prostate Cancer; Cancer Epidemiology Biomarkers &&amp; Prevention 2003; 12; 64-67)
  • Men who don't Fish Men who eat fish have a 2-3 times higher risk of prostate cancer than men who eat moderate or high amounts of fish.
    (Prospective cohort study; 6272 participants over 30 years; Terry P et al.; Fatty fish consumption and risk of prostate cancer; The Lancet 2001; 357; 1764)

Gynecological tumors/Breast cancer

• Western lifestyle
  • Asian-American women born in the West and western lifestyle Those who migrate from Eastern Europe have at least a 60% higher risk of breast cancer than controls born in the East, regardless of whether their ancestors were born in the West or East. Among emigrants born in the East, those from urban areas have a 30% higher risk than emigrants from rural areas. (A breast cancer risk increased up to sixfold by migration has been observed.)
    (Case-control study; 1563 participants; Ziegler RG et al.; Migration patterns and breast cancer risk in Asian-American women; JNCI 1993; 85; 1819-1827)
• Body weight/obesity
  • The risk of breast cancer increases by 45% in women who gain at least 25 kg of body weight after the age of 18. Weight gain have – and by 18% in women who gained approximately 11 kg after menopause. 15% of all breast cancer cases can be attributed to a weight gain of at least 2 kg after menopause. dem18.LJ and 4.4% of cases are attributed to a weight gain of at least 2 kg after menopause. Women who have lost at least 11 kg after menopause have a 57% lower risk of breast cancer.
    (Prospective cohort study; Nurses Health Study; 87143 participants; Eliassen AH et al.; Adult Weight Change and Risk of Postmenopausal Breast Cancer; JAMA 2006; 296; 193-201)
  • High-fat diet (with little bread and fruit juices) significantly doubles the risk of breast cancer compared to low fat consumption (HR 2.0; 95% CI).
    (EPIC study; 15351 participants; Schulz M et al.; Identification of a dietary pattern characterized by high-fat food choices associated with increased risk of breast cancer: the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study; British Journal of Nutrition 2008; 100; 942-946)
• Carotenoids
  • Carotenoids: No general relationship was found between postmenopausal overall breast cancer and micronutrient intake. Dietary beta-carotene reduces the risk of lobular breast cancer (IRR 0.72). Vitamin E Reduces the risk of estrogen receptor- and progesterone receptor-positive breast cancer (IRR 0.50). Dietary Folic acid Potentially increases the risk of estrogen receptor- and progesterone receptor-positive breast cancer (IRR 1.27).
    (Prospective cohort study; 26224 participants; Roswall N et al.; Micronutrient intake and breast cancer characteristics among postmenopausal women; Eur J Cancer Prev 2010; 19: 360-365)
  • Carotenoids: Dietary alpha (RR 0.83) and beta-carotene (RR 0.78) as well as lycopene (RR 0.85) correlate inversely with the risk of estrogen- and progesterone receptor-positive breast cancer. Vitamin E Vitamin C intake does not correlate with breast cancer risk. Vitamin C intake has a weak positive association with breast cancer in general.
    (84,805 participants; Cuii Y et al.; Selected antioxidants and risk of hormone receptor-defined invasive breast cancers among postmenopausal women in the Women's Health Initiative Observational Study; At J Clin Nutr. 2008; 87: 1009-1018)
  • CarotenoidsDietary carotenoids do not correlate with the overall risk of breast cancer. Dietary alpha- and beta-carotene correlate inversely with the risk of estrogen- and progesterone receptor-negative breast cancer in smokers (RR 0.32 and RR 0.35, respectively) and in women who do not take supplements.
    (Cohort study; 36664 participants over 9.4 years; Larsson SC et al.; Dietary carotenoids and risk of hormone receptor-defined breast cancer in a prospective cohort of Swedish women; Eur J Cancer 2010; 46: 1079-1085)
  • CarotenoidsThe concentrations of total carotenoids, beta-carotene, lycopene, and lutein were significantly lower in cancer patients than in healthy controls. The risk of breast cancer was greatly reduced for beta-carotene (OR 0.41), lycopene (OR 0.55), and total carotenoids (OR 0.55) between the highest and lowest blood levels.
    (Case control study; 590 participants; Sato R et al.; Prospective study of carotenoids, tocopherols, and retinoid concentrations and the risk of breast cancer; Cancer Epidemiol Biomarkers Prev 2002; 11: 451-457)
• Folic acid
  • Low Folate levels are associated with an increased risk of prostate cancer (HR 4.79) and an increased risk of breast cancer (HR 6.46).
    (Cohort study; 1988 participants over more than 20 years; Rossi E et al.; Folate levels and cancer morbidity and mortality: prospective cohort study from Busselton, Western Australia; Ann Epidemiol 2006; 16; 206-212)
  • Higher intake of Folate, B12 or methionine is associated with a reduced risk of ER- breast cancer (ER- = estrogen receptor-negative).
    (Yang D et al.; Dietary intake of folate, B-vitamins and methionine and breast cancer risk among Hispanic and non-Hispanic white women. PLoS One. 2013;8(2):e54495.)
  • The excessively increased risk of breast cancer from increased alcohol consumption is counteracted by adequate intake of Folic acid reduced (RR for 600 mcg folic acid per day versus 150 - 299 mcg was 0.55, 95% CI).
    (Prospective cohort study over 16 years; 88,818 participants from the Nurses' Health Study;
    Zhang S et al.; A Prospective Study of Folate Intake and the Risk of Breast Cancer; JAMA 1999; 281; 1632-1637)
• Cysteine
  • High mirrors of Cysteine (Precursors of glutathione) or NAC are significantly associated with a reduced risk of breast cancer in a dose-dependent manner (RR 0.44; 95% CI for highest vs. lowest levels).
    (Prospective Nurses Health Study; 32826 participants; Zhang SM et al.; A prospective study of plasma total cysteine ​​and risk of breast cancer; Cancer Epidemiol Biomarkers Prev 2003; 12: 1188-1193)
• Omega 3 fatty acids (EPA and DHA)
  • There is clear evidence for the inverse relationship between the intake of Omega 3 fatty acids and the risk of breast cancer. Omega-3 fatty acids reduce the risk by 14%. For every 0.1 g increase in omega-3 fatty acid intake, the risk decreased by 5%.
    (Meta-analysis of 26 publications with 883,585 participants; Zheng JS et al.; Intake of fish and marine n-3-polyunsaturated fatty acids and risk of breast cancer: meta-analysis of data from 21 independent prospective cohort studies; BMJ 2013; 346; f37062)
  • Fish oil Reduces the risk of ductal (HR 0.68), but not of lobular breast cancer.
    (Cohort study; 35016 participants over 3 years; Brasky TM et al.; Specialty supplements and breast cancer risk in the VITamins And Lifestyle (VITAL) Cohort; Cancer Epidemiol Biomarkers Prev 2010; 19: 1696-1708)
&Soy/Isoflavones
• Increased Soy intake significantly reduces breast cancer risk in Asians: When taking &For 19 mg of isoflavones, the OR is 0.71 (29% reduction), and for an intake of approximately 10 mg, the OR is 0.88 compared to an intake of &< 5 mg. The risk decreases by approximately 16% for every 10 mg of isoflavone intake – in pre- and postmenopausal cancer. (In 11 studies with a Western population and low soy intake of 0.8-0.15 mg of isoflavones per day, no correlation was found between soy intake and breast cancer risk).
  (Meta-analysis of 1 cohort and 7 case-control studies; Wu AH et al.; Epidemiology of soy exposures and breast cancer risk; British Journal of Cancer 2008; 98, 9-14; doi:10.1038/sj.bjc.6604145)
• Frequent consumption of miso soup and Isoflavones is associated with a lower risk of breast cancer in Japanese women (OR 0.46; 95% CI comparing the lowest and highest intakes), particularly in postmenopausal women.
