Although there is no 100% guarantee of avoiding breast cancer, some lifestyle principles can significantly reduce the risk of its occurrence and development. Same as other types of cancer. All preventive recommendations fundamentally boil down, in the end, to just two *:
A. Getting rid of those risk factors that can be eliminated.
B. Compensation for those risk factors that cannot be changed.
Environmental measures include blocking the entry of carcinogens, their direct neutralization, as well as the neutralization of their action. Try to get rid of external carcinogenic toxins as much as possible, including cigarette and car smoke, alcohol, asbestos, xenoestrogens, untested cosmetics and household chemicals, etc. Get rid of aluminum in the kitchen and lead in dental fillings.
Meals † should be low-calorie, but complete, i.e. rich in essential and bioactive substances such as vitamins, minerals, fiber and bioflavonoids. Try to eat what you have grown and prepared yourself, and not bought from someone else. This makes it easier to control the quality and composition of the finished food. The composition of the food should be slightly alkaline-forming, not acid-forming.
Children can reduce their risk of breast cancer later in life by reducing fat and dairy products in their diet as much as possible. For people of any age, weekly one-two-day posts will be useful.
Supplements † for healthy young adults are not necessary if all other recommendations, especially diet, are followed. However, for people aged 40 and over, some supplements may be helpful.
The hormonal profile † must be balanced, even if hormone levels are low due to age. Work and rest, activity and sleep should coincide with the natural circadian cycle.
Anti-inflammatory measures † include increasing antioxidant enzyme levels, neutralizing free radicals (natural polyphenols, vitamins C and E, other antioxidants), and inhibiting arachidonic acid metabolism (glycyrrhetinic acid, N-acetylcysteine, NSAIDs, plant polyphenols).
Immunity †. Maintaining an adequate immune response of the body (NSAIDs, selenium, vitamin E).
Normalization of body weight † helps reduce the risk of almost all diseases. An increase in body mass index for every 5 kg/m2 before diagnosis is associated with a 17% increased risk of all-cause mortality and an 18% increase in breast cancer mortality *.
Physical and social activity, a rhythmic circadian rhythm, adequate sleep increase the level of vitality.
Spiritual practices. Breathe life deeply. Every moment is unique, fill it with joy, not fuss. Live here and now. We have been given life for great things, not for petty squabbles. Hasten to fulfill your destiny. Think about Eternity, not about yourself. Look up at the heaven, not at your feet. Love others as the Lord loves you.
Diagnosis does not prevent disease. However, earlier detection of the tumor increases the effectiveness of treatment and improves the prognosis. But much more important is not so much the discovery of the tumor itself, but the discovery of its causes. Eliminating the causes will lead to the further disappearance of the problem itself. Keep under control all the main indicators of health – from blood acidity to inflammatory markers.
Everyone who wants to be healthy should monitor their key indicators listed in the «Benchmarks» section †.
Self-exams are not currently believed to reduce the risk of getting breast cancer, dying from breast cancer, or finding tumors at an earlier stage. However, it may be useful for women to know how to properly monitor the condition of the breast, first of all, external examination and palpation. Self-exam is advised to carry it out on the 5th-6th day from the beginning of the menstrual cycle, when the mammary gland is in a relaxed state, and in postmenopause – on the any day of the month. Cleveland Clinic offers the following procedure for self-examination *.
I. The first stage of the check is an external examination of the breast.
1. Stand naked to the waist in front of a large mirror in a well-lit room. Look at your breast. Don't be alarmed if they seem uneven in size or shape; no breasts are the same. With your arms relaxed at your sides, notice any changes in the size, shape, texture, or skin of your breasts. Look for any sores, any wrinkles, dimples, or skin discoloration. Examine your nipples and look for sores, peeling, or changes in the nipple area.
2. Then place your hands on your hips and press firmly to tighten your pectoral muscles under your breasts. Turn from side to side to inspect the breast from the outside.
3. Lean forward towards the mirror. Pull your shoulders and elbows forward to tighten your chest muscles. Your breast will drop forward. Look for any changes in the shape or contour of your breasts.
4. Now put your hands behind your head and stretch your arms forward. Once again, turning from side to side, examine the outer parts of your breast. Don't forget to examine the border under your breasts. You may need to raise your breast with your hand to see this area.
5. Check nipples for fluid.
Place your thumb and forefinger on the tissue surrounding the nipple and pull outward towards the end of the nipple.
Look for any highlights. Repeat the procedure on the other breast.
II. The second stage of the check is palpation.
6. To feel lumps, use the sensitive pads of the middle three fingers of your left hand, not your fingertips. It's good if your fingers are slippery from soap and water.
7. Check both breasts for lumps or thickening under the collarbone. Gently pressing with the pads of your fingers, in a circular, rubbing motion, feel the breast, looking for lumps. Check for lumps or lumps in the underarm area. Place your left hand on your thigh and extend your right arm to feel your left armpit. Repeat the procedure on the other side.
8. Support the breast with one hand while using your other soapy hand to feel the fabric. Use the flat part of your fingers to gently press down on your breast. Follow the picture along the breast up and down, moving from the bra line to the collarbone. Continue until you have covered the entire breast. Repeat the procedure on the other side.
9. Then lie down and place a small pillow or folded towel under your right shoulder. Place your right hand behind your head. Place your left hand on top of your right breast with your fingers folded and flat. Explore the right breast with the left hand. Body lotion may help relieve palpation. Press hard enough to feel the various breast tissues using the following three different techniques. First, light pressure to simply move the skin without pushing the tissue below it, then medium pressure – halfway into the tissue, and finally, to probe deeper into the ribs – deep pressure, until a moment a little less than discomfort.
10. Imagine your breast as a scoreboard on the clock face. In coin-sized increments, without lifting your fingers, start at the outermost edge of your breast and work your way in a spiral to the nipple.
Start at 12 o'clock and move towards 1 o'clock in small circles. Continue around the circle until you reach 12 o'clock again. Keep your fingers flat and in constant contact with your breast. When the circle is complete, move a couple of inches towards the nipple and complete the next full circle, and so on, until your entire breast is palpated. Be sure to palpate the upper outer areas that extend into your armpit.
11. Fully palpate the entire breast and breast area under the arm, up to the collarbone and all the way to the shoulder, to cover the outer part of the mammary gland extending in this direction. Place your fingers straight on the nipple. Look for any changes under your nipple. Gently push the nipple inward. He should move easily. Repeat steps 9, 10 and 11 on the other breast.
If you find any of the changes described below, you should consult a doctor.
• An area that is markedly different from any other area on any breast.
• A lump or swelling in or under or near the breast that persists through the menstrual cycle.
• Change in the size, shape or contour of the breast or the condition of the nipple.
• Feels like a pea-sized mass or lump.
• «Marble» area under the skin.
• Change in the appearance of the breast or the appearance of the skin on the breast or nipple (dimpled, wrinkled, scaly or inflamed – red, warm or swollen).
• Bloody or clear discharge from the nipple, which can also be seen on underwear.
• Redness of the skin on the breast or nipple.
The appearance of any seals in the breast indicates its trouble. More than 80% of the lumps are not cancerous, however, you should be sure of this in order not to miss the moment of the formation of a cancerous tumor.
Women between 20 and 40 years of age are advised to have an ultrasound scan every year, and women over 40 years of age – a mammogram every two years, if any pathologies are absent (there is controversy about the need and frequency of mammography!). If there are any pathologies, then during the first two years after its discovery, an examination by a specialist is carried out twice a year.
All preventive examinations of the breast are recommended to be carried out in the first phase of the cycle, starting from the 5th day, but not later than the 12th day of the cycle. During these first days, the breast tissue is the least sensitive to the effects of extraneous factors.
Lifestyle. Although early diagnosis helps to detect a tumor earlier, it cannot reduce the risk of cancer. Salvation is not a diagnostics, but prevention, a healthy lifestyle, a responsible attitude towards your body. The rules of a healthy lifestyle should be built into a habit. Follow the rules outlined in the «Strengthening Vitality» section †.
It is equally important to know which essential substances and minerals are deficient in the body, so that you can compensate for them by correcting the nutritional structure, and in case of failure, by taking appropriate supplements.
Nearly a quarter of breast cancer cases are diagnosed before the age of 50 *. From the moment of the onset of a cancerous tumor to its detection, an average of 16 years passes, and from the moment of diagnosing precancerous diseases to the cancer itself, about 10 years *. A growing body of work suggests that disease risks begin to accumulate from an early age, especially during puberty, when a woman's breast tissue is most sensitive. Therefore, prevention of breast cancer should start at a very early age *.
Most of the seals found on palpation are not tumors. However, this is evidence of a breast health problem that needs to be corrected. Do not panic, but you should take the problem that has appeared seriously. What looks like a petty misunderstanding today may turn into a tragedy tomorrow.
If a tumor is detected at an early stage, the probability of cure can approach 100%. This is especially true for luminal subtypes of cancer. But the time factor works against the patient. At first, a person, not realizing the seriousness of the symptoms, or not wanting to think about the bad, may not see a doctor for a long time and hope that everything will go away on its own. Then, having lost hope, he comes to the therapist; therapist refers him to a specialist; specialist – for additional examination. Finally, the diagnosis receives a serious suspicion of a tumor, and the patient receives a referral to an oncology clinic. Each of these steps takes a certain amount of time.
The oncologist must study the state of affairs, obtain the results of specialized studies, draw up a treatment plan; this also takes time. There will be some waiting time for the operation. The necessary chemotherapy drugs may not be available at the moment, and they, too, may have to wait for some time. But the tumor will not wait.
Fortunately, most breast tumors grow slowly. Sometimes so slowly that observation may be ordered instead of treatment. However, in the case of an advanced or aggressive tumor, two to three months without treatment can be critical. Each week of illness increases the size of the tumor. Every day increases the risk of metastasis. An invasive tumor invades further and further into neighboring tissues. Because of this, treatment becomes more difficult and traumatic, and the prognosis becomes less and less favorable.
Delaying treatment by 3 months can reduce the 5-year survival of a patient with a breast tumor by 12%, and a delay of 6 months by 19% *. Therefore, the first advice: do not start the disease. At the first symptoms, hurry up with the examination.
Take the diagnostic findings calmly, but responsibly. The only person who really cares about your health is you. You can not make fateful decisions based on fear, on myths, on false beliefs, experience and pressure from strangers. If you take the matter seriously, then you should study everything related to a personal problem in as much detail as possible until a reasonable conscious conclusion ripens. But, unfortunately, for a person who is in time trouble and does not have sufficient knowledge, this is difficult to implement. He remains to rely not on knowledge, but on faith.
Of course, a specialist knows his business better than an amateur. However, one should not blindly trust a single specialist. It will always be useful to listen to alternative opinions of specialists from other clinics. They often don't match. It is always worth going through repeated and/or additional tests and examinations. Because they can sometimes give opposite or even false conclusions. And lead to an unsuccessful choice of action plan. The more examination results and expert conclusions a specialist has in his hands, the more fully he represents the current picture of the disease. The more correct decision he can make.
Although the doctor has more knowledge and experience, he is limited in his freedom to choose treatment methods. In addition, he has neither the time nor the interest to lecture the patient or warn him of the negative consequences of his proposed treatment program. But the patient, before agreeing with the solution of the problem proposed by the doctor, wants to carefully understand whether it works with this subtype of cancer, and with what success. What side effects and consequences will it lead to. What suffering and deprivation to go through. What losses will he have to deal with? What exactly will he have as a result, what can he hope for, and what not.
If you completely transfer responsibility for your health to another person, then, if possible, choose a clinic and an oncologist whose experience and qualifications you absolutely trust. Who would be ready to speak frankly with you and spare no time for this. No matter how difficult it may be due to the high workload of the doctor, try to establish constructive work with him, because the result of treatment depends on your cooperation. Discuss with him not only the treatment protocol, but also any additional measures that you intend to implement.
And never give up. Cancer is treatable, which means treatment can give you several years of life. God forbid, so many years that they will last until old age.
From the moment of diagnosis to the moment of initiation of antitumor therapy, there may be a time gap that should not be given to the disease.
• A low-calorie diet, especially a diet high in whole grains, vegetables, fruits, nuts, and olive oil and low in saturated fats, omega-6 fats, and red meat, may improve overall survival after a breast cancer diagnosis *.
• Physical activity. Moderate levels of physical activity are associated with significantly lower overall and post-diagnosed breast cancer mortality * * * * and a reduced risk of recurrence in patients with ER–/PR–-tumors *.
The MET value is used to determine the activity intensity. Three units of MET is equivalent to walking at an average pace of 3.5-4 km/h for 1 hour. According to these calculations, 4 hours of daily walking at an average pace can halve the relative risk of death from cancer, especially in women with hormone-sensitive breast tumors. Compared to less than 3 MET/week of physical activity, an activity level of 3-9 MET/week reduces the relative risk of death from breast cancer by 20-35%, and an activity level of more than 9 MET/week by 40-50% * *.
• Social activity is also associated with lower overall mortality after breast cancer diagnosis *. However, this indicator strongly depends on the psychological component of communication, and is expressed in cases where activity brings positive emotions, a sense of one's importance and satisfaction from one's own need for people *.
Although physicians may not approve of the following suggestions, they are still worth discussing with them. Most likely, they will not mind, because they consider these measures insignificant.
• Anti-inflammatory drugs – aspirin (100-200 mg/day).
• Proteolytic enzymes – trypsin, chymotrypsin (400-1'200 mg/day), serrapeptase, nattokinase, bromelain and papain.
• Iodine (5 mg/day), selenium (200-400 μg/day).
• Vitamin D3 (in winter – 4'000 IU/day, i.e. 100 μg/day; in summer – 2'000 IU/day, i.e. 50 μg/day).
• Vitamin C. A special meta-analysis showed that dietary intake of 100 mg/day of vitamin C from the day of diagnosis reduced overall mortality by 27% and breast cancer mortality by 22% *.
• Antifibrotic agents – proanthocyanidins (300 mg/day), betaine (175 mg/day), myo-inositol (200 mg/day), boswellic acid (15 mg/day).
• An aqueous extract of Mistletoe (Viscum album) has shown high efficiency in combating breast cancer tumors, in some cases even causing its regression *. Unfortunately, the dosage of the standardized therapeutic agent was not specified in this study.
• Green tea. Tea consumption (about 100 g of dried tea leaves per month) during the first 60 months after cancer diagnosis was associated with improved survival in women with triple negative breast cancer *.
• Metformin. Women with invasive breast cancer who received metformin (500 mg/day for 1 week before surgery and then 2×1'000 mg/day for 1 week after surgery) showed a 3% reduction in a cell proliferation marker Ki67, while in the control group there was a 2% increase *. In another clinical study, women who took 1'700 mg/day of metformin for 4 weeks while awaiting surgery for breast cancer had a 12% reduction in HER2-positive ductal carcinoma cell proliferation markers compared to controls *.
