Author Archives: Dr Colin Holloway

Increased cardiac and stroke death risk in the first year after discontinuation of postmenopausal hormone therapy.

One of the benefits of oestrogen in the menopause is the big reduction in heart attack risk. Now we have evidence that going off your HRT too suddenly can increase your risk of a heart attack.
Menopause. 2018 Apr;25(4):375-379. doi: 10.1097/GME.0000000000001023.

Increased cardiac and stroke death risk in the first year after discontinuation of postmenopausal hormone therapy.

Author information

1
University of Helsinki and Helsinki University Hospital, Department of Obstetrics and Gynecology, Helsinki, Finland.
2
Folkhälsan Research Center, Biomedicum, Helsinki, Finland.
3
EPID Research Oy, Espoo, Finland.
4
National Institute for Health and Welfare, Helsinki, Finland.
5
Karolinska Institute, Department of Neurobiology, Care Sciences and Society, Division of Family Medicine, Stockholm, Sweden.

Abstract

OBJECTIVE:

The aim of the study was to evaluate the risk of cardiac and stroke deaths in women who discontinue postmenopausal hormone therapy (HT).

METHODS:

We analyzed the risk of death due to cardiac (n = 5,204) and cerebrovascular (n = 3,434) causes in Finnish women who discontinued systemic HT during 1994 to 2013 (n = 432,775). The risks were compared with those in the age-matched female background population and with those in age-matched HT users. Women diagnosed with cardiac or cerebrovascular events within 1 year before discontinuation of HT were excluded (n = 8,711).

RESULTS:

Women younger than 60 years at discontinuation of HT showed a significantly increased risk of cardiac death (after ≤5 y of HT exposure, standardized mortality ratio [SMR] 1.52, 95% CI 1.13-2.00; after >5 y of exposure, SMR 2.08, 95% CI 1.44-2.90) and stroke death (after ≤5 y of exposure, SMR 2.62, 95% CI 2.07-3.28; after >5 y of exposure, SMR 3.22, 95% CI 2.29-4.40) during the first year after treatment as compared with age-matched female background population. When compared with HT users, elevations in risks of cardiac and stroke deaths were even higher. Increased mortality risks were limited to the first post-HT year because increases in risks vanished or markedly decreased when the follow-up time was extended over more than 1 year.

CONCLUSIONS:

Discontinuation of postmenopausal HT may be associated with increased risk of cardiac and stroke death in the first posttreatment year. Further investigation is required to evaluate causality of the observed associations.

What are the risk factors for gynaecological cancers?

What are the risk factors for gynaecological cancers?

Risk factors are characteristics that increase the likelihood of developing a disease, such as a cancer. There are different types of risk factors; some can be modified (diet, physical activity) while others can’t (age, genetic factors). Sometimes, risk factors can be modified by some people but not others (e.g., the number of children).

Although certain factors can increase a woman’s risk for developing gynaecological cancer, they do not always cause the cancer. Many women carry at least one risk factor but still will not develop gynaecological cancer. Even if a woman with a gynaecological cancer carries a risk factor, it is difficult to know how much that risk factor contributed to the development of cancer.

Risk factors also look to explain cancer incidence of larger populations but sometimes it will be impossible to attribute “fault” to a risk factor. For example, cervical cancer is caused by Human Papilloma Virus (HPV), which is a sexually transmitted virus. However, the vast majority of women will have sexual intercourse at least once in their lives without developing cervical cancer. It remains unknown why some women develop cancer and others don’t.

pexels photo 1199590 exercise

While the causes of some gynaecological cancers are not fully understood some known risk factors include:

  • Increasing age. The risk of a woman being diagnosed with gynaecological cancer increases beyond the age of 65 years.
  • Family history or identified gene mutations. These mutations can include BRCA1, BRCA2 and Lynch Syndrome.
  • Reproductive history such as child-bearing. Women who have never given birth, who had infertility issues, never breastfed or had their first child after the age of 30 are at increased risk for ovarian cancer.
  • Exposure to hormones produced by the body or taken as medication. For e.g, estrogen-only hormone replacement therapy (HRT) taken as tablets after menopause may be associated with an increased risk of uterine cancer.
  • Previously diagnosed with cancer. A woman who has had any previous cancer diagnosis may have an increased risk of developing any type of cancer in the future. For example, women who developed breast cancer are at a significantly higher risk of developing uterine and ovarian cancer.
  • Exposure to diethylstilbestrol (DES) in the womb. DES is a synthetic form of the hormone estrogen. Doctors prescribed DES to help some pregnant women to prevent miscarriage between the 1940s and 1970s in Australia. Women whose mothers were given DES during pregnancy may be at increased risk of cervical and vaginal cancer.
  • Viral infection such as Human Papilloma Virus (HPV). Certain types of HPV have been linked to the development of cervical cancer.
  • The oral contraceptive pill. Long-term use of the oral contraceptive pill is associated with a small increased risk of cervical cancer. However, the pill has a substantial (50%) and long-lasting protective effect against ovarian and endometrial cancer.
  • Smoking. I discussed this in a previous blog ‘Does smoking cause gynaecological cancer?’ Smoking can increase your risk of ovarian, cervical and vulval cancer.
  • Being overweight. Increased caloric intake and obesity is strongly linked to an increased risk of endometrial cancer. Regarding ovarian cancer and cervical cancer, the evidence is less consistent.
  • Diet. A diet low in fruit, vegetables and grains, and high in saturated fat may increase ovarian cancer risk.