  (Prospective JPHC cohort study; 21852 participants; Yamamoto S et al.; Soy, Isoflavones, and Breast Cancer Risk in Japan; Journal of the National Cancer Institute 2003; 95; 906-913)
• The level of intake of soy In contrast, high intake during adolescence is associated with breast cancer risk in both pre- and postmenopausal Chinese women (OR 0.51; 95% CI for the highest versus lowest intake).
  (Case-control study; 3015 participants; Shu XO et al.; Soyfood Intake during Adolescence and Subsequent Risk of Breast Cancer among Chinese Women ; Cancer Epidemiology, Biomarkers &&amp; prevention; 2001; 10; 483-488)
• The excretion of Isoflavonoids and lignans The risk of breast cancer is significantly lower in women with breast cancer compared to controls. With increasing excretion of isoflavonoids and lignans, the risk of breast cancer decreases (OR 0.62, 0.40, and 0.28, respectively; 95% CI for the highest versus the lowest intake of isoflavonoids, lignans, and isoflavonoids and lignans).
  (Case control study; Shanghai Breast Cancer Study; 250 participants; Dai Q et al.; Urinary Excretion of Phytoestrogens and Risk of Breast Cancer among Chinese Women in Shanghai; Cancer Epidemiology, Biomarkers &&amp; Prevention 2002; 11; 815-821)
• There is a significant reduction in risk in women through a high intake of phytoestrogens (isoflavones, lignans).
  (Randomized case-control study; Ingram D. et al.; Case-control study of phyto-estrogens and breast cancer; Lancet. 1997; 350; 990-994)
• Soy isoflavones reduce free estradiol and estrone levels in premenopausal women (in 53.9% of cases compared to 37.5% in controls). SHBG levels increase (by 41.4% compared to 37.5% in controls). The menstrual cycle lengthens by 3.5 days compared to controls, and the follicular phase by 1.46 days. Longer cycles or a lower number of cycles are associated with a lower risk of breast cancer.
  (Double-blind, placebo-controlled; 66 participants; Kumar NB et al.; The specific role of isoflavones on estrogen metabolism in premenopausal women; Cancer 2002; 94; 1166-1174)
• Soy and its components may reduce the risk of breast cancer when consumed regularly (regarding soy protein OR 0.39 for premenopausal and OR 0.22 for postmenopausal women, and regarding tofu OR 0.23 for premenopausal women; 95% CI in each case).
  (Kim MK et al.; Dietary intake of soy protein and tofu in association with breast cancer risk based on a case control study; Nutr Cancer 2008; 60: 568-576)
• In postmenopausal American women, the risk of breast cancer decreases with the intake of flavonoids, most strongly through flavonols (OR=0.54; 95% CI), flavones (OR=0.61), flavan-3-ols (OR=0.74) and lignans (OR=0.69).
  (Case control study; 2874 participants; Fink BN et al.; Dietary flavonoid intake and breast cancer risk among women on Long Island; Am J Epidemiol 2007; 165: 514-523)
• In pre- and postmenopausal American breast cancer patients, overall mortality decreases with high intake of Flavonoids Compared to low intake, the strongest effects were observed for flavones (OR=0.63; 95% CI), anthocyanins (OR=0.64), and isoflavones (OR=0.52). Similar results were found for cancer-specific mortality.
  (Cohort study; 1210 participants over more than 5 years; Fink BN et al.; Dietary Flavonoid Intake and Breast Cancer Survival among Women on Long Island; Cancer Epidemiology Biomarkers) &&amp; Prevention 2007; 16, 2285-2292)
• Green tea
  • Women who regularly green tea Those who drink tea have a significantly reduced risk of breast cancer, which is clearly inversely correlated with the amount of tea consumed.
    (Case-control study; 2018 participants; Zhang M et al.; Green tea and the prevention of breast cancer: a case-control study in southeast China; Carcinogenesis 2007; 28; 1074-1078)
• Carotenoids
  • The risk of breast cancer was lower in the group with the highest intake of beta-carotene, lycopene, and totalCarotenoids approximately half the size of the group with the lowest recording.
    (Prospective case-control study; 590 participants; Sato R et al.; Prospective Study of Carotenoids, Tocopherols, and Retinoid Concentrations and the Risk of Breast Cancer; Cancer Epidemiology Biomarkers &&amp; Prevention 2002; 11; 451-457)
  • The combined high intake of carotenoids (OR 0.57 ; 95% CI for beta-carotene in women not on HRT) and the Omega 3 fatty acid DHA Docosahexaenoic acid (OR 0.52; 95% CI in postmenopausal women) reduces the risk of breast cancer.
    (Case-control study; 843 participants; Nkondjock A et al.; Intake of specific carotenoids and essential fatty acids and breast cancer risk in Montreal, Canada ; Am J Clin Nutr 2004; 79; 857-864)
  • High levels of alpha- and beta-carotene, lutein, zeaxanthin, lycopene, and total carotenoids reduce the risk of breast cancer. For some carotenoids (z.B. Beta-carotene) the associations are stronger for estrogen receptor-negative than for estrogen receptor-positive tumors.
    (Eliassen AH et al.; Circulating carotenoids and risk of breast cancer: pooled analysis of eight prospective studies. J Natl Cancer Inst. 2012; 104(24):1905-16.)
• Calcium and Vitamin D
  • In women who had not previously taken calcium or vitamin D, Calcium and vitamin D together significantly reduce the risk of breast and colorectal cancer..
    (15,646 women in the WHI study; Bolland MJ et al.; Calcium and vitamin D supplements and health outcomes: a reanalysis of the Women's Health Initiative (WHI) limited-access data set. Am J Clin Nutr 2011; 94:1144-9)
    There is a significant inverse relationship between Vitamin D-mirrors or Calcium-levels and the risk of breast cancer.
    (Meta-analysis; Chen P et al.; Meta-analysis of vitamin D, calcium and the prevention of breast cancer; Breast Cancer Res Treat 2010; 121; 469-477)
  • The CalciumIntake correlates significantly inversely with the risk of estrogen- and progesterone receptor-negative breast cancer (RR 0.66).
    (Prospective cohort study; 61,433 participants over 17.4 years; Larsson SC et al.; Long-term dietary calcium intake and breast cancer risk in a prospective cohort of women; Am J Clin Nutr 2009; 89: 277-282)
• Choline/Betaine
  • In China, a significant inverse association was found between the intake of Choline and Betaine and the risk of breast cancer, especially in women with low folate levels.
    (Zhang CX et al.; Choline and betaine intake is inversely associated with breast cancer risk: a two-stage case control study in China. Cancer Sci. 2013; 104(2):250-8.)
• selenium
  • Lower levels are found in women with breast cancer. seleniumconcentrations higher than in healthy individuals (81.1 mcg/l versus 98.5 mcg/l).
    (Lopez-Saez Jb et al.; Selenium in breast cancer; Oncology 2003; 64; 227-231)
  • Women with BRCA1 mutations have an increased risk of breast and ovarian cancer. This BRCA1 mutation increases susceptibility to DNA breaks. seleniumSupplementation reduces the number of DNA breaks in mutation carriers to the number found in non-carrier controls.
    (Kowalska E et al.; Increased rates of chromosome breakage in BRCA1 carriers are normalized by oral selenium supplementation; Cancer Epidemiol Biomarkers Prev 2005; 14; 1302-1306)
• zinc
  • zinc has in supplementation &Over 10 years, a significant positive effect was observed in premenopausal breast cancer. Multivitamins as well as Vitamin C, E and Beta-carotene have during supplementation > 10 years in postmenopausal breast cancer a significant positive effect.
    (Retrospective case-control study; 7824 participants; Pan SY et al. Antioxidants and breast cancer risk – a population-based case-control study in Canada. BMC Cancer. 2011;11:372)

