Aug
12
2017

Curcumin And Cancer

Many clinicians give their attention to curcumin and cancer. It may not be used as a primary treatment, but may be added 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 diagnosed in 2017 and 600,920 cancer deaths will occur in the US.

Causes of cancer

Cancer can be caused in many different ways. Hidden in the many causes may be the possible solution to new cures.

  1. 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.
  2. Cancer can be caused by chemicals, called carcinogens. But it can also be caused by oncoviruses. It can be genetically caused, 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. Otto Heinrich Warburg
  3. Following Warburg’s research Watson/Crick detected DNA in our cells. Ever since geneticists were fascinated 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.
  4. 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. Cancer cells were found to be more vulnerable to be killed by certain manipulations.
  5. Take cryoablation therapy for prostate cancer. Cryosurgery for prostate cancer. The more vulnerable cancer cells are preferentially killed over the normal cells through a local deep freeze method. Another example is phototherapy treatment of cancer that has been used for lung cancer and esophageal cancer. https://www.sciencedaily.com/rel… This method may be a lot more universally applicable than believed so far. A photosensitized dye is injected and later when normal cells have eliminated the dye, but the defective cancer cells are still containing the dye a laser beam is used to kills the cancer cells preferentially, absorbing the specific laser wavelength that is specific for the dye.
  6. Nobody knows which way cancer research is going. But I think it will be consumer driven: consumers want better cures, and when new methods appear that have better cure rates, these will be pushed forward while less effective methods will become history. I think that Warburg will be revitalized and new therapies will continue to be developed from this as I indicated.

Curcumin and cancer: malignant conversion

There are three development stages for any cancer to develop.

This was originally researched with skin cancer, but also confirmed with cervical cancer. It is called the “malignant conversion” that needs to take place before a normal cell has become a cancer cell. There are 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.

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 dosages between 500 mg up to 12,000 mg per day of curcumin were given. 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 were associated with positive curcumin levels in the blood serum. In order to have effects of curcumin, higher amounts have to be taken. Higher amounts of curcumin have been tested for toxicity and were found to be safe and were fairly well tolerated.

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 from which colon cancer develops. Smokers are known to have more of these lesions, which was the reason that smoker subjects were used 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, but 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. There was no change in blood levels in the 2000 mg group.

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, which was followed by radiation therapy. The experimental group received 6 grams (2 grams three times per day) of curcumin during the time of radiotherapy following mastectomy. The severity of radiation dermatitis following radiotherapy was significantly reduced in the experimental group 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 cancer

Chemoprevention of 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. There are poorly founded reports of effects of curcumin on colorectal cancer, pancreas cancer, prostate cancer, breast cancer, ovarian cancer and others. 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.

There have been problems of bioavailability due to poor absorption of curcumin. To a certain extent this could be overcome by pushing the dosage to 6000 to 8000 mg per day. But a significant percentage of people (around 30%) suffered from abdominal cramps and nausea and had to discontinue these high doses of curcumin. Newer curcumin compounds have been developed, but at this point it is not known what the bioequivalent dosage is of these newer curcumin agents in comparison to the original curcumin dosages.

It is quite possible that new trials will one day be performed that may 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!

Jul
29
2017

Some Drink Milk, Others Are Lactose Intolerant

Some drink milk, others are lactose intolerant; this is the fact about drinking milk.

For a long time the dairy marketing board advertised with the slogan: “Got milk?”. But dairy milk consumption has declined over the past decades.

Why this is has been reviewed in this article. I like to review the problem of lactose intolerance, milk as a source of calcium to prevent osteoporosis and offer alternatives to milk consumption.

Lactose intolerance

Milk cows have been around in Europe for about 6000 years. But not everybody can tolerate milk products. Most of the Europeans, North Americans and Australians have adjusted the digestive enzymes in their duodenum to produce enzymes, called lactase that digest milk sugar (lactose) into glucose and galactose. But up to 75% of the world population (Africa, South America, Asia) is lactase deficient; they cannot tolerate dairy products. They get abdominal cramping, intestinal gas, bloating, diarrhea, nausea and vomiting from drinking a glass of dairy milk. This link explains why goat milk is better than cow’s milk for those who cannot tolerate cow’s milk.

It is also interesting that many people who are lactase deficient can tolerate cheeses, yogurt and other fermented milk products as the fermenting bacteria have digested the lactose.

Other problems with dairy products

Problems with mass production of dairy items are the following:

  • Concentrated Animal Feeding Operations (CAFO) are responsible for the majority of milk products on grocery market shelves. This means that the animals are fed unnatural corn, which leads to deficiencies and omega-6 fatty acids in the milk products.
  • Antibiotics are given to prevent infections among the herds of animals.
  • Bovine growth hormone (bST, bovine somatotropin) is administered to stimulate more milk production. The antibiotics lead to superbugs in humans, the bST may be causing autoimmune diseases and breast cancer in humans. The healthiest milk is milk from grass-fed cows. It is high in omega-3 fatty acids. All of the milk products derived from this type of milk are also healthy.

Milk as a source of calcium

One key advertising slogan of the dairy industry used to be that milk would be such a good source of calcium, which would prevent osteoporosis. But milk also has a lot of animal protein in it, which acidifies blood. This means that the kidneys use calcium to neutralize acidic blood and excrete calcium. The net result is that there is more calcium leaving the body as some of the calcium from the bone is also used to keep the balance between acidity and alkalinity.

This 12 year long Harvard Nurses’ Health Study involving 77, 761 women between the ages of 34 to 59 showed that a higher consumption of milk did not protect against hip and wrist fractures.

The myth that full fat milk causes heart attacks and strokes

There is another myth floating around, namely that full fat milk would be bad for the heart because of increased saturated fatty acids. But an Australian study showed that full fat milk is healthier for you than milk with less fat.

After 14.4 years of follow-up the group that consumed the most milk compared to the lowest fat intake group had a 69% lower death rate from cardiovascular disease!

A 2016 study showed that consumption of plain yogurt was associated with better health outcomes on the long term. Be more concerned about the sugar content than the fat content of yogurt!

Prevention of osteoporosis

Too many years have been wasted to sell the false concept of increasing milk consumption (“Got milk?”) for increased calcium intake and possible osteoporosis prevention. It was sold like a mantra: Milk-calcium-osteoporosis prevention. Now we know the real truth behind the false advertising mantra: milk provides protein and calcium, but calcium is poorly absorbed and the acidified blood is alkalinized through calcium from milk and from the bone being excreted into the urine. The end result is a net loss of calcium from the bone, as it is more important to the body to keep the blood’s acid/base stable than to increase the calcium level in the bone. Sadly all the high consumers of milk from the Harvard Nurses’ Health Study ended up having fractures from osteoporotic bones.

Prevention of osteoporosis requires intake of vitamin D3, vitamin K2 and calcium (supplement or diet) as I have reviewed in this blog. In addition regular exercise is also very beneficial as is bioidentical sex-hormone replacement. It is interesting that a large clinical trial that I mentioned in this blog showed after 7 years that there were 35% to 38% less fractures of the hip than in the placebo group. Vitamin K2 is essential to keep calcium in the bones and to keep calcium out of the blood vessel walls. Vitamin D3 is important for calcium absorption through the gut wall and to deposit calcium into bone. Without all of these ingredients it is not possible to prevent osteoporosis.

Alternatives to milk consumption

  1. One obvious step is to replace cow’s milk by goat milk. As you can see from this link, there are many advantages to goat milk. What I find important is the fact that those with lactase deficiency often can tolerate goat milk while they would otherwise react to cow’s milk. There are also many goat milk products like cheese and yogurt, all of which are very healthy. They do not contain any antibiotics or bovine growth hormone (bST), which is only used in cows. Goat milk products are also an excellent source of protein.
  2. You can eat a more vegetable-based diet. A lot of vegetables and fruit have calcium and protein in them.
  3. You can consume almond milk instead of cow’s milk. The downside to know is the fact that almond milk is not a significant source of protein. It has the advantage of being slightly alkaline; this will ensure that the calcium absorbed in the gut will reach the bones as long as you also supplement with vitamin D3 and vitamin K2. The many “fake milk” products such as rice milk, coconut milk and hemp milk are also poor protein sources. The only product higher in protein is soymilk. But soy has its own problems: over 90 % of the crop in North America is genetically engineered, and soy is a known allergen. As of recent, another product based on pea protein is available, and the protein content is excellent, so it is worth looking for it (It is called “Ripple”).
Some Drink Milk, Others Are Lactose Intolerant

Some Drink Milk, Others Are Lactose Intolerant

Conclusion

Drinking milk as a source of protein and calcium has become an obsession a few decades back. In the meantime it turned out that drinking milk tips the acid-base balance in the direction of acidity. This causes osteoporosis, as the kidneys excrete all of the calcium from milk that is absorbed. On top of that even more calcium is taken out from bones to recalibrate the acid-base balance.

Up to 75% of the world population is lactose intolerant. They get sick from drinking cow’s milk. But they usually tolerate goat milk quite well. Considering the fact that antibiotics are used in cow milk production and recombinant bovine growth hormone as well, I have joined the crowd that prefers goat milk instead of cow’s milk. I take the supplements I mentioned for bone maintenance (vitamin D3 and K2) and I get lots of calcium also from vegetables and salads. I have no lactose intolerance, but that’s my take on milk.

