Aug
12
2017

Curcumin And Cancer

Many clinicians give their attention to curcumin and cancer. Physicians may use curcumin not as a primary treatment, but may add it as an adjunct to other cancer treatments. Curcumin is the effective ingredient of the old Indian spice, turmeric. The question is how effective curcumin is against cancer? Is it safe to use? What is the evidence?

Frequency of cancer

According to the American Cancer Society there will be 1,688,780 new cancer cases in 2017 and 600,920 cancer deaths will occur in the US.

Causes of cancer

There are many different causes for cancer. Hidden in the many causes may be the possible solution to new cures.

Lack of exercise

A lack of exercise may contribute to the development of cancer because of a lack of tissue circulation. And exercise will help to support your normal cell metabolism (explained below). Wrong foods may or may not have a contributory role regarding cancer development (a high sugar and starch diet causing insulin response, which changes the metabolism). The Mediterranean diet is an anti-inflammatory diet and has been credited to prevent a lot of cancers.

Carcinogens

Chemicals, called carcinogens can cause cancer. But oncoviruses can also cause it. Genetic mutations can also cause cancer. That’s why it tends to run more often in certain cancer prone families. But Warburg has researched the metabolism of cancer almost 100 years ago, even got the Nobel price for it in 1931 and yet the elusive cancer cure has not materialized yet.

DNA mutations, tumor suppressor genes metabolic difference between cancer cells and normal cells

Following Warburg’s research Watson/Crick detected DNA in our cells. Ever since geneticists found this fascinating by it. They also found that a cancer suppressive gene, regulated by the p53 gene could develop mutations and then cancer would occur: tumor suppressor genes. For decades this was the “in” thing. But in the last 5 to 10 years there is a revitalization of the original Warburg idea that one should concentrate on the metabolic differences between cancer cells and normal cells. This is starting to show some timid results. Cancer cells are more acidic from lactic acid and burn glucose for energy without requiring oxygen (anaerobic pathway), while normal cells burn glucose in the aerobic pathway in the mitochondria. This difference is important. Certain manipulations are more likely to kill cancer cells.

Cryoablation therapy for prostate cancer

Take cryoablation therapy for prostate cancer. Cryosurgery for prostate cancer. A local deep freeze method like cryoablation therapy kills the more vulnerable cancer cells preferentially leaving  the normal cells intact. Another example is photodynamic therapy for cancer that has been used for lung cancer and esophageal cancer.  This method may be a lot more universally applicable than believed so far. The physician injects a photosensitized dye, which is normal cells eliminate, but cancer cells retain.  Next the physician uses a laser beam that kills the cancer cells preferentially by absorbing the specific laser wavelength that is specific for the dye.

Consumer driven cancer therapies

Nobody knows which way cancer research is going. But I think that consumers will drive this: consumers want better cures. When new methods have better cure rates, consumers will demand treatments with these. Less effective methods will become history. I think that researchers will revitalize Warburg’s ideas and develop new therapies from this as I indicated.

Curcumin and cancer: malignant conversion

There are three development stages for any cancer to develop.

Originally cancer researchers used skin cancers a model. Later they could confirm that initiation, promotion and progression also were present with the development of cervical cancer. The name for this is “malignant conversion”. This needs to happen before a normal cell transforms into a cancer cell. Here are the three stages.

  • Initiation
  • Promotion
  • Progression

This is important to know in the context of curcumin. Basic research has shown that curcumin interferes with all of these stages of tumor development, both in terms of prevention as well as in terms of being curative. Here is a link that points out the complex multiple steps of cancer growth that curcumin interferes with.

Multiple actions of curcumin

As can be seen from it, curcumin interferes with the initiation of multiple cancers, reduces inflammation, and interferes with angiogenesis and this reduces the amount of metastases that can form. But curcumin further interferes with proliferation of cancer cells, reduces invasion, prevents resistance and improves survival. The underlying molecular and genetic reasons for curcumin’s actions are all contained in that link.