lung

• Carotenoids and Vitamin A
  • The recording of green vegetables, beta-carotene-rich vegetables, watermelons, vitamin A and carotenoids is inversely associated with the risk of lung cancer (HR 0.72 for the highest versus the lowest intake).
    (Takata Y et al.; Intakes of fruits, vegetables, and related vitamins and lung cancer risk: results from the Shanghai Men's Health Study (2002-2009). Nutr Cancer. 2013;65(1):51-61)
• Folic acid and vitamin C
  • Significant protective effects were found for Folic acid and vitamin C.
    (Cohort study over 6.3 years; 58,279 participants; Voorrips LE et al.; A Prospective Cohort Study on Antioxidant and Folate Intake and Male Lung Cancer Risk; Cancer Epidemiology Biomarkers) &&amp; Prevention 2000; 9, 357-365)
• Vitamin B6
  • Height Vitamin B6 levels reduce the risk by half (odds ratio 0.51; 95% CI).
    (Case-control study; Hartman TJ et al.; Association of the B Vitamins Pyridoxal 5'-Phosphate (B6), B12, and Folate with Lung Cancer Risk in Older Men; Am J Epidemiol 2001; 153; 688-694)
• selenium
  • Administering 200 mcg selenium (Selenium yeast) has been found to significantly reduce the incidence of lung cancer by 45% (95% CI)
    (Randomized; multicenter, double-blind, placebo-controlled: 1312 participants over 8 years; Clark LC et al.; Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group; JAMA 1996; 276; 1957-1963)
  • A low seleniumStatus is linked to an increased risk of lung cancer.
    (Cohort study, 500 participants; Hartman TJ et al.; Selenium concentration and lung cancer in male smokers; Cancer causes Control 2002; 123; 923-928)
  • Low seleniumMirrors are linked to an increased risk of lung cancer.
    (120 participants; Zhuo H et al.; Serum and lung tissue selenium measurements in subjects with lung cancer from Xuanwei, China; Zhogguo Fei Al Za Zhi 2011; 14; 39-42)
  • selenium It has a preventive effect against lung cancer in people with low selenium levels. It reduces cisplatin-induced nephrotoxicity and side effects of radiation therapy in lung cancer patients.
    (Review; Fritz H et al.; Selenium and lung cancer: a systemic review and meta analysis; PLoS One 2011; 6; #26259)
  • For people with the lowest seleniumPeople with low selenium levels have a 5.8-fold increased risk of fatal cancer compared to those with the highest selenium levels. In people with low selenium and low cholesterol levels, the risk is also significantly higher. Vitamin E-Levels were increased 11.4-fold. A reduced intake of Vitamin A or provitamin A increases the risk of lung cancer in smokers with low selenium levels.
    (Salonen JT et al.; isk of cancer in relation to serum concentrations of selenium and vitamins A and E: matched case-control analysis of prospective data; Br Med J 1985; 290; 4127-420)
• red wine
  • The risk of lung cancer decreased by 60% in smokers who smoked moderately once a day. red wine No risk reduction was observed with the consumption of beer, white wine, or liqueur.
    (California Men''s Health Study with 84,170 participants; Chao C et al.; Alcoholic Beverage Intake and Risk of Lung Cancer: The California Men's Health Study; Cancer Epidemiol Biomarkers Prev 2008; 17: 2692-2699)
• Phytoestrogens (such as Ashwagandha)
  • The risk of lung cancer decreases with increasing intake of Phytoestrogens (more clearly for Isoflavones as for phytosterols) in food by up to 46% (95% CI).
    (Case-control study; 3409 participants over 8 years; Schabath MB et al; Dietary Phytoestrogens and Lung Cancer Risk; JAMA 2005; 294:1493-1504)
• Flavones and proanthocyanidins
  • For the occurrence of lung cancer in postmenopausal women, an inverse relationship was found between the intake of Flavanones and ProanthocyanidinsIn female smokers and former smokers with very high intakes of flavanones and proanthocyanidins, a significantly lower incidence of lung cancer was observed than in female smokers and former smokers with very low intakes. Women who ingested higher amounts of isoflavones were less likely to develop cancer.
    (34.708 participants over 18 years of age; Cutler GJ; Dietary flavonoid intake and risk of cancer in postmenopausal women: the Iowa Women's Health Study; Int J Cancer. 2008 Aug 1;123(3):664-671)

Gastrointestinal tract (including liver and pancreas)