Jul
22
2017

Relaxation Reduces Inflammation

Relaxation can calm your mind, but new research has shown that relaxation reduces inflammation as well.

This article is based on a research paper in Frontiers in Immunology in June of 2017.

It concentrated on the calming effect of meditation on the nuclear factor kappa B (NF-κB), which causes inflammation. We know that overstimulation of the sympathetic nervous system activates the inflammatory pathway by expressing the genes responsible for NF-κB. These authors showed that the reverse is true also, namely that inflammation can be suppressed through meditation.

This metaanalysis of 18 research papers included 846 participants.

Here are brief summary findings of these 18 studies. Note that diverse relaxation methods had very similar results on the genes expressing inflammatory markers.

1. Qigong practitioners

A group of Qigong practitioners had 132 downregulated genes and 118 upregulated genes when compared to non-meditating controls. Meditation strengthens the immune system and delays cell death.

2. Sudarshan Kriya yoga

One form of yoga breathing is called Sudarshan Kriya yoga. When this form of breathing yoga was practiced for 1 hour per day the stress-related response on white blood cells was shielded compared to controls that did not meditate this way. Those practicing yoga had a strengthened immune system. Genes inhibiting cell death were also strengthened.

3. Chronic lymphocytic leukemia

Eight patients with chronic lymphocytic leukemia were practicing the “seven yoga breathing patterns”; the popular Indian yoga teacher, Swami Ramdev, developed these. Those patients who practiced the breathing yoga technique had 4,428 genes that were activated compared to controls. They showed an up to twofold upregulation, which strengthened their immune system.

4. Loneliness in older people

Loneliness in older people causes inflammation, morbidity and mortality. 55-85 year old volunteers were taking a course of mindfulness-based stress reduction. The researchers wanted to find out whether it was due to increased inflammation that older people were more susceptible to disease. Blood mononuclear cells were tested for genome-wide transcriptional profiling. Those older persons who had reported loneliness had more transcription factors for nuclear factor kappa B (NF-κB) than controls without feelings of loneliness. After an 8-week course those who no longer felt loneliness had a reversal of proinflammatory gene expression. The genes that had changed expression were located on monocytes and B-lymphocytes; these are cells of the immune system.

5. Care workers for patients with mental health problems

Care workers who looked after patients with mental health problems or chronic physical problems have been known to have stress-induced chronic inflammation markers in their blood. A study involving 23 caregivers used a practice of Kirtan Kriya Meditation (KKM) assisted by an audio recording every day for 8 weeks. There were questionnaires filled in for depression and mental health before and after the 8-week trial. Blood samples for transcriptional profiling were also taken before and after the KKM trial. The KKM meditation group had significantly less depressive symptoms and showed improvements in mental health. 49 genes were downregulated and 19 were upregulated compared to the controls. The pro-inflammatory NF-κB expression was decreased; the anti-viral gene expression was increased. This was measured using the IRF-1 gene. This gene controls the expression of the interferon-regulatory factor 1 (IRF-1 gene), which controls the immune response to viral infections. The interesting observation here was that a time of only 8 weeks of meditation was able to reduce inflammatory substances in the blood and could activate the immune system to fight viruses better. Further tests showed that it was the B cells and the dendritic cells that had been stimulated by the meditation.

6. Younger breast cancer patients

Younger breast cancer patients taking a mindfulness meditation course: Another study involved younger stable breast cancer patients after treatment that also had insomnia. Both breast cancer and insomnia were known to be associated with a lot of inflammatory markers in the blood. A total of 80 patients were enrolled in the study, 40 were treated with Tai-Chi exercises, the other group of 40 with cognitive-behavioral therapy. Tai-Chi exercises reduced IL-6 marginally and TNF (tumor necrosis factor) significantly. There was a 9% reduction with regard to the expression of 19 genes that were pro-inflammatory; there was also a 3.4% increase with regard to 34 genes involved in regulating the antiviral and anti-tumor activity in the Tai-Chi group when compared to the cognitive-behavioral therapy group. While cognitive therapy has its benefits, the winner was the Tai-Chi group where 68 genes were downregulated and 19 genes were upregulated. As in the prior study the pro-inflammatory NF-κB expression was decreased, which reduced the inflammatory response.

7.  Study with fatigued breast cancer patients

Another breast cancer study, this time with fatigued breast cancer patients, was observed. The patients practiced 3 months of Iyengar yoga. After 3 months of yoga there were 282 genes that were upregulated and 153 genes that were downregulated. The expression of NF-κB was significantly lowered. This suggests a lowering of inflammation. At the same time questionnaires showed that the fatigue factors had been significantly reduced 3 months after initiating yoga exercises.

8. Mindful meditation used in younger breast cancer patients

A group of 39 breast cancer patients diagnosed before the age of 50 received six weekly 2-hour sessions of mindful awareness practices (MAP). This program is tailored to cancer survivors. In addition to the group sessions the patients also did daily exercises of between 5 minutes and 20 minutes by themselves. The control group consisted of patients on a wait list. The investigators used several psychological measure (depression and stress) and physical measures (fatigue, hot flashes and pain) to assess their progress. Gene expression in the genome and inflammatory proteins were measured at baseline and after the intervention. Mindful practices showed clear benefits: they reduced stress, and sleep disturbances, hot flashes and fatigue showed improvement. Depression was also marginally reduced. There were 19 proinflammatory genes that had been turned off, but not in the control group that did not do mindful practices. Tests for changed genes revealed that transcription factor NF-κB was significantly downregulated. Conversely the anti-inflammatory glucocorticoid receptor and the interferon regulatory factors were increased. Downregulated genes were shown to come from monocytes and dendritic cells while the upregulated genes came from B lymphocytes.

9.  Telomerase gene expression

Lifestyle modification changes telomerase gene expression: 48 patients with high blood pressure were enrolled either in an extensive lifestyle program teaching them about losing weight, eating less sodium, exercising, adopting a healthy diet and drinking less alcohol; the other choice was to use transcendental meditation (TM) combined with health education with weekly sessions for 4 months. It turned out that both programs led to an increased expression of telomerase genes. Both groups did not show telomerase changes, but the authors stated that the observation time was too short for that to occur. The extensive health education program turned out to be better for patients with high blood pressure as it decreased the diastolic blood pressure more and resulted in healthier lifestyles.

10. Older patients with insomnia

Mind-body interventions for older patients with insomnia: A sample of 120 older adults with insomnia was divided into two groups. One group was treated with cognitive-behavioral therapy (CBT), the other group with Tai Chi. The control group consisted of a group of people participating in a sleep seminar. 4 months after the intervention the CBT group had a significantly reduced C-reactive protein (CRP). The proinflammatory markers were reduced in both groups after 2 months and in the Tai Chi group this remained low until 16 months. Gene expression profiling showed that CBT downregulated 347 genes and upregulated 191 genes; the Tai Chi group had downregulated 202 genes and upregulated 52 genes. The downregulated genes were mostly inflammatory genes while the upregulated genes controlled mostly interferon and antibody responses.

11. Patients with bowel disease

19 patients with irritable bowel syndrome (IBS) and 29 patients with inflammatory bowel disease (IBD) were treated with a relaxation response-based mind-body intervention. This consisted of 9 weekly meetings, each lasting 1.5 hours and practices a home for 15-20 minutes. The participants were taught breathing exercises and cognitive skills designed to help manage stress. At the end of the mind-body intervention and at a follow-up visit 3 weeks later participants of both the IBS and IBD groups scored higher in quality of life and lower in the level of anxiety they had before. They had reduced symptoms of their conditions. The IBS group showed an improvement in 1059 genes. These were mostly improvements in inflammatory responses, in cell growth, regarding proliferation, and also improvements in oxidative stress-related pathways. The IBD group showed improvements in 119 genes that were related to cell cycle regulation and DNA damages. Other genetic tests showed that NF-κB was a key molecule for both IBS and IBD. The main finding was that relaxation response-based mind-body intervention was able to down regulate inflammation in both IBD and IBS.

12. Caregivers for Alzheimer’s patients receiving a course of MBSR

A course of mindfulness based stress reduction (MBSR) was given to a group of 25 caregivers. Using 194 differently expressed genes the investigators could predict who would be a poor, moderate or good responder to the MBSR intervention. These genes related to inflammation, depression and stress response. 91 genes could identify with an accuracy of 94.7% at baseline whether the person would receive psychological benefits from the MBSR program.

13. Higher state of consciousness in two experienced Buddha meditators

Genetic test showed, similar to the other cases described here that genes involved in the immune system, cell death and the stress response were stimulated. EEG studies in both individuals during deep meditation were almost identical with an increase of theta and alpha frequency ranges.

14. Rapid gene expression in immune cells (lymphocytes) in the blood

One study used gentle yoga postures, meditation and breathing exercises. 10 participants who were recruited at a yoga camp had yoga experience between 1.5 months and 5 years. Their response resulted in 3-fold more gene changes than that of controls. Otherwise the findings were very similar to the other studies.

15. Genomic changes with the relaxation response

The relaxation response (RR) is the opposite of the stress response.  One study examined how various modes of entering into the relaxation response like yoga, Qi Gong, Tai Chi, breathing exercises, progressive muscle relaxation, meditation, and repetitive prayer would lead to beneficial gene effects. As in other studies inflammation was reduced and the immune system was stimulated from the relaxation response. This was verified with detailed gene studies. The authors noted that different genes were activated in people who had done long-term RR practice versus people who practiced RR only for a shorter time. There were distinctly different gene expressions.