It is important for women to know their risk factors and talk about them with health professionals if concerned. Knowing cancer risk factors can prompt an individual to make lifestyle choices that may decrease cancer risk and improve overall health. Knowing risk factors could also aid in deciding if genetic testing may be an option.

Progesterone for the prevention and treatment of osteoporosis in women

Climacteric. 2018 Aug;21(4):366-374. doi: 10.1080/13697137.2018.1467400. Epub 2018 Jul 2.

Progesterone for the prevention and treatment of osteoporosis in women.

Abstract

Estradiol (E2) is women’s dominant ‘bone hormone’ since it is essential for development of adolescent peak bone mineral density (BMD) and physiological levels prevent the rapid (3-week) bone resorption that causes most adult BMD loss. However, deceasing E2 levels trigger bone resorption/loss. Progesterone (P4) is E2’s physiological partner, collaborating with E2 in every cell/tissue; its bone ‘job’ is to increase P4-receptor-mediated, slow (3-4 months) osteoblastic new bone formation. When menstrual cycles are normal length and normally ovulatory, E2 and P4 are balanced and BMD is stable. However, clinically normal cycles commonly have ovulatory disturbances (anovulation, short luteal phases) and low P4 levels; these are more frequent in teen and perimenopausal women and increased by everyday stressors: energy insufficiency, emotional/social/economic threats and illness. Meta-analysis shows that almost 1%/year spinal BMD loss occurs in those with greater than median (∼31%) of ovulatory disturbed cycles. Prevention of osteoporosis and fragility fractures requires the reversal of stressors, detection and treatment of teen-to-perimenopausal recurrent cycle/ovulatory disturbances with cyclic oral micronized progesterone. Low ‘Peak Perimenopausal BMD’ is likely the primary risk for fragility fractures in later life.

Progesterone plus estradiol or other antiresorptive therapies adds 0.68%/year and may be a highly effective osteoporosis treatment. Randomized controlled trials are still needed to confirm progesterone’s important role in women’s bone formation.

Science or Snake Oil: can turmeric really shrink tumours, reduce pain and kill bacteria?

Science or Snake Oil: can turmeric really shrink tumours, reduce pain and kill bacteria?

April 24, 2017 6.00am AEST

Disclosure statement

Gunveen Kaur does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond the academic appointment above.

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Victoria State Government provides funding as a strategic partner of The Conversation AU.

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Turmeric is a yellow coloured spice widely used in Indian and South East Asian cuisine. It’s prepared from the root of a plant called Curcuma longa and is also used as a natural pigment in the food industry.

In the literature, curcumin is reported to be an antioxidant that protects the body against damage from reactive molecules. These are generated in the body as a result of metabolism and cause cell damage (known as free radicals).

It’s also reported to have anti-inflammatory, anti-bacterial and anti-cancer properties, as well as encouraging the death of cells that are dangerous or no longer needed by the body.

Curcumin has been widely studied in relation to numerous ailments, but what does the literature say? Is consuming turmeric beneficial?

For aches and pains

Chronic inflammation has been linked to the development of numerous diseases such as obesity, diabetes, heart disease and cancer. There is some evidence curcumin reduces the levels of certain substances (cytokines) that produce inflammation.

Systematic reviews and meta-analyses, which combine data from several randomised controlled trials (where an intervention is tested against a placebo, while the subjects and those conducting the study don’t know who has received which treatment) support this finding to a certain extent.

A meta-analysis of nine randomised controlled trials showed taking curcumin supplements led to a significant reduction in cytokines that produce inflammation. But the authors claimed these reductions were modest, and it’s unclear if they would actually have a benefit in real life.

These trials were conducted with small sample sizes ranging from 10 to 50 people, which reduces the strength of the evidence. It’s difficult to draw a conclusion on a beneficial dose and how long you should take curcumin, or the population group that can benefit the most from curcumin.