• apples
  • The odds ratio for the incidence of oral and pharyngeal cancer is [value] for the intake of [substance]. > 1 Apple/day opposite &< 1 apple/day 0.79 as well as 0.75 from esophagus, 0.80 from colon and rectum, 0.58 from larynx, 0.82 from breast, 0.85 from ovary and 0.91 from prostate (each 95% CI).
    (Case-control study; 14,138 participants over 11 years; Gallus S et al.; Does an apple a day keep the oncologist away? Annals of Oncology 2005; 16: 1841-1844)
  • Fresh Apple 100g has the same antioxidant activity as 1500 mg of vitamin C and extract from whole apples inhibits the growth of colon and liver cancer in vitro in a dose-dependent manner.
    (Eberhardt MV et al.; Antioxidant activity of fresh apples; Nature 2000; 405: 903-904)
• Flavonoids
  • Flavonoids (Apagenin 20 mg and epigallocatechin gallate 20 mg) reduce the recurrence rate after curative treatment
    Colon cancer surgery (0% compared to 20% in the control group; evidence level 2B).
    (87 participants over 3-4 years; Hoensch H et al.; Prospective cohort comparison of flavonoid treatment in patients with resected colorectal cancer to prevent recurrence; World J Gastroenterol 2008; 14; 2187-2193)
• tomatoes
  • Intake of larger quantities of tomatoesThese products reduce the risk of stomach cancer.
    (Yang T et al.; The role of tomato products and lycopene in the prevention of gastric cancer: a meta-analysis of epidemiologic studies. Med hypotheses. 2013; 80(4):383-8)
• Carotenoids
  • The risk of stomach cancer is inversely correlated with blood levels of antioxidants. Beta-carotene (R 0.31), vitamin E (R 0.89), alpha-carotene (R 0.67), lycopene (R 0.56) and vitamin C (R 0.61).
    (634 participants; Tsubonon Y et al.; Plasma antioxidant vitamins and carotenoids in five Japanese populations with varied mortality from gastric cancer; Nutr Cancer 1999; 34; 56-61)
  • Lycopene This leads to a 31% significant reduction in the risk of pancreatic cancer (OR 0.69; 95% CI). Beta-carotene (OR 0.57; 95% CI) and Total carotenoids (OR 0.58; 95% CI) significantly reduce the risk only in non-smokers.
    (Case-control study with 5183 participants over 3 years; Nkondjock A et al.; Dietary intake of lycopene is associated with reduced pancreatic cancer risk; Nutr 2005; 135: 592-597)
• Vitamins A and C
  • Patients who Vitamin AThose taking supplements containing [ingredient name] have a reduced risk of stomach cancer (RR = 0.4; 95% CI). An inverse relationship was found between [ingredient name] and [ingredient name]. Vitamin C-Intake and stomach cancer (RR 0.7; 95% CI for highest versus lowest intake)
    (Netherlands Cohort Study; 120852 participants over 6.3 years; Botterweck AA et al.; Vitamins, carotenoids, dietary fiber, and the risk of gastric carcinoma: results from a prospective study after 6.3 years of follow-up; Cancer 2000; 88; 737-748)
• magnesium
  • magnesium It significantly reduces the risk of colon cancer.
    (Prospective study with 35,196 participants over 17 years; Folsom AR et al.; Magnesium Intake and Reduced Risk of Colon Cancer in a Prospective Study of Women; Am J Epidemiol 2006; 163; 232-235)
• selenium
  • Administering 200 mcg selenium (Selenium yeast) showed a significant reduction in colon cancer incidence of 58% (95% CI).
    (Randomized; multicenter, double-blind, placebo-controlled: 1312 participants over 8 years; Clark LC et al.; Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group; JAMA 1996; 276; 1957-1963)
  • There is an inverse relationship between seleniumblood levels and risk for esophageal and stomach cancer.
    (Prospective cohort study; 120,852 participants; Steevens J et al.; Selenium status and the risk of esophageal and gastric cancer subtypes: the Netherlands cohort study; Gastrenterology 2010; 138; 1704-1713)
  • Height seleniumHigh levels of cadmium, arsenic, and lead reduce the risk of exocrine pancreatic cancer (high levels of cadmium, arsenic, and lead increase it).
    (517 participants; Amarai AF et al.; Pancreatic cancer risk and levels of trace elements; Gut 2011)
  • 500 mcg selenium Over 3 years, it increases selenium levels and GPx activity and significantly reduces liver cancer incidence in high-risk patients.
    (Placebo controlled; 2065 participants; Li H et al.; The prevention of liver cancer by selenium in high risk populations; Zhonghua Yu Fang Yi Xue Za Zhi 2000; 34; 696-703)
  • Men with low seleniumThose with this status have an increased risk of colorectal cancer (OR for highest versus lowest levels = 0.68; 95% CI).
    (Case-control study; 1609 participants; Takata
• Selenium and Vitamin C
  • Low serum levels of Selenium, zinc, manganese, vitamin C and vitamin E They increase the risk of gallbladder cancer.
    (Shukla VK et al.; Micronutrients, antioxidants, and carcinoma of the gallbladder; J Surg Oncol 2003; 84; 31-35)
  • Height Vitamin CHigh cholesterol intake reduces the risk of pancreatic cancer (OR 0.45; 95% CI), while high cholesterol significantly increases it.
    (109 participants; Lin Y et al.; Nutritional factors and risk of pancreatic cancer: a population-based case-control study based on direct interview in Japan; J Gastroenterol 2005; 40: 297-301)
• Folic acid
  • The recording of Folic acid 71-660 μg/day (via supplements or food) is not associated with increased risk of colon cancer Folic acid reduces the risk by 19%.
    (Cancer Prevention Study II Nutrition Cohort; 99521 participants; Stevens VL et al.; High Levels of Folate, from Supplement and Fortification, are not associated with increased risk of colorectal cancer; Gastroenterology 2011; published ahead of print; doi: 10.1053/j.gastro.2011.04.004)
  • Colorectal tumors: The risk is higher in Women inversely proportional to the intake of Iron, folic acid and vitamin CFolic acid is the best protective factor. men was a high supply of Calcium and Vitamin E associated with a reduced risk, with vitamin being the most effective (RR 0.35; 95% CI).
    (Case-control study; Tseng M et al.; Micronutrients and the risk of colorectal adenomas; American Journal of Epidemiology, Vol 144, Issue 11 1005-1014)
  • Low FolateIn cell cultures, elevated levels increase the risk of DNA damage to colon cells (and the increase in proteins such as Nit2 and COMT), and thus the risk of colon cancer.
  • Height Folic acidIntake from food significantly reduces the risk of pancreatic cancer (multivariable rate ratio 0.25; 95% CI).
    (81,922 participants over 6.8 years; Larsson SC et al.; Folate intake and pancreatic cancer incidence: a prospective study of Swedish women and men; J Natl Cancer Inst 2006; 98: 407-413)
    (Duthie SJ et al.; The response of human coloncytes to folate deficiency in vitro: functional and proteomic analyses; J Proteome Res 2008; 7; 3254-3266)
• Calcium and Vitamin D
  • In women who have not previously taken calcium or vitamin D, lower Calcium and Vitamin D Together, they significantly increase the risk of breast cancer and colorectal cancer.
    (15,646 women in the WHI study Bolland MJ et al.; Calcium and vitamin D supplements and health outcomes: a reanalysis of the Women's Health Initiative (WHI) limited-access data set. Am J Clin Nutr 2011; 94:1144-9)
  • Colorectal adenomas: There is evidence that the Calcium and Vitamin D-Intake is inversely proportional to the frequency of colorectal adenomas.
    (Randomized multicenter study; polyp prevention trial; 1,905 participants; Hartman TJ et al.; The Association of Calcium and Vitamin D with Risk of Colorectal Adenomas; J Nutr 2005; 135: 252-259)
• Vitamin D
  • The 25(OH)DVitamin D levels are inversely related to the risk of colorectal cancer (an increase of 20ng/ml reduces the risk by 43%).
    (Meta-analysis; Yin L et al.; Meta-analysis: longitudinal studies of serum vitamin D and colorectal cancer risk; Aliment Pharmacol Ther 2009; 30; 113-125)
  • A high intake of Vitamin D (over 25 mcg/day) or a vitamin D serum level of 33 ng/ml reduces the risk of colon cancer by 50% (Note: Vitamin D increases calcium absorption in the intestine).
    (Gorham ED et al.; Vitamin D and prevention of colorectal cancer; J Steroid Biochem Mol Biol 2005; 97; 179-194)
  • High absorption and serum levels of Vitamin D are associated with a significant reduction in the risk of colorectal cancer.
    (Review of epidemiological studies; Grant WB et al; A critical review of studies on vitamin D in relation to colorectal cancer. Nutrition and Cancer 2004; 48: 115-123)
  • The risk of colorectal cancer is higher with values ​​of 25-Hydroxy-Vitamin D Levels above 33 ng/ml were reduced by half compared to levels below 2 ng/ml (RR 0.49; 95% CI).
    (Meta-analysis of 5 studies; Gorham ED et al. “Optimal Vitamin D Status for Colorectal Cancer Prevention: A Quantitative Meta Analysis.” Am J Prev Med 2007; 32: 210-216)
  • Vitamin DUptake and levels are inversely associated with the risk of colorectal cancer.
    (Ma Y et al.; Association between vitamin D and risk of colorectal cancer: a systematic review of prospective studies. J Clin Oncol.2011; 29(28):3775-82)
  • Rectal cancer: The risk is highly dependent on the Calcium-Intake (RR 0.59 with high calcium intake compared to RR 1.00 with low intake) and the Vitamin D3-Intake (RR 0.76 compared to RR 1.00 with low intake). For calcium and vitamin D3 together, the risk reduction was 45% (RR 0.55).
    (9-year cohort study; 34,702 postmenopausal women; Zheng W et al.; A prospective cohort study of intake of calcium, vitamin D, and other micronutrients in relation to incidence of rectal cancer among postmenopausal women; Cancer Epidemiol Biomarkers Prev. 1998; 7: 221-225)
  • Vitamin D influences the pathogenesis of pancreatic carcinoma (RR 0.59 at the highest compared to the lowest intake).
    (Health Professionals Follow-up Study with 46,771 men; Nurses''' Health Study with 75,427 women; Skinner HG et al.; Vitamin D intake and the risk for pancreatic cancer in two cohort studies; Cancer Epidemiol Biomarkers Prev 2006; 15: 1688-1695)
• Vitamin K2
  • Vitamin K2 It is beneficial in the prevention of hepatocellular carcinoma in women with viral cirrhosis (OR 0.13; 95% CI).
    (Habu D et al.; Role of vitamin K2 in the development of hepatocellular carcinoma in women with viral cirrhosis of the liver. JAMA 2004 Jul 21;292(3):358-61.)
• Methionine
  • Higher intake of Methionine significantly reduces the risk of pancreatic cancer (multivariate rate ratio 0.44; 95% CI).
    (81,022 participants over 7.2 years; Larsson SC et al.; Methionine and vitamin B6 intake and risk of pancreatic cancer: a prospective study of Swedish women and men; Gastroenterology 2007; 132: 113-118)
  • The recording of Folate or methionine is conversely associated with the risk of colorectal cancer.
    (Razzak AA et al.; Associations between intake of folate and related micronutrients with molecularly defined colorectal cancer risks in the Iowa Women's Health Study. Nutr Cancer. 2012;64(7): 899-910)
• Glutathion
  • Glutathion Consuming certain foods reduces the risk of oral and pranyx cancer by 50%.
    (Jones DP; Glutathione distribution in natural products: absorption and tissue distribution; Methods in Enzymology 1995; 25; 3-13)
• Fish (Omega 3 fatty acids EPA and DHA)
  • The height of the Fish consumption is conversely associated with colorectal cancer.
    (Wu S et al.; Fish consumption and colorectal cancer risk in humans: a systematic review and meta-analysis. Am J Med. 2012; 125(6):551-9.e5)