16.  Energy metabolism and inflammation control

Relaxation responses beneficial for energy metabolism and inflammation control: Experts with experience in RR were compared with a group of novice RR practitioners. Experts and short-term practitioners expressed their genes differently at baseline. But after relaxation both experts and novices had gene changes in the area of energy metabolism, electron transport within the mitochondria, insulin secretion and cell aging. The upregulated genes are responsible for ATP synthase and insulin production. ATP synthase is responsible for energy production in the mitochondria and down regulates NF-κB pathway genes. Inflammation was reduced by these changes. All these beneficial gene changes were more prominent in expert RR practitioners. Other beneficial changes noted were telomere maintenance and nitric oxide production in both expert and novice RR practitioners.

17. Relaxation changes stress recovery and silences two inflammatory genes

Mindfulness meditation changes stress recovery and silences two inflammatory genes: Experienced meditators were tested after an intensive 8-h mindfulness meditation retreat workshop. Two inflammatory genes were silenced by mindfulness meditation compared to controls. Other genes that are involved in gene regulation were found to be downregulated as well. These experienced meditators had a faster cortisol recovery to social stress compared to controls.

18. Vacation and meditation effect on healing from disease

This last study investigated the effect of a 6-day holiday retreat. One group was offered a 4-day meditation course, one group was the control group just holidaying and the third group was an experienced meditation group who also took the retreat meditation course. Depression, stress, vitality, and mindfulness were measured with questionnaires. All groups were positively changed after the holiday and remained this way at 1 month after the retreat. 10 months after the retreat novice meditators were less depressed than the vacation control group. At the center of the experiment was the gene expression study. 390 genes had changed in all of the groups. The authors assumed that this was due to the relaxation experience of the retreat. The genes involved related to the stress response, wound healing, and injury. Other genes measured inflammation (control of tumor necrosis factor alpha). Another set of genes measured the control of protein synthesis of amyloid beta (Aβ) metabolism, which causes Alzheimer’s disease and dementia. All groups had markers that indicated less risk of dementia, depression and mortality, which was likely due to the relaxation from the retreat.

Relaxation Reduces Inflammation

Relaxation Reduces Inflammation

Conclusion

This study is a meta-analysis of 18 research papers. The authors found that very different approaches to relax the mind have fairly consistent universal effects on reducing inflammation. Most of this work was done with genetic markers. No matter what type of relaxation method you use, you will have beneficial effects from it. But the beneficial effect is not only strengthening the immune system, it also improves sleep, depression, anxiety and blood pressure. In addition it is improving your stress response, wound healing, risk of dementia and it reduces mortality. We don’t quite understand all of the details yet.

What is definitely documented is the effect of the mind-body interaction. It also points clearly to the relaxation response from meditation and similar relaxation methods. This has been proven beyond any doubt through genetic tests.

May
20
2017

Prevention Of Telomere Shortening

Dr. Mark Rosenberg gave a talk on prevention of telomere shortening. This was presented at the 24th Annual World Congress on Anti-Aging Medicine (Dec. 9-11, 2016) in Las Vegas that I attended. The detailed title was: “The Clinical Value of Telomere Testing”.

What are telomeres?

Telomeres are the caps at the end of chromosomes. They are very important in the aging process. Prematurely shortened telomeres are linked closely to all major diseases like cardiovascular disease, cancer, diabetes and more. Telomeres are also a measure of the aging process. Aging occurs due to a decrease of the number of cells in organs and/or because of a lack of functioning of these organs. Telomeres get shortened every time a cell divides. But when the telomeres are used up, there comes a time when cells can no longer divide. These cells become senescent cells or they enter apoptosis (programmed cell death).

The senescent cells can become a problem when they get transformed into cancer cells and their telomeres lengthen again. These cancer cells divide rapidly and this can become the reason why cancer patients to die.

What is the significance of telomeres?

Telomere dysfunction is the first sign that the telomeres are getting shorter in a person compared to the average telomere length in a comparable age group. This is not only important for aging, but also has clinical implications. The shorter telomeres are, the higher the risk for cardiovascular disease. Telomere length also provides prognostic information about the mortality risk (risk of dying) with type 2 diabetes and for many cancers. Many physicians incorporate a telomere blood test into periodic health checks, if the patient can afford it.

Interventions that help telomere length

Here are a number of things we can do to lengthen our telomeres.

  1. Rosenberg mentioned that the strongest effect on telomere lengthening comes from caloric restriction and weight loss. 80 years ago they showed at the Cornell University that rats put on calorie restriction had a 30% increase in their mean and maximum lifespan. Many research papers have confirmed that the same is true in man and that the common denominator is telomere lengthening.
  2. Next are regular physical activity, meditation, reduction of alcohol consumption and stopping to smoke.
  3. Taking antioxidants and omega-3 fatty acids regularly will also lengthen telomeres.
  4. Improving one’s dietary pattern by adopting a Mediterranean type diet that contains cold-pressed, virgin olive oil.
  5. Telomerase activators. Here is some background on the TA-65 telomerase activator, which is based on Chinese medicine. A one year trial was completed with 250 units and 1000 units of TA-65 per day. The lower dose (250 units) showed effective telomere lengthening, while the placebo dose did not. The 1000 unit dose did not show statistical significance.

Should you wish to take TA-65, only take 250 units per day, not more.

Cancer and telomeres

There is a strong correlation between cancer and telomere shortening. When cells are at the brink of dying toward the end of their life cycle the telomeres get shorter and shorter. This is the point where the cells can turn malignant. Certain genetic abnormalities help the malignant transformation, like 11q or 17q deletions or a p53-dependent apoptosis response. Once cancer cells have established themselves they activate telomerase in 85% of cases. In the remaining 15% of cancer cases telomeres are activated through telomerase-independent mechanisms. Here are a few examples.

CLL

CLL stands for chronic lymphocytic leukemia. It is a disease of the aging population. At age 90 people’s bone marrow cells have a telomere length of only 50% of the length at birth. This is the reason that in older age CLL is more common. Researchers observed a population segment and found that the shorter telomeres were, the poorer the overall prognosis and overall survival for CLL was.

Lung cancer

In patients with non-small cell lung cancer the telomerase activity was examined. When telomerase activity was present, the 5-year survival was only 55%. When telomerase activity was absent, the prognosis was 90% survival after 5 years.

Prostate cancer

  1. Telomere shortening in stromal cells was found to be associated with prostate cancer risk. Men with shorter telomere length in stromal cells had a 266% higher risk of death compared to men with normal telomere length.
  2. Another study took blood samples and determined the telomere length in lymphocytes (the immune cells). Those men who came down with prostate cancer within a year after the blood sample was taken had short telomeres. The risk for prostate cancer in these patients was 355% higher than in the prostate cancer negative controls.

Yet another study looked at surgical tissue samples from 596 men that

Underwent surgery for clinically localized prostate cancer. Patients whose samples showed variable telomere lengths in prostate cancer cells and shorter telomeres compared to prostate samples with less variable telomere length and longer telomeres had a much poorer prognosis. They had 8-times the risk to progress to lethal prostate cancer. And they had 14-times the risk of dying from their prostate cancer.

Breast cancer

Breast cancer is diverse and consists of cases that are genetically inherited (BRCA1 and BRCA2), but there are also cases where the cancer is local or more advanced (staging). In families with mutated BRCA1 and BRCA2 telomeres are significantly shorter than in spontaneous breast cancer. Increased telomerase activity in breast cancer cases is directly related to how invasive and aggressive the breast cancer is.

  1. One study was shown where blood leukocytes were analyzed for telomere length in 52 patients with breast cancer versus 47 control patients. Average telomere length was significantly shorter in patients with a more advanced stage of breast cancer than in early breast cancer. Mutated HER patients had the shortest telomeres. It follows from this that checking for the HER status and blood telomere testing adds to the knowledge of potential cancer development and prognosis.
  2. Short telomere length was associated with larger breast tumors, more lymph node metastases and more vascular invasion. More aggressive breast cancer cells have higher telomerase activity. More than 90% of triple negative breast cancers have short telomeres.

CNS disorders and telomeres

Dr. Rosenberg presented evidence that shorter telomeres are associated with dementia. But dementias with Lewy bodies and Alzheimer’s disease are also linked to short leukocyte telomeres. The length of blood telomeres predicts how well stroke patients will do and how people with depression will respond to antidepressants.

Cardiovascular disease and telomeres

Our blood pressure is kept constant through the renin-angiotensin-aldosterone system. When this system is not stable, our blood pressure shoots up and causes cardiovascular disease. This is tough for the heart, as it has to pump harder against a higher-pressure gradient. A study of 1203 individuals was examining the connection between leukocyte telomere length and renin, aldosterone and angiotensin II activity. It concluded that oxidative stress and inflammatory responses affect the telomere length of leukocytes and that the more stress there is in the renin-angiotensin-aldosterone system, the more cardiovascular disease develops. The conclusion of the study was that the overall cardiovascular stress leads to shortening of leukocyte telomeres.