• Extracts of garlic and lemon. Daily biweekly intragastric administration of 33% aqueous garlic extract (50 mg/kg) to mice with grafted mammary tumors was associated with a reduction in tumor size by 87% of its initial size. A similar treatment with whole lemon extract (50 mg/kg) was associated with an 83% reduction in tumor size. And the combination of both extracts was associated with a 92% reduction in tumor size, while in the control group, the tumor, on the contrary, increased by an average of 5.7 times *. In human terms, this dosage will be about 300 ml of extract, which looks too much.
Of course, it would be too naive to hope that the results of this single study in mice can give the same result in every cancer patient. In addition, achieving a noticeable result will take a long time. One day of a mouse's life is equivalent to about 40 days of a human's life; and 14 days of therapy in mice corresponds to about 1.5 human years. However, this example shows that a tumor can be successfully controlled.
Brochures have been produced to help women diagnosed with cancer, respectively for non-invasive *, invasive * and metastatic * cancers.
Is surgical removal of the tumor really necessary? As a rule, yes, but it all depends on the specific case. Removal of the main mass of the tumor reduces the tumor burden on the body and gives a chance for complete elimination of the tumor. However, in rare cases, surgery can be more dangerous than the tumor itself. For example, if the patient, for reasons of general health, cannot withstand it, or if the tumor is located in such a way that its removal could create a mortal risk.
In the case when the tumor does not grow, or grows very slowly, if it is local, small in size, does not interfere with the passage of blood, lymph, bile, food, etc., does not compress the nerves and vital centers, if the internal organs and the immune system is in order, and if there is hope to deal with it in a different way, then perhaps there is no need to rush into the operation *. Only a specialist can assess all the risks and make the right decision based on the results of the survey.
Surgery is always risky and stressful. In addition to incision, disruption of local blood flow, damage to underlying tissues, and activation of local inflammation, mechanical injury also causes systemic neuroendocrine and metabolic changes that can affect blood flow, coagulation, and immune function throughout the body.
Preparation. All recommendations of the surgeon in preparation for surgery should be followed.
Preparation will be more successful if you tell your doctor about the following possible circumstances:
- taking medication or other blood thinner;
- taking other medicines prescribed by a doctor or taken independently;
- taking supplements such as vitamins, minerals, and natural or home remedies;
- the presence of a pacemaker or other device for the work of the heart;
- the presence of allergies or intolerance to drugs or painkillers;
- past problems with anesthesia, other surgeries or blood transfusions;
- the presence of sleep apnea;
- smoking, drinking alcohol or light drugs.
Seven days before surgery, you should stop taking any supplements. You should also stop taking any drugs that prevent platelet aggregation (clumping): inositol, aspirin, turmeric, ginger, ginkgo, reishi, garlic, vitamin E, acetyl-L-carnitine, proteolytic enzymes, and other anticoagulants, as well as calcium, so as not to increase the risk of bleeding after surgery.
Such drugs, such as St. John's wort and valerian root, should be discontinued because they can prolong the effect of anesthesia.
Fasting at night and in the morning before surgery may be helpful *.
Immediately before the operation, the hearing aid, dentures and other prostheses, wig and the like should be removed, if any. Any metal objects, including jewelry and piercings, should also be removed because the equipment used during some operations may cause burns if it comes into contact with metal.
During your period, it will be better to use a sanitary napkin rather than a tampon.
Increased apoptosis of cancer cells.
In premenopausal women, breast surgery performed in the second half of the menstrual month (luteal phase), when progesterone levels are highest, is associated with higher patient survival * *.
Some supplements may be helpful:
• Progesterone is a hormone that enhances the apoptosis of estrogen-sensitive breast cancer cells. While topical application of estradiol to the breast 12 days before surgery leads to an increase in cell proliferation up to 62%, the use of progesterone reduces it to 72% compared with placebo control *.
Genomic research has revealed that progesterone favorably modulates several dozen genes that control the inflammatory response. The study suggested that preoperative exposure to progesterone may be beneficial in alleviating surgical stress *.
Patients with preoperative blood progesterone concentrations above 4 ng/mL had twice the 18-year survival rate compared to those with levels below 4 ng/mL (65% versus 35%) *. Approximately 2 weeks of preoperative topical application of progesterone in the form of a cream or gel is required to achieve the desired level of progesterone in the breast tissue, however, injections (500 mg of hydroxyprogesterone) also have beneficial effects on the surgical process *.
Progesterone also slightly reduces thrombosis *, reducing the risk of postoperative thromboembolism.
• Iodine also enhances apoptosis of cancer cells. Supplementation of 5 mg/day I2 for 7-35 days before surgery and 170 days after it (throughout chemotherapy) shows a significant reduction in the side effects of treatment, the absence of tumor chemoresistance, a decrease in its invasive potential, an exacerbation of the sensitivity of the estrogen receptor, as well as an increase in body's immune response and increased 5-year relapse-free survival *.
• Doxycycline (2×100 mg/day) taken orally 14 days before surgery to remove early breast cancer (ER–, ER+ and HER2+) significantly reduced stem cancer cell tumor markers (CD44 and ALDH1) in 90% of patients *.
Reducing the risk of metastasis. Any physical impact on the tumor, be it surgery, a biopsy, or even just a massage, can increase the number of circulating tumor cells in the blood.
The operation is the most critical period for the formation of metastases. Removing the primary tumor does not guarantee complete elimination of cancer cells. In this case, the surgical intervention breaks the integrity of the basement membrane surrounding the cancer cells, which allows potentially remaining cancer cells to escape unhindered beyond the fence. In addition, surgical stress promotes the growth of pre-existing micrometastases as well as small residual tumors in the postoperative period *.
Because metastatic disease is more dangerous than the original tumor, prophylactic measures should be taken during the operative period to prevent metastasis *.
• Modified citrus pectin (15 g/day) by binding to adhesion molecules galectin-3 on the surface of cancer cells * can effectively counteract the increase in adhesion of circulating cancer cells caused by surgery * *. Reducing the ability of cancer cells to bind to the walls of blood vessels is extremely important, given that surgery can increase it by 250% *.
• Cimetidine, commonly used for heartburn (800 mg/day), weakens cancer cell adhesion by blocking the expression of another adhesion molecule, E-selectin * *. Its use as an adjunct to standard therapy can prevent local tumor invasion and metastasis.
Colon cancer patients taking cimetidine immediately after surgery, and for up to one year after surgery, significantly increase the 10-year survival * *. In addition, taking cimetidine resulted in a 47% improvement in overall survival in these patients compared to those who did not *.
Patients with gastric cancer who took cimetidine (800 mg/day) showed a survival rate one and a half times higher than those who did not take it *. Cimetidine helps counteract the decline in T-cells, T-helpers and NK cells *. However, an association between preoperative cimetidine and altered tumor cell proliferation in breast cancer has not yet been identified *.
• Desloratadine or meclizine may be preferred over cimetidine as there is no suspicion of estrogenic activity *. Any of these three substances in combination with modified pectin can be taken one week before surgery and continued for up to a year after it.
• Diclofenac (75 mg/day) or ketorolac (20-30 mg/day)taken during and after surgery, due to COX2/PGE2 inhibition, may be associated with a lower risk of cancer recurrence or metastasis after surgical removal of tumors *.
• Propranolol given during surgery, by reducing beta-adrenergic signaling and slightly improving immune response, may also be associated with a reduction in metastases *. The combination of propranolol and COX2 inhibitors may have a synergistic effect in reducing systemic inflammation * *. Etodolac (400 mg/day) can be used as a COX2 inhibitor; and propranolol is taken at the following dosage: 20 mg/day for 5 days before surgery and 5 days after it, and 80 mg slowly administered on the day of surgery.
• Removal of dead teeth and periodontal healing before surgery. Periodontal inflammation promotes metastasis of breast cancer to the head and neck *.
Decreased postoperative inflammation. Traumatic intervention always causes an acute inflammatory process. On the one hand, inadequately completed, chronic inflammation can contribute to the development of a tumor. On the other hand, a strong surge of inflammatory signals in the tumor area can restart the confused and contradictory picture of the inflammatory process that is the tumor. Thus, we should take advantage of the chance presented by the operation so that the postoperative inflammation passes in the normal mode, synchronizes all local processes of tissue repair and extinguishes potentially remaining inflammatory foci of the removed tumor.
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin (100 mg/day) may reduce the number of circulating cancer cells with long-term use *, but the use of aspirin during surgery is generally not recommended. Currently, there are more modern NSAIDs such as amtolmetin guacil (600-1'200 mg/day) and licofelone. Long-term use of COX-2 inhibitors such as celecoxib can dramatically reduce the risk of bone metastases in stage II-III breast cancer *.
A 5-year follow-up clinical trial of celecoxib (REAC), based on a subgroup analysis of primary breast cancer, showed that patients who took celecoxib after surgery (400 mg/day) almost halved the number of non-cancer-related deaths *.
Patients treated with ketorolac (30 mg/day) before and during surgery improved disease-free survival by up to 43% *, and reduced the number of early relapses by up to 41% compared with patients not taking ketorolac *. Given such high rates, it is difficult to resist not recommending ketorolac or celecosib during surgery. There is a natural concern that taking NSAIDs such as ketorolac may increase the risk of postoperative bleeding. However, a meta-analysis of 27 studies showed that it was practically not increased in the ketorolac group compared to the control group, and side effects were not statistically different between groups *.
Clarithromycin (2×500mg) has also been reported to improve inflammatory responses after breast removal by normalizing temperature, heart rate and respiration, and reducing the intensity and duration of pain compared to controls *.
Some effective and affordable natural anti-inflammatory supplements include:
• Coenzyme Q10 (CoQ10) increases the number and activity of macrophages and T-lymphocytes *.
• A combination of magnesium (2×50mg), zinc (2×2mg), calcium (2×200mg), and vitamin D3 (2×100IU) taken for 12 weeks can significantly reduce C-reactive protein *.
• Vitamins В8 (1-2 g/day), C (100 mg/day), E (15 mg/day), D3 (4'000 IU/day), alpha-lipoic acid (100-200 mg/day) and glutathione (100 mg/day) also markedly reduced levels of the inflammatory marker C-reactive protein in patients.
• In two clinical trials, patients who received post-surgery injections of escin, a horse chestnut extract (5-10 mg twice a day), noticed a decrease in temperature and swelling 3-4 days after surgery * *.
• Bromelain has shown anti-inflammatory effects in a double-blind, crossover study in surgically treated patients *. A typical oral dose of bromelain is 3×250-750 mg on an empty stomach.
Inflammation is accompanied by a peripheral increase in oxidative damage to membrane lipids. Thus, before surgery, antioxidant supplements may be useful *: curcumin, EGCG, resveratrol, vitamins С, Е, D. Curcumin, despite its high efficiency, has poor bioavailability, but the addition of piperine in a ratio of 10:1 significantly increases it. Phytosomal and liposomal curcumin are also biologically highly available. In some studies, melatonin also reduced oxidative cell damage caused by surgery * (60 mg melatonin intravenously during surgery and 10 mg orally for three nights after surgery *).
Oxygen *, vitamins (A, C, E) *, minerals, amino acids and fatty acids * are required for an optimal wound healing process and with it a reduction in proliferation. It would be logical to assume that an adequate supply of this and other materials (glucosamine, bromelain, etc.) * will contribute to the healing of a stubbornly non-healing wound that the body sees in a tumor. For example, in one 9-week clinical study, a complex containing protein (46 g/day), arginine (6.9 g/day), vitamin C (575 mg/day), vitamin E (87 mg/day), and zinc (21 mg/day), improved the healing of chronic wounds *.
Reducing the risk of postoperative
If the skin around the incision becomes very red or red, or if there is a discharge that looks like pus, these symptoms should be reported to the doctor.
Іmmune support. Surgery and anesthesia also entail a weakening of immune functions * *. For example, in women who have had surgery for breast cancer, NK (natural killer) cell activity on the first day after surgery can be more than halved *. This, unfortunately, happens just at the moment when they are most in demand.
• Beta-glucan is a long-chain polymer of carbohydrates, one of the most studied immunomodulators of both innate and adaptive immunity * * * *. In particular, the enzymatically modified rice bran extract activates NK (natural killer) cells, T cells, macrophages and monocytes * * *. Beta-glucans extracted from mushrooms such as Turkey tail (Trametes versicolor), Chaga (Inonotus obliquus), Shiitake (Lentinus edodes), Reishi aka Lynchshi (Ganoderma Lucidum) also increase NK cell activity *.
Just 20 mg of beta-glucan per day for 10 days significantly accelerates the healing of postoperative injuries and the number of days required to remove the drain in patients after mastectomy *. Long-term use of beta-glucan (7.5 mg/day for 15 months) after surgery can significantly reduce the risk of breast cancer recurrence. And taking 15 mg/day significantly prolongs life in inoperable patients *.
A rich source of beta-glucan is cereal shells (bran) and brewer's yeast. Another multipurpose natural remedy containing beta-glucans is Cordyceps (Cordyceps sinensis)* (30 ml/day or 3 g before surgery and 10 ml/day or 1.5 g/day for 2-8 weeks after surgery).
• Naltrexone markedly attenuates surgery-induced immune suppression *, but this opioid is expensive and requires a prescription.
• Selenium, germanium, aged garlic *, berberine *, IP6 (inositol hexaphosphate) * and lactoferrin * can be used to increase NK cell activity. The addition of glutamine to rats (1 g per 1 kg of feed) increased the activity of NK cells by 2.5 times and reduced the growth of transplanted mammary tumors in them by 40% *.
• Mistletoe extract (Iscador™) intravenously just before general anesthesia completely reverses the reduction in NK cell activity caused by surgery *.
• Echinacea purpurea (Echinacin®) taken orally can increase NK cell activity by 25% * and phagocyte activity by 120% *, but its effectiveness disappears after 1-2 weeks of use *. Combining echinacea with melatonin enhances the effects of echinacea *.
• Giloy (Tinospora cordifolia) orally (1'200 mg/day) can significantly improve postoperative status by normalizing neutrophil function *. Other herbal adaptogens: Leuzea carthamoides, Baikal skullcap, Rhodiola rosea, Ginseng, Aralia elata. All herbal adaptogens are taken for at least 10 days, and 3 days before surgery, they should be stopped.
• Melatonin *,
sulindac (equiv. 400 mg/day) *
and interferon-gamma *
reduce the ratio of protumor M1 macrophages to antitumor M2 macrophages in tumors in favor of the latter.
The combination of melatonin (20 mg) with Aloe Vera (Aloe vera) shows a synergistic effect and is able to stabilize the condition in half of cancer patients *. In the latter case, aloe leaves were crushed and mixed with a preservative (vodka) in a ratio of 1:9, after which the tincture was taken 1 ml in the morning and evening daily.
Due to the operation, the patient is prescribed anesthesia and antibiotics, which can destroy the beneficial intestinal microflora, weakening the support of the colon's immune cells and reducing the body's natural resistance to the formation of metastases. Maintaining a healthy bacterial composition of the intestine has a beneficial effect on the immune state of the patient.