Curcumin and cancer: research in tissue culture and animal experiments

When it comes to cancer research, you usually hear about in vitro culture experiments and animal experiments. This type of research is used to establish that there is an anti-cancer effect, that it is reproducible and non-toxic. The September issue of the 2016 Life Extension Magazine reviewed this in detail. It was entitled “How Curcumin Targets Cancer”.

But as a former clinician I am more interested in seeing cancer patients cured. This has to be verified by clinical trials first. When I looked through PubMed.com for objective evidence of the effects of curcumin in cancer patients, this type of information was more difficult to find. But in the following there are a number of examples that I did find.

Curcumin and cancer: clinical trials

1. Reduction of tumor necrosis factor-alpha

A 2016 meta-analysis of eight randomized studies investigated the effect of curcumin in patients with various inflammatory diseases including cancer. They found that curcumin consistently reduced tumor necrosis factor-alpha. In cancer patients this inflammatory substance is responsible for further cancer growth and developments of metastases.

2. Poor bioavailability of curcumin

A study with increasing amounts of curcumin showed poor absorption of curcumin into the blood. In this study researchers were giving dosages between 500 mg up to 12,000 mg per day of curcumin. 500 mg to 8000 mg of curcumin did not result in any positive serum level of curcumin. Only the higher dosages, 10,000 and 12,000 mg of curcumin, caused positive curcumin levels in the blood.  Patients have to take higher amounts of curcumin to have a clinical response. Toxicity studies were done when using higher amounts of curcumin. The results showed taht it was safe and patients tolerated high dose curcumin fairly well.

3. Precancerous colonic polyps reduced in number and size

A smaller study consisted of 5 subjects with familial adenomatous polyposis (FAP). This is an autosomal-dominant disorder where hundreds of colorectal adenomas develop in the lining of the colon. From these colorectal cancer can arise. Five patients received 480 mg of curcumin and 20 mg quercetin orally three times per day. After 6 months the number of polyps and the size had reduced by 60.4%.

4. Premalignant colonic lesions suppressed by curcumin

44 eligible smoker subjects received a baseline colonoscopy where aberrant crypt foci (ACF) were determined. ACI are the very first focal areas in the colon that lead to colon cancer. Smokers have more of these lesions, which was the reason that researchers chose smoker subjects for this trial. The patients received either a supplement of 2000 mg of curcumin or 4000 mg of curcumin for 30 days. These are fairly high doses. They were used to overcome the poor absorption of curcumin. Colonoscopies were done again after one month of curcumin supplementation. 41 subjects completed the study. In the 4000 mg curcumin group the ACF numbers were reduced significantly by 40% compared to the 2000 mg group, which showed no reduction. The 4000 mg group showed a 5-fold increase of curcumin blood levels compared to baseline. The 2000 mg group had no change in blood levels.

5. Reduction of radiation dermatitis with radiation therapy in breast cancer patients

30 breast cancer patients were divided into an experimental group and a placebo group. All of them had a mastectomy first and subsequently radiation therapy. The experimental group received 6 grams (2 grams three times per day) of curcumin during the time of radiotherapy following mastectomy. The experimental group had  significantly reduced radiation dermatitis following radiotherapy when compared to the placebo group. Only 28.6% had significant radiation dermatitis in the curcumin group versus 87.5% in the placebo group.

6. Chronic multiple myeloma patients

An Australian study involving chronic multiple myeloma patients found that curcumin at 4 Grams per day and even more so at 8 Grams per day stabilized the disease and improved kidney function.

7. Descriptive studies

Descriptive studies investigating the effect of various doses of curcumin have been done regarding breast cancer,  and advanced pancreatic cancer. But these clinical trials were all rather small.