Prevention Of Telomere Shortening

Prevention Of Telomere Shortening

Conclusion

Telomere length testing from a simple blood test will become a more important test in the future as hopefully the cost comes down (currently about 300$). It can predict the general aging status by comparing a single case to the general telomere length of the public. But it can also predict the cancer risk, risk for mental disease and cognitive deficits (Alzheimer’s disease). In addition your cardiovascular status is also globally assessed with this test. What can be done, if the test comes back with short telomeres?

It allows you to change your lifestyle and adopt a healthy diet. You can exercise regularly, take antioxidants and meditate. There are even telomerase activators that are gradually becoming more known. They lengthen the telomeres. The cost of telomerase activators will likely still be a problem for some time. All in all telomere length tests are here to stay, but effective intervention at this point is largely limited to healthy lifestyle choices. This is good news: healthy lifestyle choices like non-smoking, exercise and avoiding non-processed foods are either free or have a reasonable price tag. Telomerase activators are big business and at this point not really affordable!

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Apr
29
2017

Cancer By Chance

A new theory talks about cancer by chance. In other words, it likely is mostly bad luck when cancer develops. Mathematician Cristian Tomasetti and cancer geneticist Bert Vogelstein of Johns Hopkins University in Baltimore, Maryland developed a new model of cancer development. They found that stem cells in different organ systems divide at different rates. The faster they go through cycles of cell divisions, the higher the chances of a mutation. The mutations happen in the genetic material and can lead to cancer. Dr. Vogelstein applied this model to 32 different cancer types and found the following.

  • 66% of cancers: cancer-promoting mutations develop by chance during cell division in various organs
  • 29% of cancers are due to environmental causes
  • 5% of cancers are inherited

Stem cells in organs can turn into cancer by chance

Key to the new theory of “cancer by chance” is that cancer likely is developing from stem cells in different organs. Different stem cells have different rates of stem cell divisions.

In pancreatic cancer they found that 5% were inherited, 18% were from environmental factors (smoking) and 77% came from chance mutations. This data was derived from the Cancer Research UK database.

For prostate cancer the rate of spontaneous mutations is 95%. When all of the cancers are looked at about 1/3 of cancers are due to either environmental or inherited factors, but 2/3 of all cancers are due to random mutations (“bad luck mutations”). They pointed out this fact in their first publication.

With the second publication, as mentioned in the beginning, Vogelstein and Tomasetti concentrated on 17 common cancers in 69 countries. They searched 423 international cancer databases. Again they found that the more stem cells divided in an organ, the more random mutations occurred. This caused cancers in that organ.

Here are a few examples for lifetime stem cell divisions:

  • Colon: 6,000 cell divisions in stem cells of the colon
  • Breast: 300 cell divisions in breast stem cells
  • Lung: only 6 cell divisions in lung stem cells

Colon cancer is very common because of the high stem cell division rate. But they also looked at environmental factors. For instance, lung cancer is rare in non-smokers because stem cells in lungs divide slowly. However, the carcinogens from cigarette smoke add a huge environmental risk. The end result: there is more lung cancer in smokers. Vogelstein said that with every stem cell division there is the creation of three new cell mutations because the body has a “poor copying machine”. During meiosis DNA breaks can occur that lead to mutations. Once they occurred, they continue to get copied.

Environmental factors versus cancer by chance

In the first paper the medical community was critical about how the authors had overemphasized that two third of cancer is caused randomly. So in the second paper Vogelstein and Tomasetti mentioned quite a bit how a change of the environment can change the final outcome of developing cancer.

This is also reflected in this summary from the CNN.

They mentioned that one mutation is not enough to cause cancer. You need three or four such mutations. As we get older there is a higher likelihood that we accumulate this number of mutations, and cancer can develop. But if we exercise, stop smoking and avoid red meat, this can contribute to a much healthier environment in the dividing stem cells. In this case we may not accumulate enough stem cell mutations in our lifetime to come down with cancer.

There is a problem with prostate cancer as indicated in this German summary of Vogelstein and Tomasetti’s work.

Japanese men have an extremely low rate of prostate cancer, namely 1/25th of the rate in the US. When Japanese men immigrate to the US, it does not take long before their risk is the same as that of US men. This is a classical case of the importance of environmental factors in cancer causation. Song Wu has pointed out in a publication in Nature that in his opinion Vogelstein and Tomasetti did not pay enough attention to extrinsic (environmental) factors in the causation of cancers.

This could explain the prostate cancer conundrum just mentioned. There may be more xenoestrogens in the environment in the US when compared to Japan, and this may have caused the additional prostate cancers when Japanese men moved to the US. Xenoestrogens are estrogen-like hormones in the environment, which can cause prostate cancer.

Prevention undermines “cancer by chance”

The role of prevention is likely larger than previously estimated. Now that we know that on average 2/3 of all cancers are due to chance mutations, it is important to realize that prevention and early detection play an enormous role.

  1. Most cancers can only be cured in stage 1 and stage 2 out of 4 stages. And this is only the case when the mutated stem cells are removed along with the clone of cancer cells.
  2. In terms of reducing the risk for lung cancer this means to stop smoking.
  3. With colon cancer it means having regular colonoscopies where the suspicious polyps are removed.
  4. For prostate cancer it means to do a mapping biopsy and to do cryoablation therapy, which has a prostate cancer vaccination effect as well.
  5. Not all cancers can be diagnosed early. Pancreatic cancer is such a difficult to diagnose cancer. But screening methods have been developed that are more sensitive and very specific such as the Oncoblot test.  With this test even cancer of the pancreas can be diagnosed years before it would be clinically detectable.
  1. We do know that chronic inflammation can lead to cancer. It makes sense therefore to start with an anti-inflammatory diet like the Mediterranean diet. Fish oil is also anti-inflammatory.
  2. Add to this regular exercise, as we know it reduces the risk for cancer development and strengthens your heart and lungs.
  3. Vitamin D3 can reduce cancer risks in both males and females. When vitamin D3 was given and blood 25-hydroxyvitamin D levels were above 40 ng/ml, the breast cancer rate was reduced by 71% compared to a low vitamin D3 group. Similarly in men the prostate cancer rate dropped by 71% with vitamin D3 supplementation.  There is more good news with vitamin D3. You can read about it in the link.
Cancer By Chance

Cancer By Chance

Conclusion

The causes of cancer have always been by chance, by environmental exposure and by inheritance. In recent years more detail about this has come to the forefront. Now we know that the majority of cancers develop by chance, but this does not mean we should sit back and do nothing. The PAP test with early diagnosis of cancer of the cervix and early treatment has almost eradicated this cancer. HPV vaccinations have added to the armamentarium. Colonoscopies have reduced the incidence of colon cancer, but only through screening at regular intervals. The PSA test has enabled men to check for prostate cancer, and early treatment for this is quite successful. More is known about cancer prevention through supplements and lifestyle.

Nature is cruel and wants to knock us off, as we get older. The only alternative we have is to fight back as follows: reducing environmental causes, increasing preventative steps and going for early treatment, when cancer is diagnosed.

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Apr
08
2017

Breast Cancer Risks

Dr. David Zava, PhD gave a talk on breast cancer risks. This was presented at the 24th Annual World Congress on Anti-Aging Medicine (Dec. 9-11, 2016) in Las Vegas that I attended. The detailed title was: “The Role of Hormones, Essential Nutrients, Environmental Toxins, and Lifestyle Choices on Breast Cancer Risk”.

He pointed out that both estrogens and progesterone are safe hormones, as long as they are not overdosed and they are balanced. Unfortunately many women in menopause have too much estrogen on board as the ovaries are still producing them, but there is a lack of progesterone, the moderating hormone that makes estrogen safe.

In the following I am summarizing Dr. Zava’s talk with regard to the essential messages, but leaving away much of the highly technical detail that was presented as this would dilute the message of this blog. I will include a few links for those who are inclined to read more details about the topic.

Balance between estrogen and progesterone

Most of her life a woman is used to cyclical hormone changes between estrogen and progesterone. When a woman no longer ovulates in premenopause and menopause there is a surplus of estrogen and a lack of progesterone. Having no ovulation means that there is no corpus luteum developing, where in the past progesterone was made. This creates a disbalance where estrogen is dominating; it is called “estrogen dominance”.

This is a dangerous hormone disbalance, because the breast ducts are stimulated to grow and the modifying, calming effect of progesterone is missing. Mixed into this is that the stress hormone, cortisol also can make the effect of estrogen worse. On the other hand Dr. Zava showed slides from studies where progesterone was replaced through a skin progesterone cream (percutaneous bioidentical progesterone cream). Plasma and breast tissue concentration of progesterone were measured in 40 premenstrual women. They had been diagnosed with breast lumps and were scheduled for surgery. One group was treated with progesterone cream for 10 to 13 days; the other group was the placebo group. At the time of surgery the plasma (blood) values were unchanged, but progesterone levels in breast tissue were elevated more than 100-fold over the values from the placebo group who had been treated with a neutral skin cream. The same experiment also showed that progesterone reduced the number of proliferating epithelial cells (experimental progesterone group). Estrogen on the other hand was shown to increase the number of proliferating epithelial cells (placebo group).

Another example that Dr. Zava gave was a study where 25 mg of bioidentical progesterone cream applied directly to breasts of premenopausal women increased breast tissue progesterone 100-fold, while blood concentrations of progesterone remained the same. Again breast stimulation by estrogen of normal epithelium cells was decreased by progesterone.