• Probiotics, mainly lactobacillus and bifidobacteria (Lactobacillus acidophilus, Lactobacillus plantarum, Bifidobacterium lactis and Saccharomyces boulardii), can reduce the incidence of all serious postoperative complications (28.6% vs. 48.8%), including postoperative pneumonia (2.4% vs. 11.3%) and postoperative infection (7.1% vs. 20.0%) *.
Suppression of angiogenesis. he operation enhances angiogenesis (the formation of new blood vessels), which promotes wound healing. However, an increase in the level of angiogenic factors also contributes to tumor recurrence and increased growth activity of dormant micrometastases *. In addition, the primary tumor produces anti-angiogenic factors that limit the growth of metastatic cancer in other parts of the body * *, and its surgical removal removes the restriction on the growth of micrometastases *.
Some supplements can reduce the intensity of angiogenesis: zinc; EGCG from green tea (1 g/day) *; curcumin (up to 4 g/day) *; grape seed proanthocyanidins (20 μg/mL) *; ellagic acid from pomegranate fruits and seeds (200 mg/day, or from 250 ml/day of pomegranate juice) *. The combination of ellagic acid with phosphatidylcholine in a 1:4 ratio can double its bioavailability *.
Tissue restoration. Postoperative repair of damaged tissue may be accompanied by the formation of scars, adhesions, and insufficiently functional architecture. Started as early as possible, the gradual restoration of physical activity improves the healing process of injured tissues. For this, the medical staff can offer various physical exercises. Postoperative pain, sensitivity, numbness and stiffness must be overcome.
• Gotu kola (Centella asiatica), aka Centella. The leaf extract of the plant prevents the formation of postoperative adhesions and reduces postoperative scars * *. Dosage: 3×200 mg dried leaves per day. Can be brewed as a tea: 1-2 teaspoons (5-10 g) of leaves per 1 cup of boiling water, let steep for 10-15 minutes *.
• Serrapeptase (serratiopeptidase, Serrata™) is a proteolytic enzyme that has an anti-inflammatory effect, reduces postoperative tissue swelling, improves microcirculation and promotes recovery processes. In a clinical study, patients received 3×10 mg/day of serrapeptase before surgery, once the night after surgery, and 3×10 mg/day for 5 days after surgery *. However, in the presence of an abscess, its use is contraindicated, since the dissolution of the fibrin membrane may contribute to the spread of the abscess. In addition, serrapeptase increases blood fluidity, so it can greatly increase the effect of other fibrinolytic agents such as aspirin, warfarin, ginkgo biloba.
Complexes trypsin+chemotrypsin (Chymoral Forte® 100'000 E) and trypsin+bromelain (48 mg + 90 mg) showed a better postoperative anti-inflammatory effect compared to serrapeptase *.
• Intravenous administration of Sage extract (Salvia miltiorrhiza) on the day of surgery and for 3 days after it allowed to reduce ischemia and necrosis of skin flaps after breast removal as effectively as anisodamine, but without the side effects of the latter *. However, the dosage used in this clinical study was not specified.
Red Light Therapy is a safe and effective means of relieving postoperative pain when faster healing means less additional health risk and loss of activity. Clinical studies confirm the benefits of light therapy, such as reduced pain, reduced bleeding at the incision site, faster healing * and reduced scarring *.
Fibrosis suppression. The following plants can be used as anti-fibrotic agents for long-term use.
• Licorice (Glycyrrhiza glabra) root. It is taken as a water infusion: 1 tsp. root, aged in 1 tbsp. boiling water for 15 minutes three times a day *. During treatment, you should monitor blood pressure, as well as follow a diet high in potassium.
• Milk thistle (Silybum marianum) seeds. Usually used against liver fibrosis, but it can be an effective anti-fibrotic agent for other organs * *. The usual dose of milk thistle seed powder is 1 tbsp. twice a day.
Although not proven, it is highly likely that the combination of these herbal remedies will have a synergistic or at least cumulative effect. Iodine preparations and vitamin D * also counteract the abnormal accumulation of extracellular matrix proteins.
Inhibition of fibrosis using a topical dressing with collagen cream can markedly accelerate the recovery of the lymphatic system and promote the regeneration of normal capillary lymph nodes in an open wound, and ultimately reduce the symptoms of lymphedema.
Reducing preoperative anxiety
Relief of symptoms of lymphedema. Removal of lymph nodes during surgery often causes lymphatic edema, which is called lymphedema. Arm lymphedema develops in 10-35% of patients who have undergone axillary surgery or radiation therapy for breast cancer. Lymphedema that occurs in the first 18 months after surgery or radiation is described as acute lymphedema. It is suggested to treat it with conservative measures such as raising the arm and light compression. If lymphedema does not improve within a specified period, it is described as chronic. This is a more serious form that has a progressive and, as a rule, irreversible development.
Although the arm on the side of the operation is recommended to be used in the usual way, it should not be overstretched with weights or other loads. It is also not recommended to overheat it by taking a hot bath or visiting the sauna. You should also not wear tight-fitting clothing or jewelry on this arm, so as not to impair blood flow. This arm should not be subjected to tests such as injections, blood sampling, or blood pressure measurements.
A decrease in the number of lymph nodes and a violation of their architecture not only impairs lymph flow and contributes to its local accumulation, but also increases the risk of infection. To prevent this, you should protect the hand on the side of the operation from injuries, cuts and burns. For example, with extreme caution, you should do a manicure on this hand.
From herbal remedies in severe cases, you can try the Sweet yellow clover (Melilotus officinalis). Six-month supplementation of sweet clover extract at a dosage of 400 mg/day in patients with postoperative chronic shoulder lymphedema caused in half of them a decrease in the circumference of the affected arm by 5% compared with baseline values *. A combination of sweet clover with bromelain and rutin (100 mg of natural sweet clover containing 20 g of coumarin, plus 300 mg of rutin and 100 mg of bromelain) can enhance this effect *.
A combination of probiotics, prebiotics, and a low-calorie diet for several weeks can also reduce hand lymphedema, as well as improve serum levels of TGF-β, IL-10 and adiponectin * *.
Relief of pain. To reduce postoperative pain, tramadol (2'000 mg/day) can be taken, which, unlike morphine, does not suppress but, on the contrary, enhances immune function *. This concerns the stimulation of NK cell activity *.
Improved postoperative prognosis. Combination of antioxidants (2'850 mg/day vitamin C, 2'500 μg/day vitamin E, 32.5 μg/day beta-carotene, 387 μg/day selenium, other vitamins and minerals), essential fatty acids (1.2 g/day of γ-linolenic acid and 3.5 g/day of ω-3 fatty acids) and coenzyme CoQ10 (90 mg/day) significantly improves survival and quality of life, and significantly reduces the risk of tumor metastasis to the lymph nodes in the armpit in patients with high risk category *.
Infusions of PGG-glucan (commercial beta-glucan) reduced the incidence of infectious complications in postoperative patients by 2.4 times, the duration of the need for intravenous antibiotics by 25 times, and significantly reduced the duration of intensive care *. One dose (0.5 mg/kg) was administered 12-24 hours before surgery, the second dose 1-4 hours before, the third dose 24 hours after surgery, and the fourth dose 96 hours later. Injections of PGG-glucan (2.0 mg/kg) also significantly reduced the number of postoperative infections *.
In an open study, oral intake of brewer's yeast beta-glucan (7.5 mg/day for 15 months) was found to be protective against cancer recurrence after surgery. There were no relapses in the treatment group compared to 22% in the control group with no additional treatment or placebo *.
Removing a large number of cancer cells from the primary tumor facilitates further therapy. The fewer cancer cells left, the higher the chances of success. However, if there is a choice, it is better to resort to less traumatic methods that create a lower risk of metastasis *.
Many complementary cancer treatments can be used during a course of chemotherapy. However, there are many conflicts between orthodox and complementary treatments, between chemotherapy and complementary treatments. If the patient is taking any medications that cannot be discontinued, he should consult with his doctor to find out if they are compatible with the drugs he is about to prescribe.
Compatibility problems arise when one substance neutralizes or interferes with the action of another, or vice versa, enhances its action. Combinations of most chemicals have been studied very poorly. Therefore, the easiest way is to prohibit any additions to the standard protocol, which is usually done by the attending physicians. The responsibility for the desire to improve the treatment process is thus shifted to the patient. In the same time, there are many clinical studies that the patient can rely on.
If the decision is made to use standard chemotherapeutic drugs, we have the opportunity to enhance the effect of chemotherapy, mitigate its side effects, promote tumor suppression, prevent metastasis and promote remission with additional means. However, due to the fact that they may have contraindications, or affect the planned procedures, their use is certainly worth considering together with the attending physician. If he, of course, wants to discuss this topic.
Strengthening the cytotoxic effect of chemotherapy and radiation therapy. Currently, there are experimental methods of treatment that can significantly reduce the doses of cytotoxic agents – insulin-potential therapy (IPT), targeted chemotherapy, glycolysis inhibitors. You can try to find clinics where such treatment protocols are used, or discuss with your doctor the possibility of using them in your particular case.
Strengthening the cytotoxic effect of the main active substance. Given the possible negative interaction between the main therapeutic substance and any other supplement, not all additions to the main treatment may be beneficial. Additives that can cause problems include St. John's wort, echinacea, licorice, and Siberian ginseng. However, there are clinical studies supporting the benefits of some other herbal supplements.
• Docosahexaenoic acid (DHA). Women with metastatic breast cancer who received 1.8 g/day of DHA, excluding the day of chemotherapy (cyclophosphamide/fluorouracil/epirubicin), improved survival rates compared to the median norms *. DHA, which is a dietary component of oily ocean fish, did not cause any additional side effects of the treatment.
Increased oxidative stress. Many natural substances can increase oxidant levels, helping chemotherapy drugs kill cancer cells through oxidative stress. When certain natural antitumor agents are combined with chemotherapy drugs, the cytotoxic effect of the latter is increased. Each of these can lead to the destruction of cancer cells through different but complementary pathways.
The weakening of the cells' energy reduces their ability to resist chemotherapy. Cancer cells, like other rapidly proliferating cells, require an increased expenditure of energy, and therefore suffer from energy hunger much more than normal cells.
Pre-treatment of cancer cells immediately before a chemotherapy session with substances that are selectively toxic to cancer cells (curcumin, quercetin, aspirin, ashwagandha, withania) contributes to disruption of their mitochondria * *. And mitochondrial dysfunction reduces the production of ATP in the cell and increases the levels of oxidants, thereby reducing the survival of cancer cells.
• Metformin (500 mg/day) significantly enhances the effectiveness of most chemotherapeutic agents, including doxorubicin and trastuzumab, due to its diverse effects. Its main effect is to reduce ATP production by limiting glucose levels. Suppression of glycolysis reduces the ability of cancer cells to both generate energy and create building materials for the production of new cells.
Cancer cells have an alternative energy source for glucose (it is glutamine) and can compensate for reduced glucose supply by increasing glutamine stores. Thus, at least for the duration of anticancer therapy, it would be beneficial to reduce animal protein intake and take glutamine blockers.
A number of natural products can enhance the effects of traditional methods of killing cancer cells, including radiation therapy, and at the same time can protect normal cells from the damaging effects of these therapeutic procedures * * * *. Flavonoids, mixed tocopherols/tocotrienols, vitamin C, docosahexaenoic acid (DHA), selenium, magnesium, and baicalein do not interfere with standard chemo drugs but enhance their ability to kill tumors.
• Vitamin C (2 g daily) may enhance the therapeutic efficacy of doxorubicin, cisplatin, and paclitaxel against breast cancer cells.
• Vitamin K synergistically enhances the action of vitamin C, which increases the sensitivity of cancer cells to conventional chemotherapy *. The antitumor effect of this combination is most pronounced at a C:K3 ratio of approximately 100:1. Vitamins C and K are thought to help avoid mitochondrial dysfunction and restore oxidative phosphorylation.
• Curcumin (6 g/day) for seven consecutive days every 3 weeks enhances the effects of docetaxel in patients with advanced and metastatic breast cancer *.
• Quercetin and genistein act synergistically * with many chemotherapy drugs, including cisplatin. Green tea extract, emodin and ginseng also work synergistically. However, their dosage is often quite high.
• Flaxseed oil and fish oil, due to the presence of omega-3 fatty acids, cause DNA damage in cancer cells, but not in normal cells. This makes the tumor more responsive to radiation and chemotherapy without increasing toxicity to normal tissues * *. In addition, both of them enhance the effect of trastuzumab (Herceptin™).
• DIM in combination with trastuzumab leads to a decrease in the viability of breast cancer cells, inducing their apoptosis and a decrease in clonogenicity *.
• Selenium can enhance the efficacy and reduce the side effects of tamoxifen, doxorubicin, paclitaxel, irinotecan and cisplatin and the resulting therapeutic resistance.
• Aloe (Aloe arborescens) as a mixture taken by mouth starting 6 days before treatment, can double the sensitivity of cancer cells to chemotherapy and double the three-year survival rate of metastatic patients *. It is used (3×10 ml) in the form of a mixture of 300 g of aloe leaves, 500 g of honey and 40 ml of 40% alcohol as a preservative.
Weakening of the defense of cancer cells. Chronic inflammation that accompanies a tumor promotes the production of fibrin, and fibrin creates a protective coating for cancer cells, which makes it impossible to recognize antigens on their surface, and also makes it difficult for immune cells to absorb them. Under such conditions, increased immune activity will affect healthy cells of the body, causing autoimmune reactions. Whereas cancer cells will largely remain protected by glycogen mucus and fibrin. The dissolution of fibrin protection can enhance the therapeutic effect of chemotherapy and immunotherapy, as well as significantly reduce the ability of the tumor to metastasize.
• Proteolytic enzymes allow you to get rid of excess fibrin. These can be enzymes of both animal and plant origin. The first include trypsin and chymotrypsin, the second – papain, bromelain, serrapeptase and nattokinase. Proteolytic enzyme supplementation significantly improved patient prognosis and reduced side effects of radiation and chemotherapy *.
Introduction to the cell cycle. The most commonly used chemotherapy drugs, called mitostatics, aim to kill cells that are dividing when they are at their most vulnerable. Due to the fact that not all cancer cells are in mitosis at the time of a chemotherapy session, several treatment sessions have to be performed. However, even this does not guarantee that all cancer cells will be affected by mitostatics, since cancer stem cells can be in a dormant state for a longer time than the entire treatment cycle. For a guaranteed defeat, they need to be brought out of dormancy and introduced into the cell cycle at the time of the action of chemotherapy drugs.
While under normal conditions, stimulating cancer cells to divide is not what we want, during chemotherapy it can enhance the effectiveness of the treatment. However, it is not recommended to independently undertake activities that could stimulate mitosis.
Suppression of drug resistance. Some supplements help prevent the development of tumor resistance against chemotherapeutic agents.
Iodine supplementation (3-6 mg/day), starting from 7-35 days before surgery, and continuing the entire period of doxorubicin therapy, almost completely abolishes the resistance of cancer cells to drugs in patients with stages II-III of the disease. Among iodine-treated patients, compared to non-iodine patients, the rate of complete response doubles *, and the five-year survival rate quadruples *. It's unbelievable how such a cheap supplement can have such a huge impact on the outcome of a treatment.