8. Chemoprevention of cancer

A phase II trial enrolled 21 patients with end-stage pancreatic cancer patients. The only FDA approved treatments for this are gemcitabine and erlotinib, but this would normally only lead to clinical responses in less than10% of patients. In this study the investigators used curcumin to enhance the anti-tumor response of either gemcitabine or erlotinib. The study summary stated: “Oral curcumin is well tolerated and, despite its limited absorption, has biological activity in some patients with pancreatic cancer.” 2 of the 21 patients had stable disease for more than 18 months; one of the 21 patients had a brief tumor regression of 78%, but then relapsed and died.

9. Chemoprevention of prostate cancer

Chemoprevention of prostate cancer is discussed in this publication: There was specific reference made to prevention of prostate cancer and the opinion of the researchers was: “At present, there is no convincing clinical proof or evidence that the cited phytochemicals might be used in an attempt to cure cancer of the prostate.”

Curcumin And Cancer

Curcumin And Cancer

Conclusion

For years there have been reports to indicate that curcumin was a promising natural supplement that can improve cancer survival. Many clinical trials regarding the effects of curcumin on colorectal cancer, pancreas cancer, prostate cancer, breast cancer, ovarian cancer and others had a poor design. But on closer look the hype seems to come mostly from in vitro studies (tissue culture experiments) or from animal studies. Clinicians, however, demand well-constructed randomized clinical trials with clear research objectives before they can accept a new agent like curcumin to be effective. These clinical trials are missing! Instead there are many in-between trials of questionable quality as listed above.

Problems with bioavailability of curcumin

There have been problems of bioavailability due to poor absorption of curcumin. Pushing the dosage to 6000 to 8000 mg per day succeeded in overcoming this limitation to a certain extent. But a significant percentage of people (around 30%) suffered from abdominal cramps and nausea and had to discontinue these high doses of curcumin. Researchers have developed newer curcumin compounds, but at this point it is unknown what the bioequivalent dosage is of these newer curcumin agents in comparison to the original curcumin dosages.

It is quite possible that researchers will one day design clinical trials  that will bring better news on survival rates of various cancer patients involving curcumin therapy. But in my opinion right now it is not yet prime time for curcumin!

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Nov
16
2013

You Can Fight Back Against Arthritis

This article is about the fact that you can fight back against arthritis. It is important to realize that osteoarthritis affects about 4 to 5% of the population with women outnumbering men by 2 to 1. Notably, the age of onset typically is less than 50 years, but becomes more evident and more disabling beyond the age of 50. About 40 to 60% of osteoarthritis is genetically linked as twin studies in women have shown (Ref.1). Synonyms for osteoarthritis are degenerative joint disease, osteoarthrosis and arthrosis. Till recently arthritis was accepted as something that was inevitable: people were getting old, getting stiff and sore, and had to “take it easy” as a result when they got older. In general, things are not as uncomplicated, as arthritis affects about 53 million Americans, and it has become the leading cause of disability in the US.

First thing to remember is that rheumatoid arthritis is an autoimmune disease. It is not a disease of “old age” but can affect people of every age group. The body reacts to components in joint tissue, and this immune reaction to collagen will produce inflammation, pain and ultimately disability.

Another key point, so far osteoarthritis was believed to be the result of wear and tear affecting the aging population, but more recently it has been discovered that osteoarthritis is also accompanied by the similar inflammatory immune factors that are involved in rheumatoid arthritis.

Cytokines from the immune system attack joints

In particular, when the body attacks collagen, which is needed to keep the joints moving smoothly, microscopic particles of it wander into the blood stream. There they are perceived as foreign molecules, and the immune system produces inflammatory substances (cytokines). These are sending out an army of “killer T-cells” to combat the collagen, which is perceived as a foreign matter. They are bombarding the exposed cartilage with toxic substances. Certainly, this means a chaotic combination of oxidative stress and more inflammation. Over time the cartilage that was meant to protect the joint in its function to move freely is eroded and destroyed.