urology

• Carotenoids
  • Taking into account various influencing factors such as smoking and age of the participants, the odds ratio of developing bladder cancer was compared with Carotenoids The following carotenoids were identified as protective substances: alpha-carotene 0.22, lutein 0.42, lycopene 0.94, and beta-cryptoxanthin 0.90. Regarding the combined effect of plasma carotenoids and smoking, the odds ratio for smokers with low lutein levels was 6.22 and low zeaxanthin levels was 5.18. The study results suggest that carotenoids may protect against bladder cancer. Smokers, in particular, could benefit from a higher carotenoid intake.
    (Case-control study; 448 participants over 4 years; Hung RJ et al.; Protective effects of plasma carotenoids on the risk of bladder cancer; J Urol 2006; 176: 1192-1197)
• Fish (Omega 3 fatty acids EPA and DHA)
  • Fatty sea fish (such as mackerel, herring, sardines, salmon) rich in omega-3 fatty acids Vitamin D supplementation at least once a week significantly reduces the risk of kidney cancer (OR 0.56) compared to the control group. With a corresponding diet lasting more than 10 years, the risk decreases even further (OR 0.26).
    (Cohort study with 61,433 participants over 15 years; Wolk A et al.; Long-term Fatty Fish Consumption and Renal Cell Carcinoma Incidence in Women; JAMA 2006; 296:1371-1376)
  • There is an inverse relationship between consumption. fatty fish with a risk of renal cell carcinoma (risk 0.26 with regular consumption of fatty fish compared to no fish intake), but no association with the consumption of lean fish.
    (Swedish Mammography Cohort Study; 61,433 participants over 10 years; Wolk A et al.; Long-term fatty fish consumption and renal cell carcinoma incidence in women; JAMA 2006; 20; 296: 1371-1376)
• selenium
  • There is an inverse relationship between seleniumconcentration and bladder cancer risk.
    (Case-control study; 540 participants; Kellen E et al.; Selenium is inversely associated with bladder cancer risk; a report form the Belgian case-control study on bladder cancer; Int J Urol 2006; 13; 1180-1184)
  • The seleniumConcentration is inversely related to the risk of bladder cancer in women.
    (Case-control study; 679 participants; Michaud DS et al.; Toenail selenium concentrations and bladder cancer risk in woman and men; Brit J Cancer 2005; 93; 443-458)
  • There is an inverse relationship between seleniummirror and bladder cancer risk.
    (Prospective cohort study; 120,852 participants; Zeegers MP et al.; Prediagnostic toenail selenium and risk of bladder cancer; Cancer Epidemiol Biomarkers Prev 2002; 11; 1292-1297)
  • People with high seleniumPeople with diaphragmatic bladders have a lower risk of bladder cancer. Folic acid or a high intake of fruit reduces the risk in smokers.
    (Altwein JE; Primary prevention of bladder cancer; What's new? Urologist A 2007; 46; 616-621)
  • A high seleniumStatus significantly reduces the risk of bladder cancer by 39% (Or 0.61; 95% CI).
    (Meta-analysis of 7 epidemiological studies; Amarai M et al.; Selenium and bladder cancer risk: a meta-analysis; Cancer Epidemiol Biomarkers Prev 2010; 19; 2407-2415)
  • selenium It protects at-risk groups such as smokers, women and people with a mutation of the p53 gene from bladder cancer.
    (1,875 participants; Wallace K et al.; Selenium and risk of bladder cancer: a population-based case-control study; Cancer Prev Res 2009; 2; 70-73)

hematology

• Carotenoids and glutathione
  • Leukemia (hematological neoplasm): The intake of vegetables (OR 0.53; 95% CI), protein sources (OR 0.40; 95% CI) and fruits (OR 0.71; 95% CI) and especially Carotenoids (OR 0.65; 95% CI) and antioxidant Glutathion (OR 0.43; 95% CI) through the mother is inversely associated with acute lymphoblastic leukemia (ALL) in children (ALL can originate in utero).
    (Population-based Northern California Childhood Leukemia Study; 276 participants; Jensen CD et al.; Maternal dietary risk factors in childhood acute lymphoblastic leukemia; Cancer Causes and Control 2004; 15; 559-570)
• Iron and folic acid
  • Acute lymphoblastic leukemia (hematological neoplasm): In children aged 0-14 years, a correlation has been observed between... iron- or Folic acidSupplementation during pregnancy was associated with an increased risk of developing ALL in the child (OR 0.37; 95% CI). For iron alone, the odds ratio is 0.75.
    (249 participants over 10 years of age; Thompson JR et al.; The Lancet 2001; 358; 9297)
• Polyunsaturated fatty acids and vitamin D
  • An inverse relationship has been found between the risk of non-Hodgkin lymphoma (hematological neoplasms) and the intake of polyunsaturated fatty acids, Linoleic acid as well as Vitamin D (OR 0.6 in each case; 95% CI). The effect is stronger in women.
    (Case-control study; 674 participants over 3 years; Polesel J et al.; Linoleic acid, vitamin D and other nutrient intakes in the risk of non-Hodgkin lymphoma: an Italian case-control study; Ann Oncol 2006; 17: 713-718)
• selenium
  • The anti-leukemic effect of Selenite is linked to the inhibition of DNA replication, transcription, and translation.
    (Jiang XR et al.; The anti-leucaemic effects and the mechanism of sodium selenite; Leuk Res 1992; 16; 347-352)

Individual tumor types

A) Prostate

• Fish/Omega 3 fatty acids
  • Arachidonic acid and its metabolite prostaglandin E2 promote the migration of cancer cells, thus driving invasion into the bone marrow. Omega-3 fatty acids inhibit the migration of prostate cancer cells into the bone marrow when present at half the concentration of omega-6 fatty acids. Omega-3 fatty acids Eicosapentaenoic acid and docosahexaenoic acid can prevent prostate cancer cells from reaching the bone marrow.
    (Brown MD et al.; Promotion of prostatic metastatic migration towards human bone marrow stoma by Omega 6 and its inhibition by Omega 3 PUFAs; Br J Cancer 2006; 27; 94: 842-853)
  • No association can be found between Fishintake and prostate cancer, but (in studies with 49,641 participants) a significant reduction in prostate cancer-specific mortality (RR 0.37).
    (Meta-analysis (u.a. 12 case-control studies with 15,582 participants and 12 cohort studies with 445,820 participants); Szymanski KM et al.; Fish consumption and prostate cancer risk: a review and meta-analysis; Am J Clin Nutr 2010; 92: 1223-1233)
  • Prostate cancer: Fat content of food and Fat type have a significant influence on cancer cell growth: A fat-modified diet, in contrast to a high-fat Western diet, leads to a significant inhibition of prostate cancer cell growth.
    (Randomized, prospective; Aronson WJ et al. “growth inhibitory effects of a low fat diet on prostate cancer cells in vitro: results of a prospective randomized dietary intervention trial in men with prostate cancer”. AUA 2005, Abstr. 1417)
• Vitamin E
  • Prostate cancer: Mortality is significantly reduced by 41% with alpha-tocopherol (Vitamin E) 50 mg.
    (Randomized, double-blind; 29,133 smokers; Heinonen OP et al.; ATCB study; J Natl Cancer Inst 1998; 90; 440-446)
  • A long-term Vitamin ESupplementation of 400 IU and above is associated with a 57% reduction in the extent (locally invasive and/or metastatic) of existing prostate cancer (HR = 0.43; 95% CI).
    (Prospective cohort study; 35,242 participants; Peters U et al.; Vitamin E and selenium supplementation and risk of prostate cancer in the Vitamins and lifestyle (VITAL) study cohort; Cancer Causes Control 2008; 19: 75-87)
  • Prostate cancer: Vitamin E It suppresses the release of PSA and androgen receptors. Combined use of vitamin E and the antiandrogen flutamide significantly inhibits LNCaP cell growth. Selenomethionine also shows an inhibitory effect on LNCaP cell growth.
    (Yu Zhang et al.; Vitamin E succinate inhibits the function of androgen receptor and the expression of prostate-specific antigen in prostate cancer cells; Proc Natl Acad Sci USA 2002; 99; 7408-7413)
• soy
  • Soy isoflavonesSupplementation of 60 mg in the early stages of prostate cancer affects surrogate markers for cancer proliferation such as PSA and free testosterone.
    (76 participants over 12 weeks; Kumar NB et al.; The Specific Role of Isoflavones in Reducing Prostate Cancer Risk; The Prostate 2004; 59; 141-147)
• Broccoli (sulforaphane)
  • broccoli (or the ingredient) Sulforaphan) makes aggressive and resistant pancreatic cancer stem cells (pancreatic carcinomas contain approximately 10% of these cells) vulnerable and slows down metastasis of pancreatic cancer (in Germany, approximately 12,650 cases of pancreatic cancer occur each year).
    (Kallifatidis G, Herr I et al.; Sulforaphane targets pancreatic tumor-initiating cells by NF-kB-induced antiapoptotic signaling. GUT 2008, in press)
• selenium
  • Selenite It significantly increases p53 in prostate cancer cells. This is important for the activation of caspase-mediated apoptosis in cancer cells (involving the caspase-8 and caspase-9 pathways).
    (Jiang C et al.; Selenite-induced p53 Ser-15 phosphorylation and caspase-mediated apoptosis in LNCaP human prostate cancer cells; Mol Cancer Ther 2004; 3; 877-884)