A meta-analysis investigated the effects of turmeric/curcumin on pain levels in joint arthritis patients. The group supplemented with 1000mg of curcumin per day said they had reduced pain compared with the placebo group.

In this study, curcumin was found to be as effective as ibuprofen in terms of reducing pain levels in these patients. But the authors of this meta-analysis themselves suggested that due to small sample size and other methodological issues there is not sufficient evidence to draw definitive conclusions.

Turmeric is often marketed as an anti-inflammatory. Screen shot/Suppkings

For diabetes and heart disease

Curcumin is also thought to be beneficial in preventing insulin resistance (which leads to increased blood sugar), improving high blood sugar and reducing the toxic effects of high blood glucose levels.

But these studies have been conducted in animals and are very few human trials have been conducted in this area.

One study that reported reduction in blood glucose levels in type 2 diabetes patients reports a change in blood glucose from 8.58 to 7.28 millimoles per litre after curcumin supplementation. People with levels above seven are classified as diabetics. So in clinical terms, the change is not that much.

Similarly in relation to heart disease, animal studies show benefits of curcumin supplementation in improving heart health, but there are very few clinical trials conducted in heart disease patients.

Smaller clinical trials looking at ten patients also show benefits of curcumin in reducing serum cholesterol, which is a risk factor for heart disease. But meta-analysis looking at combined effects of different trials does not show these benefits.

For cancer

Curcumin has also been widely studied in relation to its anti-cancer properties. Laboratory and animal studies support this claim, but the evidence for cancer prevention in human trials is lacking.

Although there are some small studies (in 25 cancer patients) that showed reductions in precancerous lesions, and two patients showed shrunken tumors, this small number is not enough to conclude anti-cancerous effects of curcumin.

There is some evidence curcumin lessens the severity of side-effects from radiation therapy such as radiation-induced dermatitis and pneumonitis (inflammation of lungs), but not the cancer itself.

Safety

Research shows not all curcumin we take orally is absorbed. This has led to the use of other things such as lipids (fats) and piperine (found in black pepper), to help it absorb into our system.

High intakes (up to 12 grams a day) of curcumin can cause diarrhoea, skin rash, headaches and yellow-coloured faeces. Looking at the Indian population, they consume about 100mg of curcumin a day, which corresponds to 2 to 2.5 grams of turmeric per day.

Consuming turmeric as part of a balanced diet is probably good for you. Injecting it definitely isn’t. from http://www.shutterstock.com

But they also consume these amounts over relatively long periods of time (typically their lifespan). There are reports of lower cancer rates in the Indian population and this has been linked to turmeric consumption, but there are no longer term trials proving this link.

It appears that in order to receive benefits from high doses over a short period of time, people are now resorting to injecting turmeric intravenously. There is no evidence to support the benefits of high doses of turmeric or IV injections of turmeric at all.

In fact, at very high doses, curcumin’s predominant activity switches from antioxidant to pro-oxidant, which means rather than preventing cells from damage, it promotes cell damage and has also been reported to cause tumours in rodents.

Although curcumin is showing some encouraging effects in reducing markers of inflammation in humans, the majority of the pharmacological effects of curcumin are in lab studies or animal experiments. Until there are more high quality randomised controlled trials conducted to confirm the benefits of curcumin or turmeric, it’s best to consume turmeric orally as a spice as part of a healthy, nutritious diet.

Another major study about the safety of HRT.

This is a study using synthetic HRT over a number of years, showing even this form of hormone treatment did not increase the amount of cancer or heart disease in women.
JAMA. 2017 Sep 12;318(10):927-938. doi: 10.1001/jama.2017.11217.

Menopausal Hormone Therapy and Long-term All-Cause and Cause-Specific Mortality: The Women’s Health Initiative Randomized Trials.

Author information

1
Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts.
2
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
3
National Heart, Lung, and Blood Institute, Bethesda, Maryland.
4
Department of Family Medicine and Public Health, University of California, San Diego, School of Medicine, San Diego.
5
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance.
6
now with City of Hope National Medical Center, Department of Medical Oncology and Therapeutics Research, Duarte, California.
7
MedStar Health Research Institute, Washington DC.
8
Georgetown/Howard Universities Center for Clinical and Translational Sciences, Washington DC.
9
Department of Health Promotion Sciences, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson.
10
HealthPartners Institute for Education and Research, Minneapolis, Minnesota.
11
Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham.
12
Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, California.
13
Department of Medicine, The Ohio State University, Columbus.
14
Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis.
15
Cardiology Division, George Washington University School of Medicine and Health Sciences, Washington DC.
16
Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, North Carolina.
17
Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina.
18
Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, New York.