Pain in the joints

For the person suffering from this disordered reaction, it means that the joint is not only creaking but causing pain, which is made even worse by weight bearing (walking, standing). Indeed, any person suffering from osteoarthritis will complain that he or she feels stiff and sore especially after a period of inactivity.

Certainly, commercials for anti-inflammatory medication are plentiful, and many sufferers resort to the pain relief that is promised. The warnings are mentioned right after the commercial or on the medication package, if the patient reads the fine print. Most anti-inflammatory medications are causing irritation of the stomach, and the kidneys get damaged (nephropathy)with prolonged use from these pills despite the promises in commercials of a happy, active and pain free life.

You Can Fight Back Against Arthritis

Causes of arthritis

There are many varied causes that can all contribute to developing arthritis. By all means, it is important to take a critical look at lifestyle choices. For instance, excessive body weight puts an additional burden on the joints in the body. Indeed, increased body fat is not just sitting at the abdomen as an inert potbelly. To emphasize, abdominal fat is a highly active metabolic organ that releases inflammatory substances into the blood stream, which distributes them throughout the body. It is known to damage blood vessels.

Inflammation and smoking lead to arthritis

To clarify, inflammation will damage the joints as well. The statistics show that 33.8 % of obese women have arthritis. The percentage for obese men shows that 25.2 % suffer from arthritis. Another key point is that smoking leads to circulatory problems and lack of oxygenation in the body’s tissues. It is a mistake to believe that damage is done only to the lungs or the heart. The joints will be affected as well.

Mechanical stress causing arthritis

Mechanical stress with inadequate self-repair is one cause; misalignment of bones such as knock-knee (genu valgum) and bowleggedness (genu varum) will lead to premature osteoarthritis of the knees as can loss of muscle strength. Exercise without injury does not contribute the risk for developing osteoarthritis; it is actually part of the rehabilitation plan.

According to Ref. 2 there are other causative factors, such as increased age, female sex, race (black women have a twofold increase of arthritis over Caucasian women), estrogen deficiency, nutritional factors, genetics, metabolic and endocrine disorders, joint trauma, joint deformity, occupational factors and sports participation (accumulation of mini injuries).

One of the newer findings is that osteoarthritis is actually an inflammatory condition where numerous destructive processes occur within the affected joints leading to a breakdown of cartilage and supportive synovial fluid factors (proteoglycans). These findings lead to the possibility of new therapeutic approaches discussed below.

Diagnosis of osteoarthritis

According to Ref. 1 there are no blood tests and analysis of synovial fluid is non-diagnostic. Diagnosis of osteoarthritis is made by history, X-rays of the affected joints and clinical findings. There are joint tenderness and swelling of the affected joints. Heberden’s nodes (swelling of the distal interphalangeal joints or DIP joints) and Bouchard’s nodes (swelling of the proximal interphalangeal joints or PIP joints) are present. There can be a decreased range of motion and a grating sound of two ends of bones rubbing together (called “crepitus”).  X-rays show typical osteoarthritis details with a narrowing of the joint space of the affected joint, subchondral sclerosis (increased bone formation around the joint) and new bone formation at the joint margins, called “osteophytes”).

Integrative therapy of arthritis

Ref. 2 points out that integrative treatment of arthritis is aimed at reducing joint pain, increasing joint function and reducing further joint deterioration. Some measures are symptomatic only, others are disease modifying.

Nutrition

Dietary habits can promote good health or have disastrous consequences. The news has been out for some time that the typical North American diet with a high load of omega-6 fatty acids will stoke the fires of inflammation in the body and lead to arthritis, heart disease and cancer. Soybean oil, cottonseed oil and safflower oil contain the cheaper omega-6 oils that are widely used in food processing and bakery products. Refined carbohydrates contribute to unhealthy spikes in blood sugar levels and wreak havoc in their own way paving the downward slope to insulin resistance, metabolic derailment, and diabetes. Take a hard look at your shopping wagon. Stay away from processed foods, shop the periphery of the supermarket, and choose organic meats, vegetables and fruit. Use heart healthy fat in the form of virgin olive oil. A

Mediterranean diet particularly useful

Mediterranean type diet will be a good choice. Just bear in mind, that a heap of pasta like Fettuccine Alfredo does not constitute what a healthy Mediterranean diet is all about. An anti-inflammatory diet such as a Mediterranean diet also includes deep-water fish as a source of omega-3 fatty acids or molecularly distilled omega-3 capsules (you need 7 to 8 high potency, molecularly distilled fish oil, 1000mg per capsule) every day.