B) Gynecological tumors

• Antioxidants
  • breast cancer and AntioxidantsThe levels of ROS, MDA, and antioxidant enzyme activities are significantly higher in breast cancer patients than in controls. The levels of vitamin C, GSH, GSSG (oxidized glutathione), and the GSH/GSSG ratio are significantly lower.
    (Yeh CC et al.; Superoxide anion radical, lipid peroxides and antioxidant status in the blood of patients with breast cancer; Clinica Chimica Acta 2005; 361; 104-111)
• Vitamin D
  • Women in the early stages of breast cancer have significantly higher vitamin D levels than women with advanced or metastatic breast cancer. Vitamin D It affects the regulation of the cell cycle and may delay tumor growth.
    (558 participants; Palmieri C et al.); Serum 25-hydroxyvitamin D levels in early and advanced breast cancer; J Clin Pathol 2006; 59; 1334-1336)
• Vitamin E
  • Cervical cancer and Vitamin E: Plasma levels of alpha-tocopherol and alpha-tocopheryl quinone (oxidized alpha-tocopherol) are significantly reduced in the study group compared to controls.
    (72 participants; Palan PR et al.; [alpha]-tocopherol and [alpha]-tocopheryl quinone levels in cervical intraepithelial neoplasia and cervical cancer; American Journal of Obstetrics && Gynecology. 2004; 190; 1407-1410)
• Resveratrol
  • Resveratrol Resveratrol induces S-phase arrest in human ovarian carcinoma Ovcar-3 cells via Tyr15 phosphorylation of Cdc2. Overexpression of Cdc2AF, a mutant resistant to Thr14 and Tyr15 phosphorylation, reduced resveratrol-induced S-phase arrest. Resveratrol causes phosphorylation of the cell division cycle 25C (CDC25C) tyrosine phosphatase via activation of checkpoint kinases Chk1 and Chk2, which in turn are activated by ATM (ataxia-telangiectasia mutant)/ATR (ataxia-telangiectasia Rad3-related) kinase in response to DNA damage. Resveratrol also increases phospho-H2A.X (Ser139), which is phosphorylated by ATM/ATR in response to DNA damage. The involvement of these molecules in resveratrol-induced S-phase has also been confirmed in studies showing that the addition of the ATM/ATR inhibitor caffeine reverses the resveratrol-mediated activation of ATM/ATR Chk1/2 as well as the phosphorylation of CDC25C, Cdc2, and H2A, and S-phase arrest. Resveratrol also induces S-phase arrest and the H2A.X- (Ser139) Phosphorylation in the ovarian cancer cell lines PA-1 and SKOV-3 (albeit at different levels), whereas in normal
    human foreskin fibroblasts with undetectable levels of phospho-H2A.X (Ser139) showed only marginal S-phase arrest. Resveratrol posits Cdc2-tyr15 phosphorylation via the ATM/ATR-Chk1/2-Cdc25C pathway as a central mechanism for DNA damage and S-phase arrest selectively in ovarian carcinoma cells and provides a rationale for the potential efficacy of ATM/ATRAgonians in cancer prevention and intervention.
    (Tyagi A et al.; Resveratrol causes Cdc2-tyr15 phosphorylation via ATM/ATR-Chk1/2-Cdc25C pathway as a central mechanism for S phase arrest in human ovarian carcinoma Ovcar-3 cells; Carcinogenesis 2005; 26: 1978-1987)
  • Resveratrol It has antineoplastic activity. It inhibits the growth and induces the death of ovarian carcinoma cells (more via autophagy than via apoptosis). u.a...associated with caspase activation. It therefore induces cell death via two different pathways: non-apoptotic and apoptotic (via release of the anti-apoptotic proteins Bcl-xL and Bcl-2).
    (Opipari AW et al.; Resveratrol-induced autophagocytosis in ovarian cancer cells; Cancer Research 2004; 64, 696-703)
• selenium
  • selenium is an important cofactor in the production of antioxidants Enzymen.Selen reduces the
    Cancer mortality in intervention studies. Selenium intake (in individuals with low selenium intake) prior to breast cancer diagnosis is inversely associated with breast cancer-specific mortality (HR 0.69) and overall mortality.
    (Harris HR et al.; Selenium intake and breast cancer mortality in a cohort of Swedish women. Breast Cancer Res Treat.2012; 134(3):1269-77)
  • Increased seleniumSelenium supplementation leads to a significant reduction in VEGF and intratumoral microvessel density in breast cancer. Selenium thus reduces angiogenesis.
    (Jiang C et al.; Selenium induced inhibition of angiogenesis in mammary cancer at chemopreventive levels of intake; Mol Carcinog 1999; 26; 213-225)