Abstract

Importance:

Health outcomes from the Women’s Health Initiative Estrogen Plus Progestin and Estrogen-Alone Trials have been reported, but previous publications have generally not focused on all-cause and cause-specific mortality.

Objective:

To examine total and cause-specific cumulative mortality, including during the intervention and extended postintervention follow-up, of the 2 Women’s Health Initiative hormone therapy trials.

Design, Setting, and Participants:

Observational follow-up of US multiethnic postmenopausal women aged 50 to 79 years enrolled in 2 randomized clinical trials between 1993 and 1998 and followed up through December 31, 2014.

Interventions:

Conjugated equine estrogens (CEE, 0.625 mg/d) plus medroxyprogesterone acetate (MPA, 2.5 mg/d) (n = 8506) vs placebo (n = 8102) for 5.6 years (median) or CEE alone (n = 5310) vs placebo (n = 5429) for 7.2 years (median).

Main Outcomes and Measures:

All-cause mortality (primary outcome) and cause-specific mortality (cardiovascular disease mortality, cancer mortality, and other major causes of mortality) in the 2 trials pooled and in each trial individually, with prespecified analyses by 10-year age group based on age at time of randomization.

Results:

Among 27 347 women who were randomized (baseline mean [SD] age, 63.4 [7.2] years; 80.6% white), mortality follow-up was available for more than 98%. During the cumulative 18-year follow-up, 7489 deaths occurred (1088 deaths during the intervention phase and 6401 deaths during postintervention follow-up). All-cause mortality was 27.1% in the hormone therapy group vs 27.6% in the placebo group (hazard ratio [HR], 0.99 [95% CI, 0.94-1.03]) in the overall pooled cohort; with CEE plus MPA, the HR was 1.02 (95% CI, 0.96-1.08); and with CEE alone, the HR was 0.94 (95% CI, 0.88-1.01). In the pooled cohort for cardiovascular mortality, the HR was 1.00 (95% CI, 0.92-1.08 [8.9 % with hormone therapy vs 9.0% with placebo]); for total cancer mortality, the HR was 1.03 (95% CI, 0.95-1.12 [8.2 % with hormone therapy vs 8.0% with placebo]); and for other causes, the HR was 0.95 (95% CI, 0.88-1.02 [10.0% with hormone therapy vs 10.7% with placebo]), and results did not differ significantly between trials. When examined by 10-year age groups comparing younger women (aged 50-59 years) to older women (aged 70-79 years) in the pooled cohort, the ratio of nominal HRs for all-cause mortality was 0.61 (95% CI, 0.43-0.87) during the intervention phase and the ratio was 0.87 (95% CI, 0.76-1.00) during cumulative 18-year follow-up, without significant heterogeneity between trials.

Conclusions and Relevance:

Among postmenopausal women, hormone therapy with CEE plus MPA for a median of 5.6 years or with CEE alone for a median of 7.2 years was not associated with risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow-up of 18 years.

Trial Registration:

clinicaltrials.gov Identifier: NCT00000611.

What should I eat to improve my skin?

Health Check: what should I eat to improve my skin?

“Get radiant skin!” “Banish your pimples!” “Glow from the inside out!”

These are some statements that pop up when asking Google the age-old question: what should I eat to improve my skin?

Recommendations usually include cutting out chocolate, other junk foods and dairy products. But is there evidence to actually support this?

Chocolate

Researchers started exploring the link between diet and skin health, particularly acne, in the mid-1900s. Dermatology textbooks from the 1930s advised restricting carbohydrates, sweets and junk foods to improve acne. But these recommendations were based on doctors’ experiences and observations, not quality research.

Chocolate is one junk food that often gets blamed as an aggravating factor of acne. In a 1969 study, 65 people with acne were asked to eat one chocolate bar per day for four weeks. They were either given a bar that contained ten times the amount of chocolate found in a typical bar, or a bar that looked identical but contained no chocolate.

Results showed participants who ate the chocolate bars did not have more breakouts than those who didn’t eat the chocolate.

Studies on whether chocolate has an effect on your skin are so far inconclusive. Charisse Kenion/Unsplash

Similar results were found in a 1971 study. Twenty-seven students who reported being sensitive to dietary acne triggers ate large amounts of chocolate, milk, roasted peanuts or soft drinks for one week. No significant difference in the number of breakouts was observed between the groups.

But these studies also had some major limitations. The 1969 study was sponsored by the Chocolate Manufacturers Association of the United States of America. And both studies did not assess participants’ intake of other foods during the study period, which may have influenced their complexion.