This approach has shown beneficial effects in beginning stages of osteoarthritis.

It is important to cut out sugar and starchy foods to reduce insulin resistance, which would otherwise maintain the inflammatory chronic condition causing arthritis and cardiovascular disease. Physicians could show that cutting out wheat and wheat products is beneficial in reducing inflammation. Such an anti-arthritis diet prevents heart attacks and strokes at the same time.

Weight loss

Ref. 2 points out that one study showed that weight reduction of only 10% had a 28% improvement in joint function. Weight reduction in combination with an exercise program makes the improvements even more striking.

Exercise

Exercise consists of aerobic training, resistance training and muscle strengthening. When researchers observed patients with osteoarthritis throughout controlled exercise programs, flexibility and range of motion of the affected joints were improving. They found that a minimum of three days per week of exercise was necessary to show joint range of motion improvements. However, the best results were there when patients exercised most of the days. Joints become less swollen, show improved circulation and less pain. Researchers determined that prior to an exercise program those with increased cardiovascular risk should first undergo an exercise stress test. This measured their cardiovascular reserve and established that it was safe to start a program.

Treat inflamed joint first, then exercise

Physicians found that an acutely inflamed or swollen joint required treatment first before the start of an exercise program. Lack of exercise will promote more disability. While a person with arthritis may be unable to run a brisk race due to joint discomfort, he or she will find water exercises and swimming much more manageable. Group programs for people with arthritis are available and you may enjoy the supportive company.

Heat and cold therapy

Ref. 2 points out that three weekly 30 minute sessions of microwave diathermy for 4 weeks showed a significant reduction of joint swelling in knee osteoarthritis with improved joint function and reduced pain. On the other hand cold packs for aching muscles after strenuous exercises can decrease muscle spasm and increase the pain threshold. Range of motion increased with cold application and there was a reduction of joint swelling. Patients who have cold sensitivity (such as Raynaud disease) need to refrain from the latter treatment modality.

Acupuncture and electro acupuncture

Researchers found these treatments useful as an adjunct to anti-inflammatory medication with NSAIDS (non steroidal anti-inflammatory drugs). The advantage was that they could reduce the dosage of NSAIDS, which eliminated the potential serious side effects of gastric bleeds and kidney damage. Note that people with pacemakers or CNS stimulators cannot use electro acupuncture.

Intraarticular steroid injections

When osteoarthritis or rheumatoid arthritis affects only a few joints, a physician can inject a corticosteroid into the joint. However, there are limitations, as the physician can inject each joint not more than 3 to 4 times. Otherwise there can be damage to the joint cartilage, which would make the arthritis worse. However, I have seen surprisingly good results for a long period of time, which allowed the patients to exercise and stabilize the joints that way.

Complementary treatments

A number of supplements and herbs are effective in reducing inflammation. Omega-3 fatty acids are the precursors for anti-inflammatory prostaglandins in the body, which helps both patients with osteoarthritis and rheumatoid arthritis. As I indicated earlier, only higher doses of omega-3 fatty acids cause this effect. Also, for safety reasons only use molecularly distilled omega-3 fatty acid supplements. These avoid toxicity from mercury and PBC’s. Yes, they are more expensive.

Curcumin

Health care workers in India and Asia used curcumin, the active ingredient of the spice turmeric, for its anti-inflammatory and antioxidant properties for centuries. It helps not only arthritis, but also against the illnesses in association with it, such as obesity, diabetes, heart disease and autoimmune conditions. Ref. 2 points out that curcumin neutralizes inflammatory agents circulating in the blood of patients with arthritis.