C) Gastrointestinal tract and pancreas

• Antioxidants
  • 5-FU has a response rate of only 20% in colorectal cancer, but remains the only most effective treatment. Antioxidants (such as vitamin E) induce apoptosis in CRC cells via the activation of p21 WAF1/CIP1, a potent cell cycle inhibitor (with the integration of C/EBPbeta, a member of the CCAAT enhancer-binding protein family of transcription factors) – independently of p53. Antioxidants Tumor growth inhibition is significantly increased by cytostatic therapy with 5-FU (and doxorubicin). The combination of chemotherapy and antioxidants provides a new therapy for CRC.
    (Chinery R et al.; Antioxidants enhance the cytotoxicity of chemotherapeutic agents in colorectal cancer: a p53-independent induction of p21 via C/EBP-beta; Nat Med 1997; 3; 1233-1241)
  • Supplementation of Vitamin C alone and in combination with Beta-carotene This leads to a lower number of advanced ductal lesions in rat pancreatic carcinomas. Vitamin E and/or selenium have no effect.
    (Appel MJ et al.; Lack of inhibitory effects of beta-carotene, vitamin C, vitamin E and selenium on development of ductular adenocarcinomas in exocrine pancreas of hamsters; Cancer Lett 1996; 103: 157-162)
  • Vitamin E significantly inhibits cell growth in human pancreatic carcinoma cell lines.
    (Heisler T et al.; Peptide YY augments gross inhibition by vitamin E succinate of human pancreatic cancer cell growth; J Surg Res 2000; 88: 23-25)
  • Treatment with Vitamin C, Vitamin E and Selenium significantly reduces deaths from stomach and esophageal cancer
    (Randomized, placebo-controlled; 3365 participants; Ma Jl et al.; Fifteen year effects of Helicbacter pylori, garlic, and vitamin treatments on gastric cancer incidence and mortality; J Natl Cancer Inst 2012; 104; 488-492)
• Vitamin D
  • Vitamin D In patients with colon cancer, it significantly reduced mortality for all causes of death (HR 0.52 for highest vs. lowest levels). For colon cancer mortality, the reduction was 39%.
    (304 participants (Nurses Health Study, Health Professionals Follow Up Study); Ng K et al.; Circulating 25-Hydroxyvitamin D Levels and Survival in Patients With Colorectal Cancer; Journal of Clinical Oncology 2008, 26, 2984-2991)
• Calcium
  • Colorectal adenomas: Under supplementation with Calcium (calcium carbonate or calcium gluconolactate) the number of adenoma recurrences was significantly lower than in the randomized comparison group (RR: 0.80, CI: 0.68, 0.93)
    (Meta-analysis of 3 studies with 1485 participants; Shaukat A et al.; Role of supplemental calcium in the recurrence of colorectal adenomas: a meta-analysis of randomized controlled trials; Am J Gastroenterol.2005; 100; 390-294)
• Alpha-lipoic acid
  • There is evidence that Alpha-lipoic acid or the reduced form dihydrolipoic acid effectively induces apoptosis in human HAT-29 colon cancer cells through a pro-oxidative (mitochondrial) mechanism.
    (Wenzel U et al:; alpha-Lipoic acid induces apoptosis in human colon cancer cells by increasing mitochondrial respiration with a concomitant O2-*-generation; Apoptosis 2005 Mar; 10(2):359-368)
• Lycopene
  • Lycopene It inhibits cell proliferation in human colon cancer cells and the activation of the phosphoinositide 2 kinase/Akt signaling pathway (regulates the survival of cancer cells).
    (Tang FY et al.; Lycopene inhibits growth of human colon cancer cells via suppression of the Akt signaling pathway; Mol Nutr Food Res 2008; 52; 646-654)
• Resveratrol
  • Resveratrol 25 micrometers reduced the growth of human colon cancer cells by 70%. The cells accumulated during the S/G2 phase transition of the cell cycle. Resveratrol significantly reduced the activity of ornithine decarboxylase (a key enzyme in polyamine biosynthesis, which is involved in cancer growth).
    (Schneider Y et al.; Anti-proliferative effect of resveratrol, a natural component of grapes and wine, on human colonic cancer cells. Cancer Lett. 2000; 158, 85-91)
  • Resveratrol 200 mcg/kg significantly reduces colon cancer carcinogenesis in rats. It significantly reduces cell count and alters the expression of bax and p21.
    (Tessitore L et al.; Resveratrol depresses the growth of colorectal aberrant crypt foci by affecting bax and p21 (CIP) expression. Carcinogenesis 2000; 21, 1619-1622)
  • Resveratrol 100 mcmol/l significantly inhibits cell growth in pancreatic carcinoma cell lines (PANC-1 and AsPC-1) in a concentration- and time-dependent manner and induces cell apoptosis.
    (Ding XZ et al.; Resveratrol inhibits proliferation and induces apoptosis in human pancreatic cancer cells; Pancreas 2002; 25: e71-76)
• Alcohol consumption (wine vs. other alcoholic beverages)
  • A dose-response relationship exists between alcohol and rectal cancer. More than 41 drinks per week resulted in a relative risk of rectal cancer of 2.2 (95% CI) compared to non-drinkers. More than 14 drinks of beer and spirits—but not wine—per week resulted in an RR of 3.5 for rectal cancer compared to non-drinkers, while those who consumed the same amount of alcohol, but with more than 30% of it being wine, had an RR of 1.8 for rectal cancer. No association was found between alcohol and colon cancer when examining the effects of the total amount of alcohol from beer, wine, and spirits, or the proportion of wine in total alcohol consumption. Alcohol consumption is associated with a significantly increased risk of rectal cancer, but the risk appears to be reduced when wine is included.
    (Randomized, population-based cohort study (Copenhagen, Danish Cancer Registry); 29,132 participants over 14.7 years; Pederson A, Johansen C, Groenbaek M; Relations between amount and type of alcohol and colon and rectal cancer in a Danish population based cohort study; Gut 2003;52:861-867)
  • Overall, the alcoholAlcohol consumption itself is not associated with stomach cancer, but the type of alcohol seems to influence the risk.Compared to non-wine drinkers, participants who drank 1-6 glasses of wine per week had a relative risk of 0.76 (95% CI), while those who drank more than 13 glasses of wine per week had an RR of 0.16 (95% CI). A significant association was found, with an RR of 0.60 (95% CI), for each glass of wine consumed per day. There was no association between beer or spirits and stomach cancer.
    (3 prospective population-based studies; 28463 participants; Barstad B, Groenbaek M et al.; Intake of wine, beer and spirits and risk of gastric cancer; European Journal of Cancer Prevention 2005; 14; 239-243)
• Broccoli (sulforaphane)
  • Treatment-resistant tumor stem cells play an important role in the pathogenesis of pancreatic cancer. Substances such as the broccoliingredient Sulforaphan They inhibit NF-κB, apoptosis inhibitors, and angiogenesis, and induce apoptosis. Combination with TRAIL (tumor necrosis factor-dependent apoptosis-inducing ligand) enhances apoptosis in tumor stem cells.
    (Kallifatidis G et al.; Sulforaphane targets pancreatic tumor-initiating cells by NF-kappaB-induced antiapoptotic signaling. Gut 2009; 58:949-63)
• Resveratrol
  • Resveratrol Resveratrol possesses a strong growth-inhibiting effect against various human cancer cells. Here, the inhibitory effect of resveratrol on experimental liver cancer is investigated using a two-stage rat model. Resveratrol (50-300 mg/kg body weight) reduces the incidence, number, volume, and diversity of visible hepatocyte nodules in a dose-dependent manner. It leads to a decrease in cell proliferation and an increase in apoptotic cells in the liver. It also induces the expression of the pro-apoptotic protein Bax, reduces the expression of the anti-apoptotic protein Bcl-2, and simultaneously increases the Bax/Bcl-2 ratio. Due to its favorable toxicity profile, resveratrol has the potential to be developed as a chemopreventive drug against human hepatocellular carcinoma.
    (Bishayee A, Dhir N; Resveratrol-mediated chemoprevention of diethylnitrosamine-initiated hepatocarcinogenesis: inhibition of cell proliferation and induction of apoptosis; Chem Biol Interact 2009; 179: 131-44)
  • Resveratrol HCT116 has a cancer-preventive effect and, at physiological doses, induces Bax-mediated and Bax-independent mitochondrial apoptosis in human colon carcinoma cells. Both pathways limit the cells' ability to form colonies.
    (Mahyar-Roemer M et al.; Role of Bax in resveratrol-induced apoptosis of colorectal carcinoma cells; BMC Cancer 2002; 2; 27-36)
• Quercetin
  • Quercetin It inhibits the growth of human stomach cancer cells. It affects DNA synthesis and cell progression from the G1 to the S phase of the Mitose.werden suppressed
    (Yoshida M et al.; The effect of quercetin on cell cycle progression and growth of human gastric cancer cells; FEBS Lett 1990; 260; 10-13)
• zinc
  • zinc inhibits the growth of pancreatic cancer cells more effectively than gemcitabine (the gold standard of chemotherapy).
    (Donadelli M etal.; Intracellular zinc increase inhibits p53(-/-) pancreatic adenocarcinoma cell growth by ROS/AIF-mediated apoptosis; Biochim Biophys Acta.2008)
• Omega 3 fatty acids
  • Polyunsaturated fatty acids (especially the Omega 3 fatty acid EPA) have a significant inhibitory effect on the growth of human pancreatic carcinoma cell lines.
    (Falconer JS et al.; Effect of eicosapentaenoic acid and other fatty acids on the growth in vitro of human pancreatic cancer cell lines; Br J Cancer 1994; 69: 826-832)