How to measure progesterone levels

Dr. Zava who runs the ZRT laboratory spent some time to explain how to measure progesterone in a physiological way. He said that these experiments and others that he also projected tell a clear story. Blood (serum) progesterone levels do not adequately reflect what tissue levels in a woman’s breasts are. On the other hand saliva hormone levels do give an accurate account of what breast tissue levels are like. A woman received 30 mg of topical progesterone application. She then had hourly progesterone levels in the serum and in the saliva done. The serum progesterone levels remained at around 2 ng/ml, while the saliva progesterone levels peaked 3 to 5 hours after the application. It reached 16 ng/ml in saliva, which also represents the breast tissue progesterone level. Dr. Zava said that the important lesson to learn from this is not to trust blood progesterone levels. Too many physicians fall into this trap and order too much progesterone cream, which leads to overdosing progesterone. With salivary progesterone levels you see the physiological tissue levels, with blood tests you don’t. Dr. Zava said: avoid using venipuncture blood or urine in an attempt to interpret hormone test levels, as you will underestimate bio-potency and overdose the patient.

Historical failure of estrogen replacement therapy (ERT)

A review of breast cancer would not be complete without mentioning the Women’s Health Initiative (WHI). The U.S. National Institutes of Health (NIH) initiated this trial in 1991.

  1. The WHI ended suddenly in July 2002. The authors stated: “The overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2 year follow-up among healthy postmenopausal US women.” The study found a 41% increase in strokes, 29% increase in heart attacks, 26% increase in breast cancer, 22% increase in total cardiovascular disease, a doubling of blood clots. The recommendation made by this study was to discontinue PremPro.
  2. Another study that was mentioned was “Breast cancer and hormone-replacement therapy in the Million Women Study”.  In this study postmenopausal women were given HRT with synthetic hormones, either estrogen alone or estrogen mixed with a progestin (in British English “progestagen”. After 5 years estrogen alone was associated with a 30% increased risk of developing breast cancer. HRT with an estrogen-progestagen mix was associated with a 100% increased risk of developing breast cancer.
  3. Unfortunately in both of these human experiments the wrong hormone substances were used, namely synthetic estrogens and synthetic progestins. They are NOT identical with natural estrogens and progesterone that a woman’s body makes. As long as the hormones used for hormone replacement therapy are chemically identical to the natural hormones, the body will accept them as they fit the natural hormone receptors in the body. It is the misfit of synthetic hormones that blocks the estrogen receptors or the progesterone receptors. You can readily see from the illustrations of this link that there is a fine balance between the workings of these receptors and there is absolutely no room for patented side chains that Big Pharma introduced into synthetic HRT hormones. The other problem of both these studies was that every woman was getting the same dose of hormones and that nobody measured their estrogen blood or estrogen saliva hormone levels. In retrospect the regulatory agencies should never have allowed these “hormones” to hit the market.

Breast cancer develops in three stages

Dr. Zava explained that it has been known for some time that there are 3 stages involved in the development of breast cancer.

  1. Initiation

Damage to the DNA of one of the cells types in the breast is what starts the process in the development of breast cancer. This can be done by catechol estrogen-3,4-quinones as was shown by these researchers.

Aromatase inhibitors can be used to reduce estrogen in overweight or obese women where aromatase is present in fatty tissue. The reason obese women have more breast cancer is likely from the extra estrogen production from androgens, male hormones produced in the adrenal glands that get converted by aromatase into estrogen.

Iodine/iodide has been shown to alter gene expression, which reduces breast cancer development, but also slows down cell division in existing breast cancer. The authors suggested to use iodine/iodide supplements as adjuvant therapy in breast cancer treatment.

  1. Promotion

The next step is that something has to promote the DNA mutation into becoming part of a cancer cell. Estrogen quinones are dangerous estrogen metabolites. They can form from catechol estrogens (other metabolites of estrogen) by reactive oxygen species. But selenium, a trace mineral can interrupt the formation of estrogen quinones, which stops the breasts cancer promotion process. A study from the Klang Valley, Malaysia showed that selenium showed a dose-response effect with respect to prevention of breast cancer; the more selenium in the food, the less breast cancer occurred.

  1. Progression (includes invasion and metastases)

Several factors can help the breast cancer cells to progress, grow bigger locally and eventually move into other areas of the body as metastases. Dr. Zava showed several slides where details of metabolic processes were shown and how changes in some of these would lead to progression of breast cancer. Estrogen excess is a common pathway to breast cancer. The key is to balance it with progesterone, supplements, remove anything that causes estrogen overproduction like obesity (via the aromatase pathway).

The fallacy of overdosing or underdosing

When estrogen is overdosed, it becomes aggressive as indicated before; it can initiate DNA mutations that can cause breast cancer. If it is under dosed, the lack of estrogen can cause heart attacks, strokes and osteoporosis. When estrogen is balanced with progesterone a postmenopausal woman feels best and she is protected from the negative effects of estrogen.

Measures that help prevent breast cancer

  1. When supplementing with bioidentical hormones, keep estrogen within physiological limits and don’t overdose. This can be measured through blood tests or saliva hormone tests. Your most important natural opponent of estrogen is progesterone, which is usually missing in menopause. Measure hormones using tests (progesterone only with saliva tests, estrogen either by blood tests or saliva tests). Don’t rely going by symptoms.
  2. Keep the progesterone to estrogen ratio (Pg/E2) at an optimal range, which is in the 100- to 500-fold range. Measure the saliva hormone level of both progesterone and estrogen and calculate. Remember that progesterone serum levels are meaningless. The much higher progesterone level protects the postmenopausal woman from estrogen side effects. Here is a statement worth noting: “Until evidence is found to the contrary, bioidentical hormones remain the preferred method of HRT.” This was the conclusion of a study using bioidentical hormones, where the protection from breast cancer and heart attacks and strokes was also noted.
  3. Increase fiber intake and reduce red meat consumption. This will eliminate conjugated steroid hormones in the stool. It also increases the sex hormone binding globulin in the blood, which limits the bioavailability of estrogens. Fiber absorbs bile toxins and removes them from the body.
  4. Calcium-D-glucarate is a supplement that will decrease beta-glucuronidase. The estrogens were conjugated with the purpose to be eliminated, but beta-glucuronidase causes the conjugated estrogens to be reabsorbed.
  5. Probiotics likely stimulate the immune system and help reduce the risk of breast cancer.
  6. Avoid toxins like petrochemical pollutants and toxic chemicals. Avoid trans fats. If toxic, heavy metals are present (arsenic, cadmium, lead, mercury) remove these. Some naturopaths use EDTA chelation to do this.
  7. Supplements: sulforaphane (broccoli), EGCG (green tea), alpha-lipoic acid (antioxidant), cruciferous vegetables, resveratrol, selenium and iodide/iodine, N-acetyl cysteine-glutathione. All these supplements/nutrients will prevent estrogen to go to the “dark side”. The dark side is the formation of toxic 4-OH estrogen that could further be converted into catechol estrogen-3,4-quinones that can damage DNA and cause mutations.
  8. Increase methylation of catechol estrogens: vitamin B1, B6, B12 and folic acid. Methyl donors also are useful for this purpose: MSM (methylsulfonylmethane), SAMe, and Betaine.
  9. Improve your diet (Mediterranean type), exercise moderately, reduce stress, and replace hormones in physiological doses as discussed under point 1 and 2.
Breast Cancer Risks

Breast Cancer Risks

Conclusion

Dr. David Zava, PhD gave an interesting talk at the 24th Annual World Congress on Anti-Aging Medicine (Dec. 9-11, 2016) in Las Vegas that I attended. It became clear that estrogens, when unopposed by enough progesterone, could cause mutations in breast tissue of women and cause breast cancer. He also reviewed two major clinical trials where hormone replacement therapy (HRT) was used. The problems with these were the synthetic estrogen hormones that caused breast cancer and the synthetic progestins that also behaved like estrogens (not like progesterone) and caused even more breast cancer. The lesson to be learnt from this is that only bioidentical estrogens and progesterone can be used in hormone replacement for menopause. Also, the hormones must be balanced as discussed under point 2 of measures that help to prevent breast cancer. In addition there was a list of other useful supplements given that can be taken to reduce the danger of breast cancer.

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Mar
11
2017

Obesity And Diabetes Can Cause Cancer

Dr. Nalini Chilkov gave a talk about how obesity and diabetes can cause cancer. The original title was “Integrative Cancer Care, Increased Rates of Cancer and Cancer Mortality Associated with Obesity and Insulin Resistance, Nutraceutical and Botanical Interventions”. Her talk was presented at the 24th Annual World Congress on Anti-Aging Medicine (Dec. 9-11, 2016) in Las Vegas that I attended.

In the following I will present a brief summary of her lecture.

Obesity is a major risk factor for cancer

Obesity causes 14% of all cancer deaths in men and 20% of cancer deaths in women.  This link explains this in more detail. The following 15 cancers were linked to obesity in terms of causation. They are: colon cancer, gastric cancer, gallbladder cancer, ovarian cancer, breast cancer, liver cancer, uterine cancer, endometrial cancer, rectal cancer, pancreatic cancer, cervical cancer, non-Hodgkin’s lymphoma, renal cancer, multiple myeloma and esophageal cancer.