Pre-treatment with resveratrol or ellagic acid starting 48 hours prior to treatment with cisplatin (10 μM) resulted in a modest (2-3-fold) increase in the sensitivity of cancer cells to primary in vitro cisplatin therapy. With the constant presence of resveratrol or ellagic acid, exposure to cisplatin for 26 weeks completely prevents the development of resistance to cisplatin in vitro *.
Many substances show the ability to counteract already developed drug resistance.
Plant origin polyphenols are able to participate in the restoration of apoptosis mechanisms, such as p53 * *.
The piperine contained in black pepper, as well as some other natural substances, impair the functioning of cellular pumps that eject chemotherapy drugs from the cell.
Other natural substances can destroy heat shock proteins that protect cancer cells. As a result, the drug resistance of cancer cells can be reduced.
Intermittent fasting † or a fasting-mimicking diet enhances the activity of the endocrine therapeutic drugs tamoxifen and fulvestrant, promoting tumor regression and attenuation of acquired drug resistance. In addition, both fasting and a fasting-mimicking diet prevent tamoxifen-induced endometrial hyperplasia *.
Destruction of cancer stem cells. Orthodox methods of treatment are aimed at destroying the array of cancer cells, but they do not affect the cancer stem cells, which causes post-therapy enhancement of tumor resistance and its subsequent recurrence. Therefore, the effectiveness of chemotherapy can be significantly increased if part of the therapeutic effort is directed to the destruction of cancer stem cells.
• Salinomycin, an antibiotic that selectively targets cancer stem cells, can significantly enhance the effect of standard chemotherapy and prevent relapses. However, salinomycin is highly toxic to mammals, which may limit its clinical use.
• Paclitaxel, in combination with parthenolide contained in tansy, inhibits the growth of cancer cells more effectively than either of these substances alone. This phenomenon is called synergy. While paclitaxel destroys the bulk of cancer cells, parthenolide targets cancer stem cells, inhibiting their ability to form colonies.
• Tranilast is 4th generation antihistamine (H1-histamine receptor blocker). Tranilast inhibits the formation of colonies and mammospheres of stem cells of both HER2+- and TNBC-tumors that survived after the use of mitoxantrone *. In experiments on mice with a grafted mammary tumor (4T1), tranilast halved its growth compared to the control, and also reduced the risk of metastasis to the lungs and liver by up to 90% *. Dosage: 500 mg/day *.
• Metformin in combination with doxorubicin also works synergistically to kill both stem and non-stem cancer cells *.
After discontinuation of this combined treatment, the animals remained in tumor remission for at least 60 days, which is consistent with the idea of complete destruction of the tumor. In animals, oral metformin effectively enhanced several standard chemotherapeutic agents (doxorubicin, paclitaxel, carboplatin) * *.
In these studies, the human equivalent intake of metformin was approximately 1'500 mg/day, which is not higher than the maximum dose prescribed for the treatment of type II diabetes.
In mice, the combination of metformin during the day (equiv. 250 mg) and melatonin at night (equiv. 1 mg) significantly inhibited the growth of transplanted HER2 tumors *.
Some natural products are able to directly kill cancer stem cells * *.
Improved drug delivery. Increased intratumoral pressure impairs local blood flow and counteracts the flow of drugs to the therapeutic target. This can significantly reduce the effectiveness of chemotherapy and increase the risk of treatment failure. Of all the means considered to reduce intratumoral pressure, there are very few affordable and cheap ones.
• Dexamethasone is an anti-inflammatory corticosteroid drug, presumably able to reduce intratumoral pressure by reducing the density of the extracellular matrix. In experiments on mice, intraperitoneal administration of dexamethasone caused a drop in pressure inside the tumor up to 45%. The dosage used here is equivalent to about 60 mg/day in humans. The effect began to appear after 4 days of injections, however, it reversibly disappeared within 3 days after its termination *.
• Losartan™, used to lower blood pressure, reduces the production and density of extracellular matrix proteins, collagen and hyaluronan, thereby improving blood flow through the tumor *. The addition of losartan to chemotherapy can double the transport of cytotoxic drugs into the tumor. At the same time, the therapeutic dosage for humans, calculated on animal models, is approximately 120 mg/day. Such a high concentration of losartan can cause a significant decrease in blood pressure, and is therefore undesirable for people who do not suffer from hypertension. Local injections could achieve greater success with fewer side effects, but this approach has not been clinically studied. Another problem of losartan is the need for long-term use (from 1.5 years more). In addition, its combination with selective COX-2 inhibitors such as celecoxib is not recommended.
• Imatinib (Gleevec™) may contain breast carcinoma not only by its anti-fibrotic effect on fibroblasts by inhibiting their proliferation and collagen synthesis, but also by reducing intercellular pressure and suppressing the growth and invasiveness of cancer cells *.
• Serrapeptase improves the penetration of antibiotics into inflammation due to the ability to dilate capillaries and control their permeability. It can be cautiously assumed that other proteolytic enzymes (papain, bromelain) and blood flow agents (aspirin, centella, ginkgo biloba) may also improve blood flow and improve delivery of chemotherapeutic agents to the tumor. However, any of these proposals should be evaluated by a specialist for the absence of contraindications.
Reducing the negative side effects of chemotherapy and radiotherapy helps patients better tolerate effective doses.
Chemotherapy causes cancer-promoting changes that can occur both inside and outside the cancer cells. Chemotherapy drugs increase the expression of anti-apoptotic genes * and increase the ability of cancer cells to migrate and invade * (internal changes). In addition, they incline non-cancerous cells in the host body to not prevent cancer cells from being transported to remote sites* (external changes).
Despite the reduction in the size of primary tumors, chemotherapy alters the tumor microenvironment, which leads to an increase in the release of cancer cells into the bloodstream and their further spread, and the decrease in immune function due to chemotherapy increases the chances of their survival. In addition, chemotherapy makes the tissue microenvironment at distant sites more conducive to receiving cancer cells *.
Therefore, all preventive measures to prevent metastasis recommended during surgery remain valid.
Chemotherapy damages the epithelial layer of the intestine, and therefore there are three problems – bowel cleansing, strengthening the intestinal wall and protecting it – both mechanical and biological.
• Slippery elm and plantago seeds, when combined with water, form a gel-like mucus that has an enveloping effect. In people with a leaky gut, it prevents toxins from seeping through the intestinal wall; and in patients undergoing chemotherapy, it protects the affected intestinal epithelium and promotes healing.
• Bentonite clay is very fine and completely free of sand and other solid impurities. Therefore, when combined with water, it forms a soft mud gel-like mass, which acts envelopingly and, like activated carbon, has high absorbent properties. In addition, bentonite is rich in alkaline minerals and has an antioxidant effect.
During anticancer therapy, it is also worth considering the possibility of a temporary change in the usual diet.
The death of a large number of healthy cells will require a large number of amino acids to create new cells to make up for these losses. This means that you will need to increase your protein intake. Although animal protein is more complete, vegetable protein is preferable in this case. It is poorer in methionine, which causes inflammation and promotes the growth of cancer cells.
Damage to the inner lining of the gut may require you to forgo coarse fiber in favor of more delicate foods, increase your meal frequency, increase pre-shredding, increase your fluid intake, and increase your intake of healthy fats. This will create a food mass that is more gentle on the intestinal walls.
Since linoleic acid is converted to the pro-inflammatory arachidonic acid, it is wise to keep only vegetable fats that are poor in linoleic acid (such as linseed oil, coconut oil, palm oil, cocoa butter, and olive oil) in the diet, and increase consumption of fish oil and saturated animal fats such as lard and butter.
At the same time, you should not only completely abandon simple carbohydrates, but also possibly reduce the amount of complex carbohydrates in order to keep cancer cells on a starvation diet. So that this does not entail constipation caused by a decrease in fiber intake, bran can be added to food, and for those who have gluten sensitivity, psyllium husks, which are washed down with plenty of water.
Chemotherapy affects other epithelial cells. This is most clearly manifested by hair loss, as well as lesions in the oral cavity and in the intestines of the patient.
• Psyllium extract (Plantago major), a solution of 0.12% chlorhexidine and 5% sodium bicarbonate, used as a mouthwash, has been shown to be effective in the treatment of grade II-III oral mucositis in cancer patients in a randomized, triple-blind, phase III clinical trial *.
• Curcumin can be used in place of chlorhexidine mouthwash to rapidly heal treatment-induced oral mucositis in patients *.
• Quercetin (2×250 mg) for 4 weeks may reduce the incidence of oral mucositis in patients undergoing high-dose chemotherapy *.
Chemotherapy affects immune cells and blood cells. Neither surgery, chemotherapy, nor radiation therapy stop the spread of cancer. They do not and cannot destroy all cancer cells in the body. Many cancer cells survive toxic and mitotic stress due to improved fitness and are ready for further reproduction with renewed vigor. Their final elimination falls on the shoulders of the immune system. However, in a person who has undergone orthodox cancer treatment, the immune system is weakened because chemotherapy suppresses immune function, which is so necessary at this critical moment.
In addition to the fact that a decrease in immune function can significantly reduce the effectiveness of treatment, patients remain vulnerable to attack by viral and bacterial infections for a long time. To reduce the risk of infectious diseases, they are advised to strengthen hygiene measures, avoid contact with potential carriers of infections, and use a protective mask during SARS epidemics.
There are several suggestions that help maintain immunity even in the face of chemotherapy.
• Inositol. Patients who received a combination of inositol with inositol hexaphosphate (IP6) during 6 months of chemotherapy did not experience a drop in the number of leukocytes *. The daily dosage of the mixture was 2×3 mg.
• Cimetidine (800 mg/day) significantly improves lymphocyte levels in patients treated with 5-fluorouracil for a variety of cancers *.
• Sage (Salvia Miltiorrhiza) (20 mg/kg extract) in combination with Turkey tail (Trametes versicolor) (50 mg/kg extract) when taken regularly orally significantly improves immunological function in patients by increasing the percentage and absolute number of B-lymphocytes and T-helper cells, as well as the ratio of CD4+ (T-helper cells) to CD8+ (T-suppressor and cytotoxic T-cells) * *.
• Codonopsis (Codonopsis pilosula), Lingzhi (Ganoderma tsugae), Female ginseng (Angelica Sinensis) and Pelargonium strong-smelling (Pelargonium graveolens) have also been shown to be effective in breast cancer patients undergoing chemotherapy. Taking this mixture for 6 weeks halved the radiation/chemotherapy-induced drop in white blood cells and tripled the drop in neutrophils compared to the placebo group *. At the same time, the difference in the levels of T-cells, T-helpers, cytotoxic T-cells and natural killers in patients of both groups was insignificant. The weight ratio of dry aqueous extracts of these Chinese plants was 9:1:22:125, respectively, and the dosage was 4'250 mg/day.
• Astragalus (Astragalus membranaceus) can inhibit tumor development, reduce the toxic effects of chemotherapy, enhance the body's immune function, and improve the quality of life of patients *. A mixture of other Chinese medicine plants (Astragalus membranaceus, Poriae cocos, Atractylodes macrocephala, Lycium chinense, Ligustrum lucidum, Paeonia lactiflora, Paeonia obovata, Citrus reticulata, Ophiulia difficile, Scutellaria barbata, Prunella vulgaris and Glehnia littoralis) at a dosage of 2 g/day in within 21 days significantly decreased anemia and leukopenia in patients treated with chemotherapy, compared with the control group *.
• Cat's claw (Uncaria tomentosa) reduces the side effects of chemotherapy such as decreased neutrophil levels and damage to the DNA of normal cells * *. The level of neutrophils in women with breast cancer (stage II A/B) who took 300 mg/day of an alcoholic dry extract of cat's claw remained at a high level, while in the group who did not take it, the level of neutrophils decreased by more than half *. Two weeks before surgery, cat's claws should be discontinued as this may increase the risk of bleeding.
• White mistletoe (Viscum album), in combination with traditional antitumor therapy has shown a positive result in the vast majority of patients with various types of cancer, including breast cancer patients, without causing serious side effects.
One review presents pooled data on 74 patients with various types and stages of cancer treated with mistletoe as adjunctive therapy to various conventional therapies. Mistletoe extract, brand name Isorel™, was taken every other day between chemotherapy courses. The follow-up period for patients ranged from 4 months to 13 years. The efficiency of the extract was evaluated by such results as prevention of tumor recurrence (in 47% of patients) and cancer regression (in 38% of patients). The best results were achieved with non-metastasizing cancer. During the observation period, there was no obvious deterioration in health status. The antitumor effect of the crude aqueous extract is higher than that of any of its components alone *.
Mistletoe extract in the form of intraperitoneal injections of Helixor® subjectively significantly improved the quality of life and somewhat reduced chemotherapy-induced neutropenia * *. Here the drug was administered 3 times a week in gradually increasing doses from 1 to 50 mg of the raw plant product.
Other commercial analogues of Helixor® – Iskador®, Helixor®, Euriksor® or Lectinol® in most cases show a similar effect *.
Chemotherapy damages the liver. A huge amount of toxins enter the body of a patient undergoing cytotoxic chemotherapy, so it is very important to accompany this process with detoxification measures. Both the waste products and decay of the tumor, as well as the remains of cytotoxins, can enter the bloodstream. In this case, it will be difficult for the liver to quickly neutralize such a large amount of toxins that have entered the bloodstream, which can lead to toxicosis and acute liver failure.
Chemotherapy causes cardiotoxicity and fatigue.
• Ginkgo biloba (Ginkgo biloba) extract is an excellent tool for the prevention and reduction of acute cardiotoxicity caused by doxorubicin and, apparently, it will also be useful in case of therapy with other chemotherapy drugs. The group of patients with stage IV breast cancer who received ginkgo extract (2×120 mg) in addition to doxorubicin therapy had less cardiac lesions compared to the control group *.
• Iodine shows strong cardioprotective properties in rats during doxorubicin treatment *.
• Coenzyme Q10 (2×100 mg). A number of animal studies have shown that CoQ10 prevents doxorubicin-induced cardiotoxicity without compromising its antitumor effects * *. In clinical studies, coenzyme Q10 has shown a good cardioprotective effect with adriamycin * and anthracycline * * therapy.
• Green tea has also been shown to be beneficial in preclinical studies in reducing doxorubicin damage to the heart *.
• Ashwagandha (Withania somnifera). The root extract of the plant (3×2 g), taken orally by patients at stage II and III of the disease throughout the course of chemotherapy, allowed to reduce the average fatigue index caused by the procedures. In addition, their overall 24-month survival rate was 72% versus 56% in the control group *. Lower dosages can normalize thyroid hormone levels *.
• L-carnitine is an endogenous amino acid that transports fatty acids into the mitochondria. Patients who received 3 g L-carnitine before each cycle of chemotherapy and then 1 g/day for the next 21 days had no anthracycline-induced cardiotoxicity, in contrast to the placebo group *.