Read more: Research Check: does eating chocolate improve your brain function?


More recently, a 2011 study including ten men aged between 18-35 found significant changes occurred in the severity of acne after a single intake of pure chocolate (100% cocoa). There was a strong association between the amount of chocolate consumed and the number of breakouts four and seven days after they ate the chocolate.

So overall, study findings show conflicting results, and clear recommendations about chocolate cannot yet be made.

But better-quality research does suggest other dietary strategies worth trying if you want to improve your skin. These include eating more fruits and vegetables as well as foods with a lower glycaemic load.

Glycaemic load

The glycaemic index (GI) is a ranking between 0-100 given to carbohydrate-containing foods to describe how quickly the carbohydrates are digested into glucose (sugar) and absorbed into our blood. The lower the GI, the slower the rise in blood glucose levels when the food is consumed. Most junk foods (candy, chips and cakes) have a high GI.


Read more: GI diets don’t work – gut bacteria and dark chocolate are a better bet for losing weight


Glycaemic load (GL) builds on the concept of GI but also considers the amount of food being eaten. This provides a more accurate picture of the overall effect the food has on blood glucose levels.

Once the glucose enters the blood, a hormone called insulin moves it into our cells to be used for energy. Diets with a high GL trigger a higher response in insulin. This high level of insulin increases a hormone called the insulin-like growth factor (IGF), which has been associated with skin breakouts – like pimples.

Junk foods have a high glycaemic index. from shutterstock.com

In a 2008 randomised control trial (considered the gold standard in scientific research as it compares findings between two groups), 31 males with acne, aged 15-25, were asked to follow either a low-GL or a high-GL diet for 12 weeks. The low-GL group was instructed to substitute high-GI foods (processed cereals, potatoes and white bread and rice) with lower-GI foods (lean meats, fruits and wholegrain bread and pasta).

The high-GL group was encouraged to include carbohydrates as a regular part of their diet and wasn’t educated about GI. Those following the low-GL diet saw their acne improve and lost more weight.

A 2007 randomised controlled trial had similar findings. But because participants in both studies who were following the low-GL diet lost weight, it’s also possible improvements in their skin were due to weight loss and not the diet itself.

Fruit and vegetables

Fruits and vegetables are wonderful for our bodies in many ways, but research shows they can also give our skin a natural, healthy glow – by tinting it yellow and red.

Our skin colour is influenced by three pigments – haemoglobin, carotenoids and melanin. Many fruits and vegetables contain carotenoids. These are responsible for the deep green colour of broccoli and spinach, the vibrant orange colour of carrots and oranges, and the red hue of capsicums and tomatoes.

Eating lots of oranges could give your skin a healthy, golden glow. freestocks.org/Unsplash

When you eat fruits and vegetables, these pigments can accumulate in your skin, leading to a healthy golden glow. The same benefits haven’t been seen with supplements, so it’s best to get your carotenoid hit from eating lots of different fruits and vegetables.


Read more: Food as medicine: why do we need to eat so many vegetables and what does a serve actually look like?


What about milk?

Milk naturally contains anabolic steroids, growth hormones and other growth factors. In a complicated metabolic pathway, these factors lead to a higher release of insulin and insulin-like growth factor, which can stimulate the development and progression of acne.

A number of studies have examined the alleged connection between milk and acne. In 2005, 50,000 women recalled their high school diet and were asked if they had ever been diagnosed with severe acne by their doctor.

Researchers found those who had a higher reported intake of milk (particularly skim milk) more commonly suffered from acne. A 2006 study with around 6,000 teenage girls and a 2008 study with around 4,700 teenage boys showed similar results.

Milk has been associated with acne development. from shutterstock.com

But no randomised controlled trials have been conducted that examine the association between milk and acne. This means whether dairy is a cause of acne hasn’t yet been established. High-quality research is needed before specific recommendations can be made.

If you are trying to improve your skin’s complexion, you could try these strategies:

  • reduce high-GL foods by decreasing the amount of processed, junk food you eat
  • add low-GL foods that won’t spike your blood glucose levels (vegetables, sweet potatoes, barley, beans and multigrain bread)
  • eat a diverse range of fruits and vegetables to get a healthy glow.

The New Biology of Estrogen-induced Apoptosis Applied to Treat and Prevent Breast Cancer

Many of you will be surprised that oestrogen can be used to treat breast cancer. Nothing is ever straight forward in medicine, and the oestrogen/breast cancer connection is one of those.

Published in final edited form as:
Endocr Relat Cancer. 2015 February ; 22(1): R1–31. doi:10.1530/ERC-14-0448.