The American Society of Clinical Oncology reported about a meta-analysis involving 82 studies. This involved more than 200,000 women with breast cancer. Premenopausal and postmenopausal women were compared who were obese or normal weight. Premenopausal, obese breast cancer women had a 75% increase in mortality compared to the normal weight breast cancer group. With postmenopausal, obese breast cancer women there was a 34% increase of mortality compared to the normal weight group.

With obese prostate cancer patients there is a similar observation. Obese patients have a more aggressive prostate cancer on the Gleason score and the cancer is in a more advanced stage at the time of diagnosis.

Diabetes increases mortality from cancer

Obesity is a common risk factor for both cancer and diabetes. But diabetes by itself is also increasing mortality of several cancers. In a consensus report details of the relationship between cancer and diabetes have been discussed in detail. The following cancers have been identified to have an increased risk of diabetes: pancreatic, gastric, esophageal, colorectal, liver, gallbladder, breast, ovarian, endometrial, cervical, urinary bladder, renal, multiple myeloma and non-Hodgkin’s lymphoma.

A meta-analysis suggests that cancer patients who are diabetic have a 1.41-fold increased risk of dying compared to those cancer patients who have normal blood sugars. Dr. Chilkov explained in detail what the various mechanism are that account for the faster cancer growth in obese and diabetic patients. High insulin levels is one of the risk factors, so is IGF-1, an insulin-like growth factor. The aromatase enzyme in fatty tissue turns male type hormones into estrogen, which also can stimulate cancer growth.

Carbohydrate restriction diet to prevent obesity

Low carb diets like the Mediterranean diet, the ketogenic diet and the Atkins diet will drop blood insulin and lactate levels. Cancer size and cancer growth are related to insulin and lactate levels. A low carb diet can reduce insulin-mediated uptake of sugar into cancer cells.

Research has shown that cancer metabolism slows down when a 10%-20% carb/high protein diet is consumed by the patient. This reduces the amount of sugar that is taken up by cancer cells. It also reduces insulin, so there is less cancer growth. A ketogenic diet is a more strict way to restrict carbohydrates. Intermittent fasting is also a useful method to reduce carbohydrate intake.

Here is an interesting study that illustrates the power of intermittent fasting. The study involved 2413 patients with early breast cancer who were followed for 7 years. Those breast cancer patients, who consistently did not eat anything between dinner and breakfast for 13 hours or more, had a 36% lower risk of having a cancer recurrence. There was also a 21% lower risk of dying from breast cancer when fasting was done for 13 hours or more overnight.

Supplements to prevent obesity, diabetes and cancer

A low carb diet and in some cases even a ketogenic diet is beneficial as a baseline. A regular exercise program is also useful for general fitness building and cardiovascular strengthening. In addition Dr. Chilkov recommended the following supplements.

  1. To reduce inflammation in the body, Dr. Chilkov recommended taking 2000 to 6000 mg of omega-3 fatty acids per day (molecularly distilled fish oil).
  2. Berberine 500 to 1000 mg three times daily. Dr. Chilkov said that Berberine has anti-cancer properties, improves insulin sensitivity and reduces absorption of sugars in the intestinal tract.
  3. Curcumin inhibits cancer cell division, invasion and metastatic spread through interaction with multiple cell signaling proteins. Several researchers showed that curcumin could lower blood sugar levels by stimulating insulin production from beta cells in the pancreas. Triglycerides, leptins and inflammation in fat cells are also lowered by curcumin. Insulin sensitivity increases through the action of curcumin. Dr. Chilkov recommended 300 mg/day of curcumin for 3 months.
  4. Resveratrol, the bioflavonoid from red wine is a powerful anti-inflammatory. This antioxidant has several other effects, which make it challenging to measure each effect by itself. This group of investigators managed to simultaneously measure these effects. They found that resveratrol lowered the C-reactive protein by 26% and tumor necrosis factor-alpha by 19.8%. Resveratrol also decreased fasting blood sugar and insulin; in addition it reduced hemoglobin A1C and insulin resistance. The recommended daily dose of resveratrol is 1000 to 5000 mg.
  5. Green tea catechins (EGCG) help to normalize the glucose and insulin metabolism. The dosage recommended was 1-3 grams per day.
  6. Reishi mushroom (Ganoderma lucidum) contain polysaccharides with antidiabetic and antiobesity effects. They make gut bacteria produce three types of short-chain fatty acids that control body weight and insulin sensitivity.
Obesity And Diabetes Can Cause Cancer

Obesity And Diabetes Can Cause Cancer

Conclusion

Obesity is a risk factor not only for diabetes, but also for cancer. Chronically elevated blood sugars, increased fasting insulin levels and increased IGF1 levels can cause cancer. In addition they can stimulate tumor growth and increase cancer mortality. It is for this reason that the health care provider should screen all diabetics for cancer. In her talk Dr. Nalini Chilkov gave clear guidelines what supplements will be beneficial to reduce the risk of obesity and diabetes as well as cancer. Start with a healthy, balanced diet. Add an exercise program. Then consider some of the above-mentioned supplements to reduce your risk for cancer, diabetes and obesity.

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Jan
02
2017

Gut Bacteria Can Protect Your Brain

The neurologist, Dr. David Perlmutter gave a keynote address where he pointed out that gut bacteria can protect your brain. The topic of his actual talk was “Rewrite your brain’s destiny” and the venue was the 24th Annual World Congress on Anti-Aging Medicine (Dec. 9-11, 2016) in Las Vegas. Many of the talks centered around the gut microbiome. In this talk Dr. Perlmutter stressed the fact that the right mix of gut bacteria will protect your brain, while the wrong mix can make you sick. There were many slides, but too much information to mention all of details of the talk here. I will summarize the broad outline of Dr. Perlmutter’s presentation and emphasize the practical implications this has for everyday life to prevent degenerative brain diseases.

A few facts

  1. Did you know that the brain uses 25% of the body’s energy, but has only a 3% of the body’s weight?
  2. The gut flora has trillions of gut bacteria with its own DNA material. 99% of the DNA material in our body comes from the gut bacteria and the bacteria on our skin surface; only 1% of the entire DNA in the body is your own DNA. We are eating for 100 trillion bacteria, but if they are good bacteria they provide us with important vitamins and they produce molecules that stimulate our immune system.
  3. This means we better have bacteria in our guts that are friendly, not the bad bacteria that can cause us problems. An Italian study determined the gut flora of children in central Africa (Burkina Faso) and compared the gut flora to children from developed countries in Europe. There was a significant difference with the African children having a healthy microbiome in the gut and the children from developed Europe having unhealthy gut bacteria. This is important new information. Many other research papers have established that leaky gut syndrome and autoimmune diseases are linked to dysbiosis, which is the name for the unhealthy microbiome in the gut.

Chronic inflammation

Dr. Perlmutter showed several slides where literature was cited showing that chronic inflammation in the civilized world is increasing. He also showed that dysbiosis (unhealthy gut bacteria taking over) is also increasing. On several slides Dr. Perlmutter showed that in civilized countries like Iceland, Denmark, Germany, the US, Japan and others the bacterial diversity of the gut bacteria in people was vastly reduced compared to the diversity of gut bacteria of people in Kenya, Ethiopia, Nigeria or rural India. The same countries that have diminished gut bacterial diversity (dysbiosis) also have the highest prevalence of Alzheimer’s disease. On the other hand the same countries with diverse gut bacteria have a low incidence of Alzheimer’s disease. When infestation with parasites was examined there was also a parallel between increased parasitic stress and low Alzheimer’s disease rates, again in countries like Kenya, Ethiopia, Nigeria or rural India. The same countries where gut dysbiosis was present the parasitic infestation was low.

Further research has established that gut dysbiosis leads to an inflammatory condition of the gut where lipopolysaccharides (LPS) from gut bacteria are absorbed causing inflammatory reactions within the body.

At the same time this leaky gut syndrome can cause obesity and leakage in the gut/brain barrier as indicated in this link. The result is neuroinflammation, cognitive impairment and vulnerability to develop Alzheimer’s disease. Our most dreaded brain diseases come from inflammation: Alzheimer’s, Parkinson’s disease, autism, multiple sclerosis etc. These are degenerative brain disorders due to chronic inflammation. If you eat a lot of red meat, sausages and processed foods your gut microbiome will undergo negative changes. If you eat healthy food with lots of vegetables, fruit and you cut out sugar and too many starches, you have a healthy microbiome, which develops a robust immune system. We have to rethink the gut/brain connection and learn how to prevent these chronic illnesses.

Obesity and gut dysbiosis

In the link above it was shown that obesity is associated with inflammation. It was also shown with MRI scans that the part in the brain, called hippocampus was shriveled up (atrophied). This is a typical sign of dementia and Alzheimer’s disease. The investigators also confirmed with mental health functional tests that these patients had cognitive decline.

Another study also noticed that in a group of obese patients the hippocampus part of the brain was shriveled up the more obese people were. Obesity is associated with dysbiosis of the gut flora.

Practical application: the DASH diet and the Mediterranean diet are both healthy, balanced diets, strikingly different from the Standard American diet. In a study the hypothesis was tested whether the DASH diet and the Mediterranean diet would postpone dementia in a group of elderly patients. The answer was: yes, the hypothesis is true.