Chemotherapy causes a weakening of brain activity, manifested in the form of impaired attention, speed of information processing, memory impairment *.
• Omega-3 fatty acids in the form of EPA (200 mg/day) and DHA (1000 mg/day) can halve the incidence of neuropathy *.
At the same time, sugar consumption (sucrose and fructose) causes a decrease in the neuroprotective ability of ω-3, leading to increased neuroinflammation and deterioration in brain function *.
• Ginkgo biloba extract (2x60mg) taken throughout chemotherapy and for 1 month after it helps prevent chemotherapy-induced cognitive decline *.
• Donepezil is a drug used in Alzheimer's disease to improve the transmission of nerve impulses. Women who took donepezil 5 mg/day for up to 24 weeks of chemotherapy had better results in some parameters of memory function compared to women who did not take it *.
Chemotherapy and radiation therapy increase the inflammatory level due to the appearance of a large number of dead cells. And inflammation, in turn, stimulates the growth of surviving cancer cells *. In fact, injecting dead tumor cells into small tumors inoculated into mice accelerates their growth by a factor of a hundred *. Therefore, it is so important to reduce the level of inflammation with the means discussed above.
Chemotherapy disrupts the spectrum of intestinal microflora, which indirectly enhances negative side effects and may reduce the effectiveness of treatment. The condition and bacterial profile of the intestinal microflora can directly and indirectly influence the effectiveness of such anticancer drugs *, as oxaliplatin, cyclophosphamide *, as well as 5-fluorouracil, fluoropyrimidine and others *.
Yoghurts, other dairy and encapsulated probiotics will provide bacteriological protection of the intestine in the face of chemotherapy damage. The presence of growth factor IGF-1 in dairy products in this case should not scare us, because stimulating cell division will introduce them into the division phase – a period when they are especially sensitive to chemotherapy drugs. By inducing cancer cells to divide during chemotherapy, we expose them to the attack of cytotoxic agents.
Mitigation of the negative effects of chemotherapy can be achieved with the help of some other supplements.
• Ginger and chamomile can relieve nausea and vomiting caused by radiation or chemotherapy *. Dry ginger root extract 250mg capsules is taken three times a day for six days, starting three days before the first day of chemotherapy *. Instead of the extract, you can take 1.5-2 g of dry root powder.
• Lycopene (2×25mg) taken orally 24-72 hours after cisplatin administration may help relieve kidney damage in cancer patients *.
• Omega-3 fatty acids (900 mg/day) reduce the incidence of chemotherapy-induced mucosal lesions such as stomatitis and diarrhea *. Omega-3 fatty acid supplementation improved the overall survival of breast cancer patients treated with conventional chemotherapy by approximately 7% *. Conjugated linoleic acid (7.5 g/day) for at least ten days prior to surgery or chemotherapy reduced markers of cancer cell proliferation in women with breast cancer* *.
• Aspirin reduces the risk of thromboembolism caused by cytostatics and tamoxifen, although the use of aspirin for this purpose may not be very significant *.
• Melatonin (20 mg once at night) during seven weeks of radiation and chemotherapy caused fewer side effects of chemotherapy compared to the placebo group *. In combination with various chemotherapy drugs, melatonin helps to significantly reduce their toxicity and increase the 1-year survival rate *. In addition to standard chemotherapy drugs, melatonin is well combined with natural active ingredients, for example, contained in aloe leaves (2 ml/day) *. In addition, melatonin aggravates the sensitivity and reduces the drug resistance of breast cancer cells to the effects of chemotherapy drugs*.
• Modified water. Replacing tap water intake with hydrogen-enriched water for 2 months reduces oxidative stress on healthy tissues, improves inflammatory markers, and increases gut flora diversity *. In addition, such water reduces cisplatin-induced renal dysfunction, at least in rats *. Electroactivated reduced (catholyte) water shows the same protective effects in mice *. In addition, catholyte (alkaline) water, compared with control, delays the development of mammary tumors in animals, reduces their multiplicity and significantly increases tumor-free survival *.
Chemotherapy and radiation therapy increase oxidative stress. Antioxidants such as vitamin C, melatonin and vitamin E have been shown to protect animals from drug toxicity without interfering with the antitumor effect of the drugs. Not only do they protect healthy tissue from free radical damage caused by chemotherapy, but they also act as an immune booster. Women who took antioxidants (vitamin E, vitamin C, multivitamins) immediately after being diagnosed with invasive breast cancer had an 18% lower risk of mortality and a 22% lower risk of recurrence *.
Antioxidants also protect the patient from some of the negative side effects of radiation, including ulcers and fibrosis. These effects are often due to inflammation, and antioxidants can counteract this. Especially useful in this regard are vitamin E, fish oil and silymarin. A combination of different antioxidants is likely to be more effective than a single supplement.
There is strong evidence that a number of natural products have powerful anti-cancer effects on a large number of cancers, even the most resistant forms. However, oncologists continue to urge their patients not to take natural antioxidant foods. Some of them do not even advise eating fresh vegetables, believing that they will interfere with treatment.
Their argument is that radiation and chemotherapy create massive amounts of free radicals that kill cancer cells. Therefore, taking antioxidants during chemotherapy sessions seems counter-intuitive and counterproductive. However, in the hours before and after the treatment, dietary antioxidants appear to be more beneficial than harmful because they usually have a very rapid (0.5-1 hour) absorption period and an equally rapid (3-4 hours) absorption metabolism and excretion period.This circumstance requires an increase in their intake (2-4 times a day).
The effectiveness of antioxidants is highly dependent on their initial stock in the body, as discussed †. With initially low levels of antioxidants, adding antioxidants during chemotherapy can protect normal cells, not cancer cells. And with initially high levels of antioxidants, they can also protect cancer cells. This can partly explain the paradoxical fact that high doses of antioxidants during treatment in some cases reduce the therapeutic efficacy of chemotherapy drugs.
Despite these valid concerns, evidence from clinical studies supports the use of some (but not all) antioxidant supplements in breast cancer patients. For example, vitamin C and E supplements after diagnosis were associated with a 20-27% lower risk of relapse and an 18-22% lower risk of death compared to those who did not take them * * *. However, combined carotenoids were associated with a 23% increased risk of recurrence and a two-fold increased risk of death from cancer *.
This may be due to the fact that some antioxidants exhibit a prooxidant effect when oxidized. Accordingly, carotenoids in a highly oxidizing environment will be oxidized, showing a negative effect instead of a positive one. Fortunately, in combination with other vitamins, they will oxidize much less actively, and their negative oxidative effect will be reduced.
An example of an antioxidant supplement is «Optimal Health 51+» †. Of course, it is not necessary to use this particular complex, but the composition of such complexes * allows you to determine the list of necessary antioxidant components:
- vitamin A (palmitate) – 5000 IU/day,
- vitamin B1 (thiamine mononitrate) – 4 mg/day,
- vitamin B2 (riboflavin) – 5 mg/day,
- vitamin B3 (niacinamide ascorbate) – 30 mg/day,
- vitamin B6 (pyridoxine hydrochloride) – 5 mg/day,
- folic acid – 800 μg/day,
- vitamin B12 (cyanocobalamin) – 10 μg/day,
- vitamin C (calcium ascorbate) – 1500 mg/day,
- vitamin D3 (cholecalciferol) – 400 IU/day,
- vitamin E 400 IU (d-alpha-tocopheryl succinate – 300 IU/day) + (d-alpha-tocopheryl acetate – 100 IU/day),
- biotin – 200 μg/day,
- pantothenic acid (D-calcium pantothenate) – 10 mg/day,
- calcium citrate – 225 mg/day,
- magnesium citrate – 125 mg/day,
- zinc glycinate – 15 mg/day,
- selenium (seleno-L-methionine) – 100 μg/day,
- chromium (as chromium picolinate) – 50 μg/day,
- N-acetylcysteine (NAC) – 250 mg/day,
- coenzyme Q10 – 200 mg/day,
- R-alpha-lipoic acid – 45 mg/day,
- L-carnitine – 100 mg/day,
- natural mixed carotenoids – 15 mg/day.
Supplementation begins at least 48 hours before the start of standard therapy and continues for 1 month after its completion. Clinical trials show that these maintenance doses of micronutrients reduce the risk of tumor recurrence *.
But again, the effect of antioxidants, as mentioned above, depends on their initial level in the breast tissue. Because we don't have a reliable way to measure it, taking antioxidants can cause mixed reactions. In addition, let's not forget that vitamins and other supplements are not a medicine, but a means of replenishing the missing substances when they are inadequately supplied from food.
Oxidative stress increases overall inflammatory levels, and it seems prudent to turn to the anti-inflammatory agents discussed earlier in the «Anti-Inflammatory Therapy» † section. Since fatigue and sleep quality are associated with changes in inflammatory markers in breast cancer patients undergoing chemotherapy *, this is also worth looking into.
Recommendations of integrative medicine. Society for Integrative Oncology * based on clinical research, has provided a set of recommendations for the use of complementary therapies during and after breast cancer treatment * *.
Acetyl-carnitine * is not recommended for neuropathy.
Soft yoga can help with sleep disorders *.
Features of nutrition during anticancer
The diet of cancer patients should be based on foods and drinks that do not feed cancer cells or interfere with treatment.
Protein provides cancer cells with a ready-made building material for creating new cells. Therefore, cancer patients seem to benefit from reducing their protein intake to the physiological minimum of 0.8 grams per 1 kg of body weight *. However, in chemotherapy, when a large amount of amino acids is required to restore dying healthy cells (primarily blood cells and immune cells), some increase in protein intake may be justified. In this case, it would be more reasonable to choose vegetable protein. It contains a sufficient amount of essential amino acids, but few amino acids that promote the growth of cancer cells.
The epithelial cells that line the surface of the large intestine renew themselves very quickly and are easily damaged by the cytotoxic drugs used during chemotherapy. Therefore, during this period, a diet sparing intestinal cells is recommended. Flaxseed *, chia and ginger, due to their ability to create mucus, can reduce mechanical trauma to the epithelium of the gastrointestinal tract with food mass.
Starvation. Short-term fasting (allowing only water) has been shown in limited studies to significantly improve general well-being and reduce chemotherapy-induced symptoms *. Healthy cells are metabolically more flexible than cancer cells, and therefore, when glucose is deficient, it is easier for them to switch to the consumption of fatty acids and ketone bodies. At the same time, tumor cells adapt worse to starvation. Glycolysis cells require a large supply of glucose, proteins and growth factors, the deficiency of which makes them weaker and more susceptible to chemotherapy *. Intermittent fasting protects normal cells from various chemo drugs while weakening cancer cells * * *.
In healthy cells, nutritional deprivation activates protective metabolic pathways that stop cell division, clear the cell's cytosol, and direct energy to increase stress resistance, including multidrug resistance. At the same time, in tumor cells, this protective effect is suppressed due to genetic/epigenetic mutations in metabolic pathways that incline the cell to uncontrolled growth. In addition, calorie restriction can alter the characteristics of the tumor microenvironment, impairing cancer cell supply, decreasing circulation of growth factors, and reducing local inflammation *.
In preclinical models, fasting cycles alone have been shown to be sufficient to slow down tumor growth. In some cases, fasting was as effective as chemotherapy and worked synergistically with standard therapy * *. Experiments on rodents confirmed these observations. If crizotinib or fasting alone reduced the growth of the grafted tumor by about a third, then their combination – by the same amount *. A slight weight loss in animals during fasting was quickly compensated in between fasting cycles. In dogs, 24-hour fasting prior to chemotherapy significantly reduced the incidence of doxorubicin-induced vomiting *.
The size and number of tumors in rodents caused by a chemical carcinogen were significantly reduced by dietary caloric restriction * *. In one of the experiments, it was found that a decrease in calorie content has a more noticeable effect on the appearance of a tumor than on the rate of its further development *. That is, the preventive effect of a low-calorie diet is more pronounced than the therapeutic one.
In addition, 50% caloric restriction in mice had a strong anti-leukemic effect. After exposure to gamma radiation, only 3% of the rodents in the experimental group developed leukemia, while in the experimental group fed ad libitum, leukemia developed in half of the animals *. Other similar experiments on animals showed similar results * *.
A clinical study showed that in patients with HER2-subtype breast cancer, fasting for 36 hours before and 24 hours after chemotherapy reduces the side effects of chemotherapy *. In another clinical trial, patients with stage II-III HER2-negative breast cancer who adhered to a fast that began 24 hours before chemotherapy (docetaxel/doxorubicin/cyclophosphamide) and ended after 24 hours after it had a significant increase in the average number of red blood cells and platelets 7 days after treatment, as well as reduction of chemotherapy-induced DNA damage and/or acceleration of its recovery *. The reduction in the severity of side effects of chemotherapy in this study was not significant, which can be explained by a too short period of fasting: for serious changes in the level of growth factor IGF-1, a longer period of fasting is required * *.
In another clinical study, fasting in patients with various types of cancer continued for 48 hours before platinum-based chemotherapy and 24 hours after it. Increasing the duration of fasting to 48 and 72 hours reduced DNA damage in leukocytes, and slightly reduced neutropenia compared to fasting for 24 hours. IGF-1 levels were reduced by 30%, 33%, and 8%, respectively, at 24, 48, and 72-hour fasts *. The side effects of chemotherapy were most easily tolerated by patients in the 72-hour fasting group.
Another review described 10 cases of cancer patients who voluntarily fasted for a total of 48-140 hours before and/or 5-56 hours after chemotherapy. They experienced significant reductions in chemotherapy-induced symptoms such as vomiting, diarrhea, weakness, headache, nausea, abdominal cramps, dryness, and mouth ulcers *. Side effects were only a feeling of hunger and dizziness. However, there was no reason to believe that short-term fasting interferes with the effectiveness of chemotherapy or protects the tumor. Unfortunately, the number of scientific reports is limited, so this topic requires additional research.
In contrast to short-term fasting, long-term fasting has the potential to increase the survival of cancer cells by increasing their autophagy * *. It can be assumed that long-term fasting may be an effective mechanism for treating a tumor *, if it is combined with immunomodulators and autophagy inhibitors, but this approach has not yet been practically studied.
It is not yet clear how fasting can affect the occurrence of relapse and patient survival. However, short-term fasting in combination with chemotherapy is a promising strategy to increase the effectiveness of chemotherapeutic agents and reduce their negative effects. However, it is safe and well tolerated * *, however, like any other therapy, it has a number of conditions, caveats and control points.
Although there are several fasting therapies *, standard protocols for short-term fasting for cancer have not yet been developed. The attending physician will most likely disagree with this idea. Thus, the decision to fast during chemotherapy remains the responsibility of the patient.
The ketogenic diet may be an additional strategy for the treatment of various types of cancer, including breast cancer.
The classic therapeutic ketogenic diet is defined as a diet with a daily intake of 1 gram of protein per kilogram of body weight, 10-15 grams of carbohydrates, and the remaining calories from fat *. In fact, it is a low-calorie (~ 1'600 kcal/day) diet where 75-90% of all energy comes from fat (preferably medium chain), 8-20% from protein, and 2-6% – from carbohydrates (if possible, complex) *.