The New Biology of Estrogen-induced Apoptosis Applied to Treat and Prevent Breast Cancer
V Craig Jordan
Departments of Breast Medical Oncology and Molecular and Cellular Oncology, MD Anderson Cancer Center, Houston, Texas
Abstract
The successful use of high dose synthetic estrogens to treat post-menopausal metastatic breast cancer, is the first effective “chemical therapy” proven in clinical trial to treat any cancer. This review documents the clinical use of estrogen for breast cancer treatment or estrogen replacement therapy (ERT) for postmenopausal hysterectomized women which can either result in breast cancer cell growth or breast cancer regression. This has remained a paradox since the 1950s until the discovery of the new biology of estrogen induced apoptosis at the end of the 20th century. The key to triggering apoptosis with estrogen is the selection of breast cancer cell populations that are resistant to long term estrogen deprivation. However, through trial and error estrogen independent growth occurs. At the cellular level, estrogen induced apoptosis is dependent upon the presence of the estrogen receptor (ER) which can be blocked by non-steroidal or steroidal anti-estrogens. The shape of an estrogenic ligand programs the conformation of the ER complex which in turn can modulate estrogen induced apoptosis: class I planar estrogens (eg: estradiol) trigger apoptosis after 24 hours whereas class II angular estrogens (eg: bisphenol triphenylethylene) delay the process until after 72 hours. This contrasts with paclitaxel that causes G2 blockade with immediate apoptosis. The process is complete within 24 hours. Estrogen induced apoptosis is modulated by glucocorticoids and cSrc inhibitors but the target mechanism for estrogen action is genomic and not through a non-genomic pathway. The process is step wise through the creation of endoplasmic reticulum stress and, inflammatory responses that then initiate an unfolded protein response. This in turn initiates apoptosis through the intrinsic pathway (mitochondrial) with subsequent recruitment of the extrinsic pathway (death receptor) to complete the process. The symmetry of the clinical and laboratory studies now permits the creation of rules for the future clinical application of ERT or phytoestrogen supplements: a five year gap is necessary after menopause to permit the selection of estrogen deprived breast cancer cell populations to become vulnerable to apoptotic cell death. Earlier treatment with estrogen around the menopause encourages ER positive tumor cell growth, as the cells are still dependent on estrogen to maintain replication within the expanding population. An awareness of the evidence that the molecular events associated with estrogen induced apoptosis can be orchestrated in the laboratory in estrogen deprived breast cancers, now support the clinical findings for the treatment of metastatic breast cancer following estrogen deprivation, decreases in mortality following long term antihormonal adjuvant therapy, and the results of ERT and ERT plus progestin in the Women’s Health Initiative for women over the age of 60. Principles have emerged to understand and apply physiologic estrogen therapy appropriately by targeting the correct patient populations.

What do the different stages of cancer mean? » Professor Andreas Obermair

What do the different stages of cancer mean?

As a gynaecological oncologist, I see patients with gynaecological cancers including ovarian, cervical, endometrial (uterine), vulval and vaginal cancer.

If you are diagnosed with cancer, you will normally be given a cancer ‘stage’. The stage of a cancer describes how far it has grown and spread in the body at the time of diagnoses. To determine the stage this will involve having scans, biopsies and possibly further tests. The stage of the cancer will help us work out the most efficient and least harmful treatment options for patients.

microscope

All cancers are staged at the time of diagnosis. Stage is used to describe the spread of cancerous growths, like gynaecological, breast, bowel or lung cancers. Blood cancers are staged in different ways.

Typically, a numbered staging system is used. Most types of cancer have 4 stages, numbered from 1 to 4. You may also see roman numerals used.

Stage 0 cancer (in-situ)

Stage 0 or ‘carcinoma in situ’ means that there is a group of abnormal cells in one area of the body but these cells do not constitute cancer yet. Untreated, these cells could progress into cancer. In situ means ‘in place’. These pre-cancerous cells are still in the same place where they started and have not spread. Prognosis of cancer at this stage is highly curable, and typically involves surgery to remove the cells or tumour.

Stage 1 cancer

The cells now have features consistent with cancer but the cancer is still small and contained in the organ it originally developed in. It has not spread to any lymph nodes, organs, or body areas. This is often called early stage cancer. Based on additional risk factors, some patients might still need further treatment to reduce the risk of a cancer recurrence.

Stage 2 and 3 cancer

Stage 2 or 3 cancer means that the cancer is larger or has spread into nearby tissues or lymph nodes (metastases). Many of stage 2 and 3 cancers are still curable, depending on the location of the metastases, the cell type and whether the cancer responds to chemotherapy, radiation treatment or hormone intervention.