What does gut dysbiosis do?

It was shown in mice that chronic inflammation of the gut through ingestion of an irritant (dextran sodium sulfate) led to reduced new nerve growth in the hippocampus compared to control animals. It only took 29 days to show a marked difference between experimental and control animals in terms of reduced growth in the nerve cells of the hippocampus, the center of cognitive control.

The negative mediators were inflammatory kinins released from the gut wall and affecting the brain.

Antibiotic treatments and antibiotic residues in milk, milk products, meat, but also in all GMO foods are the irritants of the gut wall in humans. The antibiotics change the gut flora and lead to dysbiosis, which then causes gut wall inflammation and the cascade of events described above. The new finding is that GMO food contains RoundUp (they are “Roundup ready” crops). The herbicide Roundup was originally patented as an antibiotic and still leads to significant dysbiosis. Dr. Perlmutter urged the audience to buy organic food as the only method to reduce our exposure to Roundup. Roundup contributes to causing celiac disease and gluten intolerance in addition to exposure to the modern wheat (Clearfield wheat). The FDA is starting to do testing on foods for Roundup (glyphosate).

If things are sounding bad for Roundup, it only gets worse: Roundup has now been linked to causing cancer. In medicine it usually takes some time before definite action is taken. The agriculture industry is so deeply entrenched in the use of Roundup; I suspect that denial will be the first line of defense. My first line of defense in turn is to stick to organic food.

To sum up: Roundup and the Standard American diet lead to dysbiosis in the gut, which causes leaky gut syndrome. This causes inflammation with the release of cytokines and LPS from the gut wall to the blood. These substances cross the blood/brain barrier and lead to inflammation in the brain. This affects the hippocampus with the classical sign of shrinkage. But Parkinson’s disease, multiple sclerosis, autism in children and Alzheimer’s disease in older people are all caused by chronic inflammation. There are three more brain-related diseases that are related to gut inflammation: stroke, depression and attention deficit hyperactivity disorder (ADHD). Dr. Perlmutter spent some time explaining that antibiotic overuse even leads to an increase of breast cancer as a Danish study has shown. Antibiotic use showed a linear increase of breast cancer as a result of increased antibiotic amounts used. The highest group had a twofold risk compared to a control group with no antibiotic use. Dr. Perlmutter interpreted this to indicate that chronic gut inflammation can even cause a disease like breast cancer.

What can we do to diversify our gut bacteria?

  1. Exercise: A recent study has shown that regular exercise is associated with a diversified gut flora. The reason seems to be the production of butyrate with exercise, which leads to a diversified gut flora. There are reduced LPS levels (lipopolysaccharides from gut bacteria) in people with a higher fitness score.
  2. Eat a DASH diet or the Mediterranean diet as indicated above.
  3. Avoid GMO foods because of the presence of Roundup, which functions like an antibiotic and leads to gut bacteria dysbiosis.
  4. Remember “Antibiotics are weapons of mass microbial destruction”. If you need to take them be careful that you rebuild your gut flora with probiotics. Use of antibiotics increases the risk of type-2 diabetes by 1.53-fold. It also causes a quadrupling of Alzheimer’s disease.
  5. A woman should consider natural childbirth whenever possible, as with a vaginal birth the child is “anointed with gut bacteria”. Vaginally delivered children remain healthier than children delivered by Cesarean section for several years.
  6. Acid-suppressing medications and NSAIDs (anti-inflammatory medication for arthritis) can also lead to dysbiosis. Proton pump inhibitors increase the risk of Alzheimer’s disease by 44%.
  7. Prebiotic fiber can prevent Alzheimer’s. Probiotics do the same.
  8. Avoid sugar: even the Oompa Loompa knew that “If you eat sugar, you get fat” as this YouTube video shows. And obesity is associated with gut dysbiosis with the associated higher risk of degenerative brain diseases.
  9. Take magnesium supplements (250 mg twice per day) and DHA from fish oil capsules. It stabilizes your brain metabolism.
  10. In severe, persistent cases of gut dysbiosis a fecal transplant can be considered by your gastroenterologist. This procedure is done in more than 500 hospitals in the US.
Gut Bacteria Can Protect Your Brain

Gut Bacteria Can Protect Your Brain

Conclusion

The diversity of gut bacteria is immensely important. As discussed, in rural areas of the world there is gut bacteria diversity. In civilized parts of the world dysbiosis of the gut flora frequently occurs. This can lead to gut inflammation and the inflammation eventually gets internalized and can even reach the brain. These are the points to remember: exercise; avoid GMO foods, use prebiotics and probiotics. Avoid antibiotics; also avoid meat from animals that were fed antibiotics for faster growth. Don’t eat processed foods and avoid sugar. A healthy gut creates a healthy body, and this includes a healthy brain as well.

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Dec
11
2016

Cancer Rates Increased In Women

A recent review of cancer rates worldwide shows that cancer rates increased in women. This by itself is alarming, but based on that data the rates likely will go up by 60% in the year 2030. The main reason is the smoking discrepancy among women and men. Men as a group have been smoking more than women. But women as a group are more and more embracing smoking. All of the negative health consequences of the last 3 decades for men are just starting to show now for women as well.

The World Health Organization explains it this way: in high-income countries like Australia, Canada, the US and Western Europe women smoke at nearly the same rate as men.

But in low and middle income countries women do not smoke as much as men do. For instance in China 61% of men are smokers, but only 4.2% of women are smoking. In Argentina 34% of men are currently smokers, which compares to 23% of women who smoke in this country.

When this gap will close, likely by the year 2030 women will have a whole host of diverse cancers, heart attacks and strokes caused by the smoking habit.

Some statistics and facts

High-income countries like Australia, Brazil, Canada, Israel and many northern and western European countries have a 5-year survival rate for breast cancer of 85%. In contrast the 5-year survival rates are 60% or less in low- and middle-income countries like South Africa, Mongolia, Algeria and India.

Cancer prevention measures can make a big difference later in life. Examples are hepatitis B vaccination, which will prevent liver cancer; vaccinating boys and girls against HPV, which will prevent cervical cancer in women; also having regular mammograms will detect breast cancer earlier and improve breast cancer survival rates.

Dr. Nestor Esnaola, surgical oncologist at Fox Chase Cancer Center at Temple University Hospital, Philadelphia, PA said that the cancer prevention methods just mentioned might not be available in developing countries. Instead of mammographies repeat breast self-examinations are more important there. Campaigns against smoking can be utilized in order to prevent cancer of the lungs, the throat and neck. And if colonoscopies are not available, stool samples can be tested for blood and hemoglobin to check for colon cancer.

Different cancer rates increased in women in different countries

There are different cancer types that make the top chart for different countries. For instance in 2012 breast cancer was on top of most countries worldwide as the number 2 killer behind heart attacks and strokes. But other cancers ranked fairly high as well as causes of death: colorectal, lung and cervical cancers.

Despite this trend there were other countries like China and North Korea that had a higher incidence of lung cancer rather than breast cancer. The cancer researchers stated that the reason for this is that the smoking rates are higher in these countries. As already pointed out in China more than ½ of the men smoke, but only a small minority of the women smoke. But women in China are exposed to high amounts of secondhand smoke in addition to environmental pollution, which still causes a lot of lung cancer in women who live in this environment.

In many African countries cervical cancer is very common. Women, who are HIV positive, have a 5-times higher rate of cervical cancer. Southern and eastern Africa where there are higher rates of HIV, have higher rates of cervical cancer.

More data about women’s cancer rates

The American Cancer Society has produced a report entitled “Global Burden of Cancer in women, current status, trends, and interventions”, which points out some interesting statistics.

The greatest numbers of cancer cases and deaths occur among women in Eastern Asia. The estimate for 2012 worldwide was for 1.7 million cancer cases and 1 million deaths in women. China dominated its region with 75% of all female cancer cases and deaths in the region. In North America cancer cases and deaths within the US comprise 90% of the region. The cancer cases and deaths in India make up about 65% of the region of South-Central Asia.

The top mortality rates are found in low to medium income countries, namely in Zimbabwe, Malawi, Kenya, Mongolia and Papua New Guinea.

The most frequently diagnosed cancers in women are breast, lung, and colorectal cancers in economically more developed countries. However, the statistics are different for less developed countries where the top three most diagnosed cancers are breast, cervix, and lung. Similarly the leading causes of cancer deaths for women in developed countries are lung, breast, and colorectal cancers. In developing countries the leading causes of cancer deaths for women is cancer of the breast, lung, and cervix.

Cancer frequencies for women in different countries

The American Cancer Society reports that breast cancer is the most common diagnosed cancer among women in 140 countries. Cervical cancer is most common in 39 countries, all of which are low to medium income countries. There are some countries where other cancer types are more common. For instance in China and North Korea lung cancer is more common among women, in Mongolia and Laos liver cancer, and in South Korea it is thyroid cancer.

The most common cause of death from cancer in women is breast cancer in 103 countries, cancer of the cervix in 43 countries and lung cancer in 27 countries. Other most common cancer deaths in women are in the following countries:

  • Stomach cancer: in Bhutan, Peru, El Salvador, Guatemala, and Tajikistan
  • Liver cancer: in Laos, Mongolia and The Gambia
  • Colorectal cancer: in Japan and Slovakia
  • Esophagus cancer: in Turkmenistan.