The goal of the ketogenic diet is to put the body into a metabolic state called ketosis. In ketosis, cells are forced to feed not on glucose, but almost entirely on ketone bodies (β-hydroxybutyrate, acetoacetate, and acetone), which are metabolized from dietary fat. The therapeutic goal of the ketogenic diet is to create energy starvation for highly glycolytic (cancer) cells by depriving them of an abundant supply of their primary energy source, glucose. It is assumed that as a result of a lack of energy, the bulk of cancer cells will die through apoptosis, and the survivors will significantly slow down their growth.
Glucose can be converted into energy either by oxidative phosphorylation in the mitochondria or by fermentation in the cytosol of the cell. The first metabolic pathway is characteristic of normal cells, and the second is characteristic of cancer cells. Unlike glucose, ketone bodies are not a fermented source for energy production, and are only metabolized in the mitochondria (by oxidative phosphorylation).
Therefore, to effectively switch their metabolism from glucose to ketone bodies, cells must have functional mitochondria. In cancer cells, the mitochondrial mode of energy production is to some extent weakened due to the degradation of mitochondria, and glycolysis, although enhanced, provides very little energy per unit of glucose compared to mitochondria. For this reason, the life of cancer cells is very dependent on the supply of glucose.
Ketone bodies and fatty acids are not fermentable and therefore cannot replace glucose in cells with defective mitochondria. Ketone bodies also suppress glucose uptake in the body. Thus, the ketogenic diet severely limits the ability of the cell to obtain energy from glucose. This means that cancerous and non-cancer cells with dysfunctional mitochondria will lack energy and their risk of death will be increased *. To effectively switch metabolism from glucose to ketone bodies, cells must have functioning mitochondria. In cancer cells, the mitochondrial mode of energy production is to some extent weakened due to the degradation of mitochondria, and glycolysis, although enhanced, provides very little energy per unit of glucose compared to mitochondria. For this reason, the life of cancer cells is very dependent on the supply of glucose.
Ketone bodies and fatty acids are not fermentable and therefore cannot replace glucose in cells with defective mitochondria. Ketone bodies also suppress glucose uptake in the body. Thus, the ketogenic diet severely limits the ability of the cell to obtain energy from glucose. This means that cancerous and non-cancer cells with dysfunctional mitochondria
While glucose can be metabolized at any concentration of oxygen, ketone bodies and lactate can only be metabolized by cancer cells when sufficient oxygen is present *. Therefore, cells in the most hypoxic places, such as tumor tissue, will suffer the most from a ketogenic diet. It will be more difficult for them to produce energy from ketone bodies, even with functional mitochondria.
We can enhance the effectiveness of the ketogenic diet by further reducing the intake of glutamine, another source of energy for cancer cells, obtained as a result of protein metabolism *. At the moment, no highly effective and safe inhibitors of glutaminolysis have been proposed. Affordable, although ineffective means of inhibiting glutaminolysis are green tea polyphenols *. Although ketones by themselves reduce the absorption of glutamine, it seems reasonable to limit protein intake, especially animal protein, which is a very abundant source of glutamine. It is easier to prevent the intake of glutamine than to deal with it later.
In addition, acetyl-L-carnitine may also be useful in this therapy, as it helps transport fatty acids into the mitochondria of healthy cells.
Theoretically, a ketogenic diet can: simultaneously affect several factors of rapid tumor growth; facilitate the delivery of drugs to the tumor tissue; enhance the effect of anti-glutamine strategies; reduce acidity in tumor tissue; increase metabolic efficiency in normal cells *. Thus, she looks like a worthy candidate for complementary therapy. However, an increase in the concentration of ketones in the body has a deeper and more diverse effect, and not always positive.
In one study in mice on an unrestricted diet, a ketogenic diet caused a significant reduction in blood glucose, tumor growth rate, and a 57% increase in mean survival time compared to controls, and its combination with hyperbaric oxygen increased survival time by up to 78% *. Even simply supplementing food with ketones significantly prolonged the survival of mice with metastatic cancer *. Unfortunately, not all studies have shown such convincing results.
In 2020, about 60% of preclinical studies (mostly glioblastomas) reported an antitumor effect of the ketogenic diet, 17% found no effect on tumor growth, another 10% reported adverse or pro-tumor effects, and the remainder were inconclusive *. Additional toxicity and deterioration of the blood count due to the transition to a ketogenic diet was not detected *.
That being said, the ketogenic diet does not seem to be universal, its effectiveness may depend on the type or even subtype of cancer, genetic background or tumor associated syndrome * *. It is most promising for myoglioma (one of the forms of brain cancer); but in breast cancer, anecdotal clinical studies show more modest results. And yet, in clinical studies, ketosis for 3 weeks improved biological markers in HER2 breast cancer *.
A ketogenic diet for 3-12 months can significantly reduce patients' blood glucose, body mass index, total cholesterol, triglycerides, low-density lipoprotein (LDL), and improve high-density lipoprotein (HDL) levels * *. The drop in glucose levels is accompanied by a drop in insulin and insulin-like growth factor (IGF-1) levels *, a decrease in lactic acid levels in tumor tissue *, and insulin-activated enzymes * *.
A controlled clinical study on a 3-month ketogenic diet in breast cancer patients undergoing standard chemotherapy showed a 36% reduction in TNF-α levels in the experimental group, as well as a slight decrease in insulin and IGF-1 levels. With locally advanced cancer, the tumor shrank compared to its original size: in the experimental group of patients by 50%, and in the control group by 15%. However, no reduction in tumor size was observed in metastatic cancer *.
In this study, the daily caloric intake in the experimental group was reduced from 1'704 kcal to 1'325 kcal, and in the control group from 1'767 kcal to 1'600 kcal. The share of fats in the total calorie content in the experimental group was 74%, protein – 19%, carbohydrates – 7%; and in the control, respectively, 30%, 15% and 55%. As you can see, even a regular, but low-calorie diet allowed chemotherapy to reverse the development of the primary tumor.
A woman with TNBC who received chemotherapy, hyperthermia, and hyperbaric oxygen concomitantly with a 6-month ketogenic diet was also reported to have a complete clinical, radiological, and pathological response *, however, this was the only clinical report of remission associated with a ketogenic diet.
There are a lot of resources on the Internet to help those who want to switch to a ketogenic diet *. However, many of the proposed diets are not strictly speaking ketogenic, but are merely high-fat diets that may not achieve ketosis, and therefore will not achieve the goal, and only worsen the initial conditions.
In fact, the ketogenic diet is not a high absolute fat diet, it is a high relative fat diet, this is a low-calorie diet with very low levels of carbohydrates and proteins, which automatically increases the proportion of fat in total calories. The absolute amount of fat consumed, if it increases, is not radical.
Many practitioners of the ketogenic diet overlook another important circumstance – the need to constantly monitor the level of ketosis. Therapeutic ketosis zone is defined as sustained hypoglycemia (glucose levels ~ 2.5-3 mM/L, i.e. 55-75 mg/dL) with elevated blood ketone levels (~ 4 mM/L; at least 2 mM/L , and not more than 10 mM/L) *. You should be guided by the ratio of ketones:glucose in the blood, equal to 1:1, or higher, in mM/L. Sustained ketosis over the next 6-8 weeks allows cancer cells to become more sensitive to chemotherapy for glioblastoma * and radiotherapy for glioma *. A reliable indirect indicator of the state of ketosis is the smell of acetone in the exhaled air *.
Patients are usually told to eat mostly fat, with small amounts of oily fish, cheese, meat, nuts, avocados, and non-starchy vegetables. One of the leading figures on the ketogenic diet, Thomas Seyfried, recommends a smooth transition over several days so that the metabolic switch does not cause stress, which is usually done * *.
Fats recommended for a ketogenic diet are olive oil, coconut oil, butter, avocado oil, macadamia oil, fish oil. All of them do not tend to cause hormonal signaling (MTOR, leptin, insulin) and inflammation. Refined coconut oil containing at least 85% medium chain triglycerides (MCTs) is generally recommended. Although saturated fats are much more readily and more fully converted to ketones than polyunsaturated fats, it may still be reasonable to maintain a ratio of saturated to unsaturated fats of ~1:4 even on a ketogenic diet. And the ratio of fats ω-3:ω-6 ~ 1:3.
If you follow the guidelines for a ketogenic diet, then at 1'800 kcal/day, your macronutrient weight intake would look something like this: carbohydrates 8 g/day, protein 36 g/day, fat 180 g/day. In terms of ordinary food, this can be represented as 20 g of bread, 150 g of meat and 200 g of butter per day. With a further decrease in calories to 1'200 kcal/day, this amount will have to be reduced by a third.
The consumption pattern should be adjusted according to the results of measuring the level of glucose and ketones in the blood. If dietary guidelines are followed but glucose levels are not low enough, reduce carbohydrate and protein intake. If the level of ketones is not high enough, increase the fat component of the diet without going beyond the specified daily calorie content. If you need to reduce the level of glutamine, reduce the protein intake.
The consumption of 200 grams of fat per day is in absolute terms even more than in such record-breaking breast cancer countries as Belgium and France. Numerous observational studies show that when eating without calorie restriction, an increase in the proportion of fat in total calories above 20% is associated with an increased risk of breast cancer. In rodent studies, the incidence of breast cancer increased in parallel with the increase in energy from fat, up to a value of 35%E, after which it reached a plateau *.
With the same calorie content of the diet, an increase in the proportion of fat in the energy coming from food occurs mainly due to a decrease in the proportion of carbohydrates. Thus, an increase in the incidence of breast cancer is associated with a change in the ratio of carbohydrates:fats in total calories. At a ratio of 3.5:1, the risk is minimal, but at a ratio of 1:1, the risk is doubled †. In the ketogenic diet, an even greater deterioration in this proportion is proposed – 1:10. However, the available data indicate that the negative impact of fats, if any, is weak in low-calorie diets *, which may alleviate our fears.
In addition to the advantages of the ketogenic diet, there are also disadvantages. The ketogenic diet is unnatural and uncomfortable, which is why most studies have found poor adherence to it *. Basically, patients increase their daily calorie intake. However, studies in mice have shown that a ketogenic diet without calorie restriction can increase body weight and glucose levels*, which of course would be counterproductive. Therefore, it is worth emphasizing once again that the ketogenic diet is, first of all, a low-calorie diet.
In experiments with mice on a diet without calorie restriction, injections of ketone bodies increased the growth of TNBC tumors by about 2.5 times *. This is not proof, but is in good agreement with the high incidence of cancer in diabetics who have increased ketone production. Ketones, like lactate, strongly influence the expression of genes that enhance the «stem» characteristics of ER+ cancer cells *, which significantly reduces patient survival. In rats, a long-term ketogenic diet without calorie restriction, when compared to an equal-calorie standard diet, causes blood acidification (ketone bodies are acidic), anemia (lower levels of red blood cells, hemoglobin and hematocrit), and a drop in antioxidant enzyme levels *.
Preclinical studies show that a ketogenic diet without calorie restriction cannot lower blood glucose levels and curb tumor growth * * * * * * * * *. While additional calorie restriction and an increase in the proportion of fat due to proteins and carbohydrates leads to a significant decrease in blood glucose levels and inhibition of brain tumor growth * * * *. All of these data lead to the conclusion that the antitumor effect is actually due to the reduction in total caloric intake, which reduces the level of circulating glucose, and diets without calorie restriction are of little effect against cancer.
A high-fat diet can increase the load on the liver, which converts fat into ketones; on the kidneys, which excrete decay products; on the pancreas, which produces fat-splitting enzymes; and on the gallbladder. All this can create some problems in patients with chronic problems of these organs.
The ketogenic diet increases the amount of peroxide lipids, impairs the supply of glucose to erythrocytes, neurons and other cells that are unable to efficiently metabolize fats. The ketogenic diet is contraindicated in type I diabetics, hypertensive patients, patients with a high body mass index and the elderly. Side effects of ketogenic therapy can include nausea, diarrhea, constipation, weakness, fatigue, dizziness, insomnia, and acetone breath odor.
It has also been reported that ketone bodies have more than just antitumor effects. They themselves can behave as oncometabolites, and the enzymes involved in their metabolism are metabolic oncogenes. There is some genetic evidence that the production and reuse of ketone bodies leads to the progression and metastasis of breast tumors *. Ketogenic fibroblasts provide the production of ketone bodies directly in the tumor, and cancer cells use them to produce energy in their mitochondria. The theoretical foundations of the ketogenic diet remain, unfortunately, insufficiently developed.
The classic ketogenic diet is incomplete. Even when consuming nutrient-rich foods, it significantly reduces the intake of many phyto- and micro-nutrients *, which can negatively affect the result of treatment. This is especially true of food polyphenols, vitamins B, C, D, K, as well as iodine, selenium, potassium, calcium, zinc, iron and magnesium. Thus, the ketogenic diet requires appropriate supplementation *.
With insufficient fiber, a ketogenic diet will threaten to upset the balance of the intestinal microflora and increase bacterial penetration through the intestinal wall. Degradation of the gut microflora can destabilize the microflora of other organs, reduce immunity, cause vitamin deficiencies, and increase the risk of colon cancer *. Therefore, on a ketogenic diet, fiber supplements can be recommended, as well as plant-based protein instead of animal protein. Manipulation studies have found that whey or plant protein based ketogenic diets have a safer profile and provide a healthier microbiota composition than animal protein formulations *.
Despite the strong theoretical background, to date, there is not enough conclusive evidence demonstrating the effectiveness of the ketogenic diet against long-term tumor progression or overall survival in cancer patients *, as most clinical studies are observational, uncontrolled, and short-term.
Just like fasting, a short-term therapeutic ketogenic diet could theoretically be absolutely beneficial before any surgery, during radiation * or chemotherapy *. Naturally, in the absence of contraindications and with the approval of the attending physician. However, it cannot be recommended as a regular eating style even when supplemented with micronutrients, fiber, probiotics, and fat-splitting enzymes. Even when the ketogenic diet is used to achieve weight loss, it does not show significant benefits compared to a low-calorie, low-fat diet * * *.
All varieties of the long-term ketogenic diet can cause a sustained rate of bone loss measured in the spine *, presumably due to the fact that ketones are acidic compounds. They can also cause gastrointestinal problems in patients *. In addition, they prevent muscle building *, can contribute to weakening of the heart muscle and, not excluded, even catastrophic weight loss in cancer patients (cachexia).
The persuasive advantage of the ketogenic diet is the reduction in the energy supply of cancer cells, but the same success can be achieved by more humane and gentle, and at the same time less dangerous and uncomfortable methods *. For example, a low-calorie, low-glycemic vegetable diet, which is accompanied by regular fasting, as well as an increase in the duration of night fasting, imitation of fasting, etc. *. Although ketogenic diets did marginally outperform fat-restricted diets in terms of improved health outcomes in short-term studies *, they did not appear to be any better in the long term * while maintaining all of the disadvantages listed above.