Stage 4 cancer

Stage 4 cancer means that the cancer has spread to other areas of the body. The treatment of stage 4 gynaecological cancer may be curative (aiming for cure) or palliative (aiming for symptom control).

For example, ovarian cancer is staged by FIGO (International Federation of Gynecology and Obstetrics) as follows:

Stage 1 – the cancer is in 1 or both ovaries and has not spread to other organs or tissues.

Stage 2 – the cancer is in 1 or both ovaries and has spread to other organs in the pelvis, such as the uterus, fallopian tubes, bladder or colon.

Stage 3 – the cancer is in 1 or both ovaries and has spread outside the pelvis to other parts of the abdomen or nearby lymph nodes.

Stage 4 – the cancer has spread to other parts of the body beyond the pelvis and abdomen, such as the lungs or liver.

Some cancer require surgery to determine a stage (uterine, ovarian and vulval cancer) whereas other cancers (cervical and vaginal cancer) do not require surgery to obtain staging information.

This means that sometimes staging information is not readily available initially; histopathology reports may take a few days and provide important information in ovarian, uterine and vulval cancer.

In a specialised gynaecological oncology practice, surgeons tend to use the FIGO staging system.

Sometimes, the TNM staging system may also be used to determine cancer spread:

T (Tumour) indicates the depth of the tumour invasion – the higher the number (between 1 and 4), the further the cancer has spread.

N (Nodes) indicates whether the lymph nodes are affected – a number between 0 and 3 describes how much the cancer has spread to lymph nodes near the bladder.

M (Metastasis) indicates whether the cancer has spread to other parts of the body – M1 means the cancer has spread to other organs or lymph nodes that are not near the bladder; M0 means there is no sign of the cancer spreading to other parts of the body.

Cancer can also be referred to as ‘localized’ where the cancer is limited to the place it originated (no spread), ‘regional’ where the cancer has spread to lymph nodes, tissues, or organs, and ‘distant’ where the cancer has spread throughout the body.

Our patients are 100% entitled to know what their cancer stage is. In our practice, we are very forthcoming with information about our patients’ cancer stage (once it is known) and other relevant factors.

If you wish to receive regular information, tips, resources, reassurance and inspiration for up-to-date care, that is safe and sound and in line with latest research please subscribe to receive my blog, or like Dr Andreas Obermair on Facebook. Should you find this article interesting, please feel free to share it. 

Integrative Cancer Care – Extremely Helpful Tips from Leading Expert Oncologist Dwight McKee

This is one of the more important post I have done. It is long, but full of good advice for anyone with cancer or a loved one/friend with cancer. I have a number of patients who will benefit from this, so read very carefully.

Integrative Cancer Care – Extremely Helpful Tips from Leading Expert Oncologist Dwight McKee

This was a fantastic call with oncologist Dwight McKee who really showcased his mastery of this subject by providing a handful of simple yet profound tips regarding integrative cancer care.

Episode Intro

Dr. Michael Ruscio, DC: Hey, everyone! Welcome to Dr. Ruscio Radio. This is Dr. Ruscio. Today I am here with Dr. Dwight McKee. And we are going to be undergoing part 2 of our series on cancer therapy. And we are very excited to have this conversation. Dwight, welcome to the show.

Dr. Dwight McKee: Thanks so much for having me.

[Continue reading below]

Dr. R’s Fast Facts Summary

Reduce anxiety from the cancer diagnosis

  • Consider taking beta-blockers to reduce stress associated with diagnosis
  • Inderal 40mg 2x/day, followed by tapper once less stressed

Checkpoint Inhibitors

  • 10-20% response range
  • Opdivo and Keytruda
  • Can be very expensive –  $400,000 for a yr of treatment
    • Insurance covers if it is considered a first line therapy for your cancer type

Best way to learn about Integrative Cancer Care

  • Avoid the internet – there are over a million articles it can be too overwhelming
  • Speak with an experienced practitioner to start (a practitioner in their mid-40s would likely be more open to integrative therapies)
  • Trust your gut on who you are seeing, confidence in your practitioner is vitally important
    • Get 2nd and 3rd opinions
    • CONFIDENCE CURES CANCER (fear does the opposite)

Immunotherapy or Chemotherapy?