Standardized ginger extract

Research showed that standardized ginger extract reduced pain significantly in patients with knee osteoarthritis.

Other common supplements for building up cartilage in the joint are glucosamine sulfate and chondroitin, both available at the health food store. They stimulate glycosaminoglycan formation, which in turn builds up hyaline cartilage, the enamel-like coating of the bone within the joint.

An oral desensitization to treat arthritis

Researchers asked themselves whether itv is possible to enhance joint health of patients in other ways? New answers have emerged. In the past, people who were suffering with colds or flus were consuming a steaming bowl of chicken soup. Colds and flus also cause an inflammatory reaction within the body.

A steaming bowl of chicken soup

While a lot of health professionals dismissed this home remedy as old-fashioned and useless, a team of scientist from the University of Nebraska decided to research the matter a bit closer. They discovered that it was not the vegetables, but a component in the chicken broth that showed anti-inflammatory activity. The chicken derived type II collagen functions to regulate the immune system, so it stops attacking proteins normally found in healthy joint cartilage. Results of a pilot study have shown remarkable results. A dose of 40 mg per day of un-denatured type II collagen (UC-II) showed a significant reduction in pain and swelling from arthritis. It also yielded good results in terms of relief from joint pain and stiffness due to exercise.

Un-denatured type II collagen (UC-II)

Animal studies on dogs and horses demonstrated that both animal groups that frequently suffer from arthritis got significant relief. Human clinical trials with UC-II showed similar effectiveness.

Researchers treated a group of patients with knee osteoarthritis with the supplement for 90 days. 33% experienced a reduction in their osteoarthritis. There was a reduction of knee pain by 40%. Those patients who received the standard treatment without any supplement had 15.4% less pain. There was an improvement of joint function by 20% in the group on the supplement. There was only 6% of improvement in the patient group receiving standard care.

Healthy patients showing more knee mobility on UC-II

Researchers also assessed healthy patients who did not suffer from arthritis, but received the supplement to evaluate how they would fare with exercise-induced knee pain. They treated them with a daily dose of 40 mg of UC-II. After day 90 and 120 the treatment group group with the supplement could exercise for significantly longer periods before experiencing joint pain. They also recovered faster after joint pain. The placebo group who swallowed “fake pills” did not show these changes. When researchers examined knee joint flexibility, the supplement group had significant increases in their knee mobility, but no such luck for the placebo group!

UC-II desensitizes the immune system

Numerous toxicological essays have evaluated the supplement. There is no oral toxicity. Researchers did not detect any mutations in bacterial genomes. This is a standard screen to ensure that a substance is non-carcinogenic.

The oral administration of the UC-II supplement works through desensitization of the immune system. It reverses T-cell attacks on exposed cartilage. If our joints are healthy and intact, we normally do not react to our own cartilage. But the protective barrier between blood and cartilage diminishes as we age. Early treatment with UC-II may help induce immune tolerance even in healthy individuals and protect them from reactions of the immune system to their own cartilage.

Conclusion

The supplementation with UC-II offers a different approach to modify joint inflammation of arthritis. Standard treatment at this point consists mainly of symptomatic treatment. Side effects to the drugs can be serious, if they are in use on a long-term basis. Few are tolerable to modify the course of the disease.

The UC-II supplement addresses the root of the disease (autoimmune disease). The patient experiences relief of symptoms within a few weeks of starting it. A person with arthritis can fight back  with lifestyle changes and the UC-II supplement.

More information on osteoarthritis: https://nethealthbook.com/osteoarthritis/

References

1. “Osteoarthritis. Basic information”. Ferri: Ferri’s Clinical Advisor 2014, 1st ed., © 2013 Mosby

2.  Rakel: Integrative Medicine, 3rd ed., 2012 Saunders