Despite widespread hopes for a ketogenic diet, it is still experimental. Single clinical studies show very optimistic results when used for a limited time. As for the long-term ketogenic diet, there is still no convincing clinical evidence that its pros outweigh its cons for most people *. Reducing calorie intake to a physiological minimum eliminates the apparent benefits of a ketogenic diet, which remains deficient without the addition of those nutrients that are naturally present in a high-fiber diet.
Physical activity. Intense exercise during a course of chemotherapy has a positive effect on breast cancer survival. Within a year of treatment, women who did aerobic exercise experienced a significant reduction in fatigue, relief of general symptoms, reduction in overweight, improvement in emotional state, and more likely to return to work *.
Exercise during and after breast cancer treatment clearly reduces overall mortality, regardless of age, body mass index, and disease stage of patients *. And this is perhaps the only medical manipulation that gives us joy.
There are two types of radiation therapy. External beam radiation therapy uses equipment that is located outside the body to send radiation to the tumor. Internal radiation therapy uses radioactive substances in sealed capsules that are placed directly in or near the tumor, inside the body.
Both of these approaches not only attack cancerous cells, but also inevitably damage healthy cells – either nearby or in the path of the gamma rays. If exposure becomes unavoidable, try to find a clinic that can more accurately target the tumor and be more gentle on the body, such as using a gamma knife or proton radiation.
Ionizing radiation destroys protein structures and molecules, including cell organelles and DNA, and creates a high concentration of free radicals, which leads to the death of affected cells. In fact, radiation creates a mild internal burn, similar to that which can be observed on the skin under the influence of radiation. The subsequent severe inflammation can restart the repair processes of tissue that are tangled and chaotic in the tumor.
Many natural substances, as well as some over-the-counter products used for other purposes, can increase the effectiveness of radiation therapy and reduce the severity of its side effects.
Strengthening the effectiveness
Increased oxidative stress in some cases can be achieved using the following means.
• Sulfasalazine, an anti-inflammatory drug, depletes intracellular stores of the antioxidant enzyme glutathione *. This reduces the ability of cells to compensate for the damaging effect of reactive oxygen species and increases the radiation sensitivity of CSCs.
• Mebendazole, an antiparasitic drug, increases the sensitivity of cancer cells, including TNBC cells, to radiation therapy in vitro *. Mebendazole (equiv. 1.7 mg/kg intraperitoneal) aggravates the sensitivity of TNBC cells to ionizing radiation in animals and prevents the development of treatment-resistant breast cancer cell phenotypes *.
• Tylenol, an analgesic and antipyretic drug. Acemitophen within four hours after intraperitoneal injection (equiv. 40 mg/kg) reduced the level of glutathione in mice by 70-80% *.
• Parthenolide from Feverfew (Tanacetum parthenium) causes near-total depletion of glutathione and death of cancerous leukemia stem cells while at the same time causing, with significantly less toxicity, limited and reversible depletion of glutathione in normal cells *. In vitro parthenolide (20 μM) alone significantly suppressed the viability of TNBC cells (MDA-MB231, BT20 and MDA-MB436), while having only a moderate effect on healthy cells *. In mice inoculated with TNBC tumor (MDA-MB231), it significantly reduced tumor growth and increased animal survival *. In prostate tumor-grafted mice, parthenolide (eq. 8 mg/kg) protected normal but non-tumor prostate tissue from high-dose radiation-induced apoptosis *. The low bioavailability of parthenolide remains a problem.
• Vitamin C in the form of a high-dose intravenous infusion (equivalent to 25 g/day) also depletes intracellular antioxidant stores and also inhibits glycolysis by starving glycolysis cells *. Both of these effects could enhance the effectiveness of radiation therapy. Additives of doxycycline additionally reduce the cellular energy obtained from aerobic respiration. A 2-week pre-treatment with doxycycline (200 mg/day) could presumably enhance the effects of vitamin C *.
Depletion of intracellular antioxidants could help achieve the desired effect at a lower level of exposure. But doctors, for a number of reasons, are unlikely to agree to a change in the treatment protocol. Their position is understandable: the process of controlling the level of antioxidants specifically in the tumor presents significant difficulties and does not allow for its objective control.
The question of which of the two options to choose – oxidant or antioxidant, causes irreconcilable controversy.
An oxidative approach, one might fear, can increase the destruction of not only cancerous cells, but also healthy cells, as well as exacerbate some of the side effects of the treatment. However, the remedies listed here show positive effects in studies. It can be assumed that normal cells are able to restore intracellular reserves of antioxidants faster than cancer cells. If this unproven assumption is correct, then administration of glutathione-depleting drugs should be administered over a period of 3-4 hours, and completed 1-2 hours before the start of the radiation therapy session. During this time, they should get into the tumor tissue and accumulate there, but they will have time to largely be removed from the normal tissue.
The antioxidant approach makes it easier for any cells to survive the oxidative stress caused by radiation. However, tumor cells receive less antioxidants due to transport difficulties caused by a dense network of extracellular matrix fibers and intratumoral pressure. Based on these considerations, small amounts of antioxidants can apparently support normal cells without significant support for cancer cells. For the reason stated in the previous paragraph, oral administration of antioxidants is likely to be most beneficial approximately 1 hour before the start of the radiation therapy session. During this time, their concentration should reach a maximum in normal tissue, but will not have time to significantly increase in tumor tissue.
Different antioxidants may have different effects. While glutathione can keep cancer cells alive, dietary antioxidants do not. Dehydroascorbic acid, a metabolic product of ascorbic acid, aggravates the sensitivity of hypoxic tumor cancer cells to radiation therapy *.
Basis on this approach, a complex of vitamins * *, has been developed, which should ensure the best action of antioxidants during radiation therapy, of which there are four main ones: buffered vitamin C (calcium ascorbate, 9'000 mg/day), natural vitamin E (α-tocopheryl succinate, 1'000 IU/day), natural vitamin A (retinol palmitate, 10'000 IU/day) and natural vitamin B (β-carotene, 90 mg/day). High doses of these vitamins increase the effectiveness of radiation therapy, while low doses may conversely promote the survival of cancer cells. Those. in this case, they act not as metabolic, but as therapeutic substances.
During the active treatment phase, these dietary micronutrients are administered orally twice a day, starting 48 hours before irradiation, and continue throughout the entire period of radiation therapy. After completion of treatment, the dosage is gradually reduced by half over a 4-week period, and is maintained during the maintenance phase. Thus, damage in cancer cells begins before radiation, lasts through the therapeutic period, and prevents recurrence after it.
A low level of oxygen in the tumor tissue can increase the radiation resistance of tumor cells, which requires significantly higher doses of radiation to damage them. Therefore, an increase in oxygen concentration could increase the level of free oxygen species and thereby enhance the oxidative effect of radiation therapy.
• Metformin, administered to mice immediately before irradiation, increased the level of oxygen in the tissue, which markedly improved the radiation effect of the treatment of the grafted tumor. And in patients with localized prostate cancer who received radiation therapy, the use of metformin was associated with a significant reduction in early recurrence rates *.
• Melatonin treatment before radiotherapy was associated with a decrease in cell proliferation and an increase in p53 mRNA expression, leading to an increase in the radiosensitivity of breast cancer cells. At the same time, a decrease in side effects caused by radiation was noted in patients with breast cancer *.
• Hyperthermia is an effective adjunct to radiation therapy due to its ability to increase tumor oxygen saturation, and may enhance the action of metformin against cancer cells, including stem cells *.
Impaired DNA recovery. Some substances can enhance the effect of radiation therapy by preventing the repair of protein structures damaged by radiation, which will contribute to the death of irradiated cells.
• Metformin, by reducing the energy supply of cells, can complicate the energy-consuming process of repairing DNA molecules damaged by radiation, and thus increase the sensitivity of cancer cells to radiation therapy. The addition of metformin (2'000-3'000 mg/day) to the standard chemo-radiation protocol using cisplatin has shown an encouraging improvement in 2-year disease-free survival in patients with non-small cell lung cancer *.
• Doxycycline in vitro greatly reduces the expression of the DNA-PK protein, which repairs radiation-damaged DNA, thereby increasing the sensitivity of breast CSC by 4.5 times *. Dosage: 200 mg/day.
• Niclosamide, an anthelmintic drug, significantly enhanced the effects of radiotherapy against triple-negative breast cancer in animals *.
• EGCG (epigallocatechin gallate) capsules (3×400mg) during radiotherapy (2-8 weeks) markedly improved several tumor markers. Compared with patients treated with radiation therapy alone, patients treated with EGCG had significantly lower serum levels of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and reduced activation of metalloproteinase-9 (MMP9) and metalloproteinase-2 (MMP2). Thus, EGCG, the main component of green tea, inhibits the growth and invasion of cancer cells and enhances their death due to γ-radiation *.
• Smoking. Although smoking generates large amounts of free radicals and may enhance the effects of radiation therapy, evidence suggests otherwise. The combined effect of smoking and radiation therapy reduces the effectiveness of treatment. Smokers may be 2.4 times more likely to relapse and 3.4 times more likely to die from all causes * than non-smokers. Therefore, it is highly recommended to stop smoking, at least for the time required for all radiotherapy treatments.
Reduced side effects of radiation therapy.
Antioxidants protect cells from damage caused by free radicals. This reduces the severity of the side effects of radiation therapy, especially when irradiating large areas of healthy tissue or the entire body. However, the danger remains that antioxidants can help cancer cells survive radiation-induced oxidative stress. This dual behavior of antioxidants is the reason for the conflicting research results on their benefit in radiotherapy and the disapproval of their use by medical practitioners.
• Hydrogen-enriched water has been shown in mice to protect against radiation-induced immune dysfunction *, heart disease * and lung disease * without compromising the therapeutic effect of radiation therapy. Patients who received hydrogen-enriched water during radiotherapy for 6 weeks had reduced blood levels of hydroxide oxidizers and significantly improved quality of life compared to patients who received placebo *.
• Alpha-lipoic acid, vitamins C and E can also be used as effective natural antioxidants. There are a great many different substances and coenzymes that directly or indirectly support the body's antioxidant system. These are iodine, omega-3 fatty acids, coenzyme Q10, vitamin K2, bioflavonoids, carotenoids, etc. Many plant foods, especially berries, are a rich source of antioxidants *. However, it is worth recalling once again that we are talking about taking supplements in physiological concentrations, and not about overdoses.
• Selenium increases antioxidant enzymes in normal cells, but not in cancer cells *.
• Ginkgo biloba is taken by mouth within one month after radiation therapy. The leaf extract of the plant acts as an antioxidant, and also helps cleanse the blood and improves blood circulation. The recommended dose of the extract is 100 mg/day.
• Pentoxifylline (3×400 mg/day) and vitamin E (3×100 IU/day) taken orally for six months to a year, starting one month after exposure, may prevent and reverse radiation-induced breast fibrosis * * *
including in high-risk patients *.
In a study of patients with head and neck squamous cell carcinoma, pentoxifylline was administered directly during radiation therapy, resulting in milder subsequent skin changes and less fibrosis than in the control group *.
• Ointment with zinc and copper superoxide dismutase (in a total dose of 40 mg at a concentration of 3600 IU/mg, for 90 days) reduces radiation-induced fibrosis *.
• Oral metformin can significantly reduce skin thickening caused by ionizing radiation and collagen buildup *.
Immune cell support.
• Diclofenac or indomethacin also helps to reverse radiation therapy-induced lymphocyte dysfunction in breast cancer patients, which may increase survival rates *.
• Cordyceps (equiv. 5 mg/kg) in mice protects the bone marrow and intestines from total γ-rays exposure, and accelerates the recovery of white blood cells *.
• Beta-glucan from Reishi mushrooms (equiv. 33 mg/kg) increases spleen weight and white blood cell count in irradiated mice after total exposure to γ-rays *.
Mitigation of radiation dermatitis.
• Melatonin (topically) may help prevent skin irritation from radiation therapy. In phase II clinical trials, a melatonin emulsion (Praevoskin®) was applied to the breasts of breast cancer patients during radiation therapy and for two weeks after it ended. Whereas in the control group 90% of patients experienced radiation-induced dermatitis and skin irritation, in the test group this number was 59% *.
• Curcumin (orally, 6 g/day) reduces the severity of radiation dermatitis in patients with breast cancer *.
• Celecoxib (400 mg/day), although not able to reduce dermatitis, significantly reduces itching and pain caused by ionizing radiation in patients *.
• Acute skin reactions to radiation therapy can be alleviated by topical application of aloe vera juice * * *, green tea * and hyaluronic acid cream * *, but their success may be weak. Aloe extract by itself only slightly reduces the intensity of inflammation caused by radiation therapy * *.
A week after the last procedure, even if you feel normal, you should take at least a general and biochemical blood test, as well as a general urine test. And if you feel worse, this will probably have to be done even earlier so that the doctor can assess the situation and take appropriate measures .
The most common side effects of chemotherapy are nausea, diarrhea, and mucositis. Some dietary changes can help make nausea easier to bear. Nutritionists advise avoiding fatty, spicy, hot, and strong-smelling foods, as well as enriching the diet with protein and moderate fluid intake. To protect the intestinal epithelium, you should refuse food that can injure the intestinal wall, use a blender for cooking, and also increase the consumption of mucus-forming foods, such as liquid oatmeal, camelina, chia or flax.
Chemotherapy usually causes leukopenia. But when analyzing blood, in addition to the number of leukocytes, it is important to understand the absolute number of neutrophils (granulocytes), which significantly protect against infections, especially bacterial ones. When the number of neutrophils falls below 1'000/μl, the risk of infections caused by bacteria found in everyday food increases dramatically. This can lead to the development of fulminant fatal infections. But even with satisfactory indicators of neutrophils, the possibility of bacterial infection should be minimized.
Experts advise strengthening sanitary measures, especially with regard to animal protein and perishable products *. In addition, you can try to boost your immune system by supplementing with probiotics (Lactobacillus bulgaricus, Streptococus thermophillus), vegetable fiber (spinach, cilantro, pumpkin, flax), beta-glucan (mushroom powder, bran, brewer's yeast), fish oil, garlic powder, and other natural remedies. In severe cases, a doctor may prescribe immunostimulants that stimulate the growth of neutrophils, such as Neupogen. This will keep the neutrophil level within 1'500-10'000/μl.
Other supplements that may be helpful include coenzymes CoQ10 (200 mg/day); selenium (200 μg/day); germanium sesquioxide (up to 200 mg/day); vitamin B6 (3×50 mg); vitamin B12 (200-1'000 μg); proteolytic enzymes such as bromelain and papain (1'000 mg/day), aloe juice or extract (2×1-2 ml).
During the break between treatments, it will also be useful to keep records of what complications were observed, the duration and severity of them, what measures were taken to mitigate them, and what was the result. This will help to better control the trends in the course of the disease.
At the end of the first stage of treatment (21-30 days), you should undergo a second examination. Based on the results of the analyzes, it is possible to draw a conclusion about the effectiveness of the course and further strategy.