Prevention and early detection

Changing the risk factors could modify 20% of breast cancer mortality worldwide. Avoiding excess body weight, physical inactivity and reducing alcohol consumption could all significantly reduce breast cancer mortality. For instance, women with a body mass index of greater than 35.0 have a 1.6-fold higher risk of breast cancer and a 2.1-fold higher mortality rate from breast cancer than women with a body mass index of less than 25.0.

Regular breast cancer screening with mammography is another tool that will reduce breast cancer mortality as the cancer is diagnosed earlier and treated at an early stage where it can often be cured. The WHO recommends for those countries where mammography programs are established that screening should be done only every two years and only between the ages of 50-69 to avoid X-ray over exposure.

Early detection, like for any cancer is the key for successfully treating breast cancer. When the cancer is found early, surgical removal in healthy tissue (lumpectomy) often cures breast cancer. Unfortunately in low to medium income countries the cancer is often found too late, requires more invasive mastectomies and radiotherapy and has a lower survival rate than in developed countries.

Cervical cancer

Cervical cancer accounts for the 4th most frequently diagnosed cancer in the world. In 2012 there were 527,600 cases diagnosed worldwide and 265,700 deaths from cervical cancer occurred in the same year. 90% of cervical cancers occur in developing countries with India accounting for 25% of the total cases. The key in detecting cervical cancer is a regular screening program. In developed countries where this has been in place cervical cancer incidence has decreased by 80% in 4 decades. At the other end of the spectrum are countries like Uganda, Zimbabwe, and some countries of Central and Eastern Europe where cervical cancer rates have been climbing. The reason for the spread is that the human papillomavirus (HPV) is now more common and screening methods for cervical cancer are not in place. HPV 16 and 18 are the most common carcinogenic subtypes of the human papilloma viruses; they are responsible for 70% of cervical cancers worldwide. By vaccinating teenagers before they engage in sex is a powerful tool to interrupt the infectious spread of an important risk factor for cervical cancer.

Instead of the traditional Pap test from the past the new test that is used now is an HPV-DNA test, a cervical swab that will detect DNA from HPV directly. It is more sensitive than the traditional Pap test. If the HPV-DNA test is positive, the patient is sent to a gynecologist who will perform a colposcopy test, which is a microscopic exam of the cervix. The gynecologist can use several effective treatment methods like a loop electrosurgical excision procedure, laser ablation therapy, cryotherapy or conization for deeper cervical cancer lesions.

As with any cancer early detection and treatment is paramount with cervical cancer. In developed countries the 5-year survival rate is 60 to 70%. In India the 5-year survival rate is 46%.

Cancer of the lung

In 2012 there were 583,100 cases of lung cancer in women worldwide and 491,200 died from it. Lung cancer is the second leading cause of cancer death in women and the third most common cancer. The statistics of lung cancer reflect the tobacco epidemic. It takes about 20 to 30 years after widespread smoking begins in a country before the deadly statistics set in. The peak of the cancer epidemic and the heart attack rates occurs about 30 to 40 years following the peak of smoking in that population.

Lung cancer rates in women have lagged behind men, because women as a group have started smoking later. In places like Hong Kong, the United Kingdom,

Australia, and the United States women started smoking earlier, and they are in the process of declining their smoking habit or quitting. This is reflected in the new lung cancer cases and also in the lung cancer mortality rates. Sadly, in many countries of Europe and Latin America women started smoking much later and they are still increasing their lung cancer statistics and mortality rates. Lung cancer killed 1.1 million men and 0.5 million women worldwide in 2012. In addition it is estimated that there are 21,400 lung cancer deaths annually from second-hand smoke in non-smokers worldwide.

Beside smoking there are other risks causing lung cancer. The estimated risk for women to die in millions is: exposure to household air pollution, 1.6; outdoor air pollution, 1.4; second-hand smoke, 0.35; occupational risk factors, 0.10; and residential radon, 0.03.

Cancer Rates Increased In Women

Cancer Rates Increased In Women

Conclusion

Women are still in the midst of a global increase of cigarette smoking, which starts often with female teenagers. As long as the smoking rate goes up there will be more breast cancer, lung cancer and cervical cancer. The American Cancer Society provided a detailed review of various cancers and how they are still increasing worldwide, because nobody pays attention to preventative measures. A simple step to prevent cancer is to quit smoking. Another step is to engage in regular physical activity. Finally keeping your body mass index under 25.0 is a third step that can be done by adopting a Mediterranean diet.

There are several pockets within the developed countries where cancer rates are coming down, which is encouraging. The initial overview and the three examples given here, breast cancer, cervical cancer and lung cancer were thought to illustrate this complex topic.

Nov
19
2016

New Breast Cancer Cure?

According to the popular press there is a new breast cancer cure. But we have to be careful with general statements like this. First of all, only 20% of breast cancers are HER2 positive. When the surgeon biopsies breast cancer, the sample is sent to the pathologist. Out of 100 samples, 20 come back with the finding that it is HER2 positive breast cancer.

Herceptin ® (trastuzumab), the first step of breast cancer cure

Trastuzumab is a monoclonal antibody that interferes with the HER2 receptor. Its main use is to treat HER2 positive breast cancers. But trastuzumab (brand name Herceptin ®) has serious side effects. In early HER2 positive breast cancer it can cause heart failure in 5.7–35.4% of patients, while it can cure breast cancer with a 35% cure rate of Her2-positive patients. It is significant to note that many of the studies used trastuzumab in combination with the chemotherapeutic agent anthracycline concomitantly. Anthracycline by itself has some cardio-toxic effect. Most of the studies that investigated heart toxicity of trastuzumab used this monoclonal antibody for 52 weeks. Newer studies show that as little as 9 weeks can be as effective in tumor cures, which reduces the risk of toxic effects on the heart to 2.2–2.3%.

Here is a link that shows visually what the effect of Herceptin ® may be on the HER2 surface marker in a woman with this type of breast cancer.

Lapatinib (Tykerb ® or Tyverb ®), the second step of breast cancer cure

Absorption of aging cancer cells, called apoptosis, is inhibited by overexpression of oncogenic receptor tyrosine kinases. These are proteins that normally function to remove dying cells at the end of their life span. In HER2 breast cancer these kinases are particularly common and are responsible for the cancer cell survival. Lapatinib is a dual tyrosine kinase inhibitor, which interrupts the HER2 and epidermal growth factor receptor (EGFR) pathways. Expressed in simpler terms, it removes dying cancer cells, so they cannot get reactivated or continue to survive.

A phase 3 clinical trial was done with Lapatinib and a chemotherapeutic agent, capecitabine (brand name Xeloda ®).  When the two drugs were combined there was a 51% reduction in the risk of the disease progression.

Herceptin ® and Lapatinib combined as new breast cancer cure

At the 10th European Breast Cancer Conference in Amsterdam professor Nigel Bundred reported about a trial involving 257 women with newly diagnosed, operable, HER2 positive disease. They were recruited between November 2010 and September 2015. Their biopsies were taken and the surgery was scheduled for 2 weeks later.

The trial was in two parts: The first 130 women were treated with trastuzumab (Herceptin ®) only, or lapatinib (Tyverb ®) only, for 11 days after diagnosis and before surgery. From other trials evidence became known that the combination of trastuzumab and lapatinib had better survival rates. The investigators decided to include a second part into their trial starting August 2013 with 127 women. Part of this trial was a combination treatment of trastuzumab and lapatinib.

Samples of tissue were taken from the original breast biopsies and then again two weeks later from the material of the breast surgery.

The pathologist examined the breast cells for a drop in the Ki67 protein, an indicator of cell proliferation. They also looked for an increase of apoptosis of 30% or more from the first date of the first biopsy. A “pathological complete response” was the term they used for a cure. When there was a partial cure, this was termed “minimal residual disease“. This meant that the tumor was less than 5 mm in diameter at the time of surgery. Women who had received the combination treatment had 11% pathological complete response (11% cure rate). 17% of the combination therapy group had minimal residual disease. There was no cure for those randomized to only trastuzumab and only 3% of that group had minimal residual disease.

New Breast Cancer Cure?

New Breast Cancer Cure?

Conclusion

Essentially this new research shows that two inhibitor drugs together are better than one or one in combination with conventional chemotherapy.

But we have to keep in mind that HER2 breast cancer includes only 20% of all types of breast cancer. When you hear that 11% of HER2 breast cancer was cured with the combination therapy in 11 days, it translates into only 2.2% of all types of breast cancer cured and only 3.4% of all breast cancer cases had minimal residual disease (tumor size less than 5 mm in diameter). This could be easily removed by surgery.

What everybody is excited about are the cures of 2.2% of all types of breast cancer (or 11% of HER2 breast cancer). This is a good start. But much more research needs to be done to increase this number of cures. While we are seeing some progress for one group of breast cancer patients, it is not nearly sufficient to advertise this treatment as a “cure”.

For all breast cancers a more promising option is available. A study from Wayne State University, Detroit, Michigan has shown that cryoablation therapy for breast cancer without excision can give a much higher cure rate of 100% over a period of 1 ½ years. In this procedure the tumor is left in place, but killed by cryotherapy (extreme local cold temperatures). It gives a cosmetically superior result. This is an accepted alternative, but is not yet widely practiced.