D) Hematology

• Vitamin K2
  • Myeloma cells and B-cell lymphomas (hematological neoplasms) are sensitive to Vitamin K2Growth inhibition occurs u.a. via apoptosis and activation of caspase-3. K2 represents a good treatment for myeloma patients, especially for those who are not suitable for intensive cell-reducing chemotherapy due to age or complications.
    (Tsujioka T et al; The mechanisms of vitamin K2-induced apoptosis of myeloma cells; Haematologica 2006; 91: 613-619)
• Vitamin D
  • Vitamin DVitamin D levels are seasonal. The time of year at diagnosis is also a strong prognostic factor for Hodgkin's lymphoma (a hematological neoplasm), with approximately 20% fewer fatal cases in autumn compared to winter (RR 0.783; 95% CI). Survival time is increased by more than 60% in patients under 30 years of age diagnosed in autumn (RR 0.364; 95% CI). Elevated vitamin D levels have a beneficial effect on conventional therapy.
    (Epidemiological study over 36 years; Porojnicu AC et al.; Season of diagnosis is a prognostic factor in Hodgkin's lymphoma: a possible role of suninduced vitamin D; Br J Cancer 2005; 93: 571-574)
• Magnesium and zinc
  • Children with acute lymphoblastic leukemia (ALL) and malignant lymphoma (hematological neoplasms) show reduced levels of [something] in their hair compared to controls. magnesium (significant only in T-cell ALL) as well as significantly reduced levels of zincSerum zinc levels are also reduced.
    (58 participants; Sahin G et al.; High prevalence of chronic magnesium deficiency in T cell lymphoblastic leukemia and chronic zinc deficiency in children with acute lymphoblastic leukemia and malignant lymphoma; Leuk Lymphoma 2000; 39: 555-562)
• selenium
  • In patients with aggressive B-cell non-Hodgkin lymphoma (hematological neoplasm) undergoing anthracycline-based chemotherapy and/or radiation therapy, serum levels correlate withseleniumMirror positive with response rate (OR 0.62; 95% CI) and long-term remission after initial treatment as well as overall survival (HR 0.76 for 0.2 mmol/l increase; 95% CI).
    (Last KW et al.; Presenting serum selenium predicts for overall survival, dose delivery, and first treatment response in aggressive non-Hodgkin's lymphoma; J Clin Oncol 2003; 15; 2: 2335-2341)
• Grape seed extract (OPC)
  • Through Grape seed extract (OPC) Apoptosis is induced in human leukemia cells in a dose- and time-dependent manner (via activation of c-Jun NH2-terminal kinase).
    (Gao N et al.; Induction of apoptosis in human leukemia cells by grape seed extract occurs via activation of c-Jun NH2-terminal kinase; Clinical Cancer Research 15, 140, January 1, 2009. doi: 10.1158/1078-0432.CCR-08-1447)
• Resveratrol
  • Resveratrol Induces survivin downregulation and apoptosis, as well as inhibition of cell growth in T-cell leukemia cell lines.
    (Hayashibara T et al.; Resveratrol induces downregulation in survivin expression and apoptosis in HTLV-1-infected cell lines: A prospective agent for adult T cell leukemia chemotherapy; Nutrition and cancer 2002, 44, 192-201)
  • Resveratrol It inhibits the growth of leukemia cells in cultures. It induces leukemia cell differentiation, apoptosis, cell cycle arrest in the S phase, and inhibition of DNA synthesis by blocking ribonucleotide reductase or DNA polymerase.
    (Tsan MF et al.; Anti-leukemia effect of resveratrol. Leuk. Lymphoma 2002; 43, 983-987)
  • Resveratrol 50 microM induces apoptosis in more than 80% of CD95-sensitive and CD95-resistant cells of acute lymphoblastic leukemia (ALL) by depolarization of mitochondrial membranes and activation of caspase-9, independent of CD95 signaling. No significant cytotoxicity to normal peripheral blood cells is observed.
    (Dorrie J et al.; Resveratrol induces extensive apoptosis by depolarizing mitochondrial membranes and activating caspase-9 in acute lymphoblastic leukemia cells. Cancer Res. 2001; 61, 4731-4739)
  • Resveratrol Resveratrol develops antiproliferative activity. It inhibits proliferation and induces cytotoxicity or apoptosis of cells in the malignant lymphoma Waldenström's macroglobulinemia (WM). Peripheral blood cells are not affected. Resveratrol exhibits synergistic cytotoxicity when combined with dexamethasone, fludarabine, and bortzomib.
    (Roccaro AM et al.; Resveratrol Exerts Antiproliferative Activity and Induces Apoptosis in Waldenstrom's Macroglobulinemia; Clin. Cancer Res 2008; 14: 1849 – 1858)
  • The aim of this study was to investigate interactions of Ellagic acid and Quercetin with Resveratrol (Polyphenols) have been shown to induce apoptosis and reduce cell growth in human leukemia cells (MOLT-4). The combination of ellagic acid and resveratrol exhibits more than additive synergistic effects. Both substances, individually and together, induce significant changes in cell cycle kinetics. Positive synergistic interactions exist between ellagic acid and resveratrol, as well as between quercetin and resveratrol, in the induction of caspase-3 activity. The anticancer potential of foods containing polyphenols can be enhanced through synergistic effects.
    (Mertens-Talcott SU, Percival SS; Ellagic acid and quercetin interact synergistically with resveratrol in the induction of apoptosis and cause translent cell cycle arrest in human lekemia cells; Cancer Lett 2005; 218; 141-151)

E) SKIN

• Vitamin C
  • Vitamin C Induces apoptosis of melanoma cells in vitro.
    (Kang JS et al.; Sodium ascorbate (vitamin C) induces apoptosis in melanoma cells via the down-regulation of transferrin receptor dependent iron uptake; J Cell Physiol 2005; 204: 192-197)
• Vitamin E
  • Vitamin E In vitro, it promotes quiescence and inhibits angiogenesis in melanoma cells. It also significantly suppresses the expression of VEGF (endothelial growth factor), VEGF receptor 1, and VEGF receptor 2 in melanomas.
    (Malafa MP et al.; Inhibition of angiogenesis and promotion of melanoma dormancy by vitamin E succinate; Ann Surg Oncol 2002; 9: 1023-1032)
• Vitamin D
  • Low Vitamin DElevated 25-OH-D levels are significantly associated with greater tumor thickness (according to Berslow) in malignant melanoma and advanced stage. 564 patients had elevated 25-OH-D levels. &< 20 ng/ml, 145 had levels of 20-30 ng/ml and only 55 had levels in the normal range of at least 30 ng/ml.
    (764 participants; Gambichler T et al.; Serum-25-hydroxyvitamin D serum levels in a large German cohort of patients with melanoma; Br J Dermatol 2013; 168; 625-628)
  • Polymorphisms of the vitamin D receptor gene are associated with susceptibility and prognosis regarding malignant melanoma (MM). The data suggest that the antiproliferative effect of vitamin D may be linked to susceptibility to and prognosis of malignant melanoma (MM). Calcitriol (1,25(OH)2D3), the ligand of VDR, has a protective effect against MM.
    (Case-control study; 424 participants; Hutchinson PE et al.; Vitamin D receptor polymorphisms are associated with altered prognosis in patients with malignant melanoma; Clin Cancer Res 2000; 6: 498-504)
• selenium
  • Reduced serum levels are found in malignant melanomas and cutaneous T-cell lymphomas (CTCL).seleniumLevels vary depending on the stage of the disease: they are significantly lower in tumor recurrences than in tumors without recurrence.
    (251 participants; Deffuant C et al.; Serum selenium in melanoma and epidermotropic cutaneous T-cell lymphoma; Acta Derm Venereol 1994; 74: 90-92)
  • Patients with malignant melanoma have significantly lower seleniummirrors (increasingly with severity) as control subjects.
    (101 participants; Reinhold U et al.; Serum selenium levels in patients with malignant melanoma; Acta Derm Venereol 1989; 69: 132-136)
• Resveratrol
  • Solar radiation encompasses a broad electromagnetic spectrum, including ultraviolet (UV) radiation, which is potentially harmful to normal cells, and ionizing radiation, which is therapeutically beneficial in destroying cancer cells. UV radiation is responsible for the majority of skin cancers, as well as precancerous lesions such as actinic keratosis. Chemoprevention of UV damage using non-toxic substances, particularly plant-based antioxidants, is one approach to preventing photodamage, including photocarcinogenesis. This article discusses the photoprotective effects of Resveratrol We discussed the effects of resveratrol on UVB exposure-mediated damage. Furthermore, we also discussed studies showing that resveratrol can enhance the therapeutic effect of ionizing radiation on cancer cells. Based on the literature, resveratrol may be useful for preventing UVB-mediated damage, including skin cancer, and for improving the efficacy of radiation therapies against hyperproliferative, precancerous, and neoplastic conditions.
    (Reagan-Shaw S et al.; Resveratrol imparts photoprotection of normal cells and enhances the efficacy of radiation therapy in cancer cells; Photochem Photobiol 2008; 84: 415-421)
  • Non-melanoma skin cancer is the most frequently diagnosed malignant disease in the United States. The primary cause is repeated exposure to ultraviolet (UV) radiation (especially the UV-B component, 290-320 nm) from the sun. Chemoprevention using naturally occurring substances is considered a new dimension in the management of neoplasms (including skin cancer).We have shown that resveratrol provides protection against acute UV-B-mediated cutaneous damage in SKH-1 hairless mice. Understanding this mechanism is important. We have already shown that Resveratrol Resveratrol has chemopreventive effects against a range of UV exposure-mediated alterations in the cki-cyclin-CDK network and the mitogen-activated protein kinase (MAPK) signaling pathway. In this study, the skin of SKH-1 nude mice was irradiated with UV-B on alternating days. Topical pretreatment with resveratrol resulted in a significant inhibition of UV-B exposure-mediated increases in cell proliferation (Ki-67 immunostaining), epidermal cyclooxygenase-2 and ornithine decarboxylase, established markers of tumor promotion, protein and messenger RNA levels of survivin, and survivin phosphorylation in the skin of the mice. Resveratrol pretreatment also led to a reversal of the UV-B-mediated decrease in Smac/DIABLO and an increase in UV-B-mediated induction of apoptosis in mouse skin. Overall, our study shows that resveratrol has chemopreventive effects against UV-B exposure-mediated damage in the skin of SKH-1 hairless mice via the inhibition of survivin and related events.
    (Aziz MH et al.; Prevention of ultraviolet-B radiation damage by resveratrol in mouse skin is mediated via modulation in surviving; Photochem Photobiol 2005; 81: 25-31)

Source: Dr. Udo Böhm, Handbook of Cancer, 2014