The subjective criterion for the effectiveness of treatment is well-being. Subjective and objective criteria for assessing the success of treatment:
• Reducing pain.
• Improved well-being.
• Increased appetite.
• Increased energy and endurance.
• Weight gain.
• Increased muscle strength.
• Improvement of blood and urine parameters.
• Reducing the size of the tumor.
• Decreased markers of inflammation.
• Decreased values of oncomarkers.
As a result of treatment, the array of cancer cells of the tumor should decrease, respectively, decrease in size on the image. The more malignant the tumor, the more resizing it must undergo.
The main treatment for cancer, contrary to popular belief, is not so much in the destruction of cancer cells as in the elimination of the causes that led to their appearance and development.
Conventional therapy aims to kill rapidly dividing tumor cells or to suppress specific signals that stimulate tumor growth (eg, EGFR or HER2). After a course of such therapy, doctors, having achieved the disappearance of a visible symptom, consider the work successfully completed. Although, in fact, it is not completed.
Do not assume that from now on, cancer is forever over. The absence of symptoms and good examination results do not mean complete and final victory. The factors that caused the disease did not disappear, which means that a temporary victory was won over the tumor.
Despite the destruction of the tumor array as a result of treatment, there are conditions for its revenge. These are fibrosis and subclones of cancer stem cells that have taken refuge in places difficult for immune cells and therapeutic toxins to survive due to their unique mutations that can withstand the treatment. In addition, extracellular matrix proteins in preserved areas of increased tissue density can contribute to the loss of cell differentiation.
Preservation of seeds (cancer cells) and favorable soil (inflammation, fibrosis, estrogen or oxidative load) create conditions for the return of the disease to the territory cleared of weak cells. Therefore, the usually observed significant initial success is often followed by the emergence of therapy-resistant tumors and the return of the disease.
Reducing the risk of relapse.
Reduced tissue density – incl. proteolytic enzymes. Discussed above, in «Normalization of breast tissue» †.
Reduced inflammatory levels – Antioxidants and anti-inflammatory agents, ω-3 fatty acids, DMSO, oxygenators, antioxidant enzymes, coenzyme CoQ10, metformin.
Weakening of pro-tumor and strengthening of anti-tumor epigenomic influences – broccoli, tea, pomegranate, etc.
Reduced hormonal stress – hormones, aromatase inhibitors, balance of estrogen metabolites.
Lifestyle. Women with longer periods of physical activity (≥ 2.5 hours per week) had a lower risk of total and recurrent/specific mortality compared to women without physical activity *.
Women with triple-negative breast cancer who regularly consume green tea have a 46% lower risk of recurrence and a 43% higher five-year survival after diagnosis than women who do not consume tea *.
Consumption of Black cohosh (Actaea racemosa) may reduce the risk of relapse in patients taking tamoxifen *.
Combining broccoli sprouts and green tea increases tamoxifen sensitivity in ER-negative breast cancer *.
Elimination of micrometastases. Since the process of metastasis begins at the earliest stages of the disease *, a cancer survivor's body can be filled with micrometastatic nodules that can remain dormant for years. You can try different approaches to destroy possible metastatic colonies of cancer cells that have remained hidden after anticancer therapy.
Antithrombotic agents. Cancer cells can migrate and take root in a new hard-to-reach place under the cover of a layer of mucus (glycoprotein) and fibrin *. Pancreatic enzymes (trypsin, chymotrypsin and amylase), as well as proteolytic enzymes of plant origin (papain and bromelain) are able to dissolve the protein coat that masks cancer cells. This exposes mutated antigens on the surface of cancer cells, allowing immune cells to recognize and destroy them.
In addition, metastases are more likely to occur at the site of a clot, where migrating cancer cells can more easily hide in a fibrin clot. Not surprisingly, patients with cardiovascular disease taking antithrombotic drugs have seen a reduction in cancer mortality in general and metastatic cancer mortality in particular *.
However, heparin, aspirin, and vitamin K antagonists are very powerful drugs. They can be used against thrombosis only for a short time, at the discretion of the attending physician and only in the absence of contraindications. But in our case, they are a bad idea, because we need long-term persistent and low-level application.
• Wax moth larvae (Galleria mellonella). Lipase, produced by immature wax moth larvae, is the only relatively available enzyme that can efficiently degrade dense fats such as wax. A therapeutic perspective is the ability of this enzyme to erode the lipoproteins that coat the surface of tuberculosis bacillus and protect them from antibiotics and immune cells *. Wax moth larvae extract greatly reduces blood clotting, and also shows a number of other beneficial effects in experiments on rats * and guinea pigs*.
The human equivalent dosage of the 20% hydroalcoholic wax moth larvae extract used in these studies is approximately 3×15 ml (3×1 tbsp). Although the extract is not toxic even at high concentrations, this dosage is at least three times higher than recommended by therapists. It is taken in courses of 3 weeks each, then 6 weeks off. Note, however, that fatty foods neutralize the action of the enzyme because the lipase is forced to be wasted on dietary fat rather than the therapeutic target. In addition, you should carefully monitor the state of blood pressure, which can significantly decrease.
There are also various antithrombotic substances of plant origin *.
The best solution seems to be a combination of three classes of antithrombotic agents:
- anticoagulants, which interfere with the blood clotting system and prevent the further growth of a blood clot. This, for example, withaferin from the root of Ashwagandha (Withania somnifera) *; wogonin from the root of Baikal skullcap (Scutellaria baicalensis) *; glycyrrhizin from the root of Licorice (Glycyrrhiza glabra) *.
- antiplatelet agents, which reduce platelet aggregation and inhibit the formation of a blood clot. These are, for example, andrographolide from the leaves of Creat (Andrographis paniculata) *; bupleurumin from the root of Sickle hare's ear (Bupleurum falcatum) *; tanshinone IIA from Sage root (Salvia Miltiorrhiza) *; ginkgolide C from the leaves of Ginkgo biloba (Ginkgo biloba) *; diosgenin from Wild yam root (Dioscorea zingiberensis) * *; asiatic acid from the leaves of Pennywort (Centella asiatica) *, ajoene from the bulb of Garlic (Allium sativum) *.
- fibrinolytic agents, which directly dissolve an already existing thrombus. These are, for example, proteolytic enzymes serrapeptase (serratiopeptidase) * (2 tab. 3 times a day); nattokinase * * and lumbrokinase *; as well as paeoniflorin from the root of Chinese peony (Paeonia lactiflora) *.
When using antithrombotic agents, one should not forget about the dosage, as well as possible contraindications and side effects. In particular, they should not be taken before surgery and in case of an abscess. The combination of several antithrombotic agents will most likely act synergistically, and large doses can lead to dangerous internal bleeding. The systematic use of low doses will be more useful, however, in this case, care must be taken.
Anti-inflammatory and anti-fibrotic agents. Chronic inflammation and the resulting fibrosis are not only the cause of primary tumors. Fibrous formations, both in the breast and in other parts of the body, provide a convenient springboard for the occurrence of secondary tumors. In this regard, the importance of anti-inflammatory and antifibrotic therapy does not decrease even after the end of the course of antitumor therapy, when the main array of cancer cells is destroyed.
The most effective enzymes produced by the body that dissolve non-functional healthy cells and benign tumors are pepsin, trypsin and chymotrypsin. Thus, care must be taken to ensure that they are present in sufficient quantities in the blood. To do this, it is necessary to stimulate the work of the stomach, liver and pancreas, for example, taking appropriate herbal preparations and sufficient doses of vitamin B3 (niacin, nicotinic acid). Supplementation with exogenous enzymes such as papain and bromelain, as well as pancreatic enzymes, will also be very helpful. Reduced protein intake combined with intermittent fasting will allow all these enzymes to be used for their intended purpose, and not for the breakdown of dietary protein.
The digestive organs should not be overloaded with heavy or rich food in order to release their enzymes to work against the tumor. In the absence of contraindications, you can also additionally take the proteolytic enzymes serrapeptase, cerrase, nattokinase and pancreatic enzymes (both separately and as part of complexes or dietary supplements).
Long-term, moderate supplementation of nattokinase and serrapeptase can help dissolve nonfunctional masses, scars, cysts, sclerotic plaques, and excess extracellular matrix buildup. In 85.7% of patients complaining of breast engorgement, after 3 days of taking serrapeptase tablets (3×10 mg), edema, induration and pain in the breast decreased *.
The combination of Boswellia extract (200 mg/day) with betaine (700 mg/day), myo-inositol (800 mg/day) and a multivitamin complex suppresses inflammation, relieves pain and reduces increased breast density. After 6 months of taking this mixture, the volume of benign breast tumors decreased * *.
Molecular iodine (6 mg/day) taken over a period of several months subjectively and objectively improves the condition of the breast in fibrocystic conditions * and reduces cyclic breast pain in women *.
Digoxin and other digitalis-based cardiac glycosides taken by patients for heart disease have been reported to significantly improve their prognosis. The mortality rate in chronically treated breast cancer patients was 6% versus 34% in non-treated patients *, and their recurrence rate was 9.6 times lower *. The dosage of cardiac glycosides should be selected individually by a specialist; usually with long-term maintenance therapy, digoxin is taken at 0.125-0.75 mg/day. In this case, most likely, potassium and magnesium supplements will be required, since digoxin contributes to the loss of these elements.
Although the use of digoxin does not increase the risk of recurrence in treated women with breast cancer *, there are studies showing an increased risk of primary breast cancer due to the use of digoxin * * *.
Recovery of immune function. After antitumor therapy, the immune system may not work adequately, facing not only infections, but also new cancer cells that appear in the body. Restoring full immune function may take about six months after treatment, during which time patients remain vulnerable to infections *.
This is especially true of B cells involved in the creation of antibodies, CD4+ cells (helper T cells) and natural killer cells. The level of B-cells, for example, due to chemotherapy may drop to 6% of the initial. And even a year after treatment, the stock of immune cells may not return to pre-treatment levels *. In women who smoked, B-cell recovery was less complete, reaching only 51% of the initial level at 9 months after therapy versus 80% in non-smoking women.
This state of affairs forces one to resort to various methods of restoring immune function, discussed above.
Increased survival and improved quality
Diet. Women on a low-fat diet (≤ 20% of total calories) have a 22% higher survival rate than women on a regular high-fat diet (≥ 30%) *. Reducing fat intake below 20% of dietary energy while increasing intake of fruits, vegetables, and grains can double patient survival after a course of treatment *.
Eating just one serving of cruciferous vegetables a day cuts the risk of breast cancer recurrence in half in women taking tamoxifen *.
High intake of enterolingans (flaxseed, sesame, sunflower seeds, and pumpkin seeds) can also have a significant impact on the survival of postmenopausal breast cancer patients *.
Additives. A meta-analysis of cohort studies found that the use of antioxidant supplements after breast cancer treatment increased patient survival *.
Daily intake for 3-5 years after anticancer therapy of antioxidants (vitamin C: 2'850 mg; vitamin E: 2'500 IU; beta-carotene: 32.5 IU; selenium: 387 μg; other vitamins and minerals), essential fatty acids (gamma-linolenic acid: 1.2 g; ω-3 fatty acids: 3.5 g) and coenzyme Q10 (90 mg) significantly increased the survival of patients in the high-risk group *. Those who took CoQ10 at a dosage of 400 mg/day had the best results *. Taking aloe juice or extract (2×1-2 ml) in combination with melatonin (20 mg at bedtime) has also been shown to significantly improve cancer patient 1-year survival rates *.
Long-term melatonin (≥ 3 mg/day) may reduce bone loss in the elderly *.
Massage. Experiments in mice showed that mild mechanical stretching of the tumor every day (10 minutes once a day for four weeks) halved the growth of transplanted breast tumors without the use of any other therapy *.
Delicacy. When the lymph nodes are removed, the normal flow of lymph is disrupted, which can lead to swelling of the arm on the side of the operation, which is called lymphedema. A disturbed lymph flow makes the hand more vulnerable to infections, which will require special attention.
Compared to women who continue to smoke after being diagnosed with breast cancer, women who quit smoking have a higher overall survival * * *.
Reducing alcohol consumption to at least 10 g of pure alcohol per day reduces the risk of recurrence of primary breast cancer *.
Hormonal contraceptives increase the risk of breast cancer due to hormonal imbalances. And although barrier contraceptives may also increase the risk of breast cancer during a woman's reproductive life by reducing the beneficial effects of male sperm factors *, this risk is an order of magnitude lower than hormonal intervention.
Psychological mood. The stresses associated with diagnosis, treatment, and lifestyle changes can have a very painful effect on the mental state of patients. All of them are worried about the uncertainty about the future, the danger of an early relapse, the possibility of ruining their life plans.
However, in reality, their fears and concerns are often too high. Fear is worse than any most terrible disease. Unlike optimism, fear does not improve, but worsens the situation. Don't let him ruin your life. Breast cancer is not a death sentence. Most cases are treated quite successfully, and are especially effective when the patient is responsible and sympathetic to his diagnosis. With him you need to live on, trying to live to a ripe old age. Live happily and hope for the best, no matter what.
Sometimes the cancer comes back after treatment. This is called a recurrence. Relapse can occur weeks, months, or even years after cancer treatment is completed. There are different types of relapses, depending on where the cancer returned to the body.
Local recurrence is when the cancer returns to the lymph nodes and tissues in the area where the cancer started.
Distant recurrence is when the cancer has spread to another part of the body and formed a new tumor there. The new tumor is called metastasis, or metastatic cancer. With breast cancer, sometimes what happens is the so-called «bilateral cancer» – this is when a new tumor forms in the breast on the other side of the body.
Doctors for these cases have therapeutic protocols of the second and third echelon of defense. And the patient remains to continue the main and additional treatment.
Even when doctors recognize the hopelessness of treatment, we still have the opportunity to prolong the life of the patient and improve its quality. When a cure is unlikely, the focus shifts to the physical, emotional, and practical aspects.
Palliative care. Hydrazine sulfate, D-ribose and MSM (methylsulfonylmethane) are often used to combat cachexia. Hydrazine sulfate breaks the biochemical cycle of cachexia. MSM along with vitamin C can also help the body get rid of lactic acid. D-ribose is able to penetrate lactic acid and support non-cancerous cells from which glucose is taken away by malignant cells.
Adventurous measures. Since with terminal cancer we are no longer talking about remission, but only about increasing the survival period, some patients are ready to risk the most radical actions that are not approved, and even condemned by official medicine. Despite the fact that such actions in themselves threaten to shorten the rest of life. For example, such as high alkaline therapy using cesium chloride. Other equally risky measures include intratumoral injections of calcium bicarbonate, salinomycin, disulfiram.
It is impossible to condemn the patient in such actions when medicine does not give him hope for salvation. It is difficult to dissuade him from dangerous experiments when he is predicted to live for several months without offering any effective solutions. When he is left with a simple choice: die from his crazy idea, or die from the impotence of medicine. In the end, the master of his life is man himself, and he has the right not only to life, but also the right to die. Including self-medication.