  • If you have a curable cancer – proceed with standard therapies
    • Unless you “categorically refuse chemotherapy” then you may qualify for immunotherapy if it is approved for your type and stage of cancer
  • If you have stage 4 cancer or have relapsed, find out from your oncologist if there is an approved immunotherapy for your type and stage of cancer
  • About 3% of metastatic cancers are curable with chemotherapy
    • About 12% of metastatic cancers are curable with some combination of chemotherapy and radiation
      • Lymphomas, Leukemias, Testicular Cancer

Natural Therapies and Support

  • Curcumin or Turmeric
  • Herbs that help support a healthy inflammatory response
    • Ginger
    • Vitamin C and IV Vitamin C (work for some cancer patients though we do not know which patients)
  • Post chemotherapy, consider mitochondrial support to prevent loss of energy

When treating with curative intent

  • A minimalist approach is favorable
    • Focus on good diet, exercise, stress management, body/mind therapies (acupuncture)
    • Careful with supplements
    • Use mitochondrial therapy post-cancer treatment or between treatments depending on your providers’ recommendations

Diet

  • Ketogenic diet can help certain types of cancer, especially early on, recently diagnosed cancer that hasn’t been treated. Then shift out of it. (good for anabolic cancers NOT good for catabolic cancers)
  • If cancer is leading to weight loss and/or edema use a plant based diet (for catabolic cancers)
  • Fasting dramatically reduces toxicity
    • Not recommended for people dramatically underweight who are not able to regain weight by the next cycle
Dr Ruscio Dwight McKee Podcast
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In this episode…
Episode Intro … 00:39
Dr. McKee’s Background… 01:00
How to Learn About Immunotherapy … 10:00
Immunotherapy … 16:00
Curable Cancers … 21:00
Natural Therapies … 31:35
Treatment … 34:45
Curative Intent Treatment … 37:51
Diet … 40:00
Beta-blockers … 48:20
Episode Wrap-up … 41:24

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DrMR: Can you tell people a little bit about your background, in case they have never come across your name before?

DrDM: Sure. I have an unusual career path. I started out doing an M.D./Ph.D. program at Case Western Reserve because I had gotten interested in research when I was in college at Williams College in biochemistry. So I thought I wanted to do research. And I did the M.D./Ph.D. in Pharmacology at Case Western Reserve. It was supposed to be a 6-year program, but when I was into it, it was clear that it was really a 9 or 10-year program.

And I grew up in Cleveland. And I think I had seasonal affective disorder as well. So it was kind of closing in on me. And I got very interested in clinical medicine after I was exposed to it. You know, you never know what you will like until you experience it. And so I ended up doing a year of research. And when I had taken all the graduate courses, I just finished my M.D.

I did an internship, and during that time I discovered and got really interested in nutritional medicine and alternative cancer therapies. And I went into practice. I joined Integral Health Services, which had been started by Sam McClanahan. We had two M.D.s, two chiropractors, two massage therapists, two nutritionists, two psycho-therapists, and an acupuncturist. So we were one of the first holistic health centers in the country, certainly among the first on the East coast. This was 1976.

And I started having all kinds of cancer patients coming. Then I started really studying all the extant alternative cancer therapies of the time. I started experimenting with them and using them. These were people who either didn’t want conventional therapy or had been told there was nothing more that could be done. And I was able to help a significant percentage of these people, probably 20%.

And ultimately I got frustrated with what I could accomplish. And I was also frustrated by the attitude of oncologists at the time because I would have stage IV patients who were getting better. They felt better. They were eating, and they were gaining weight. Their pain was decreasing. Functionally, they were improved on every level.

And they would go for their oncology visit and the oncologist would just stick a pin in their balloon. And they would say, well, you know, that’s all fine and good. But you have an incurable disease, and you’re going to be dead in six months. And I saw how devastating that nocebo effect, the opposite of a placebo effect, was. And I decided I needed to be an oncologist.

Dr. McKee’s Background

So at the age of 40, after 12 years in practice, I went back into training. I had to do a second internship because my first one wasn’t in internal medicine. I had to do an internal medicine internship, and then two years of internal medicine residency, and then a three-year hematology/oncology fellowship, which I finished in 1995.

And then I practiced integrative oncology, which didn’t really exist. But I started practicing it in San Diego and then continued in Montana until 2001. And then I moved back to California. And I shifted to doing integrative cancer consultations for other physicians who were by that time doing the non-oncology side of integrative cancer therapy, which had now become a thing.

So I was educating them about how oncology works and what the oncologists are thinking and helped them to communicate with oncologists in a non-threatening way, always thinking of the benefit of their patients. And I emphasized if patients are caught in a cross-fire between their integrative doctor and their oncologist, it’s stressful to the patient and that’s bad for the patient, no matter what the therapy is.

So I spent about 15 years doing that. And I also work as the scientific director of a nutraceutical company that was started by ex-patients and old friends of mine in Arkansas, which ended up becoming quite popular in Europe. So I’m spending a lot of time flying to Europe and back, working with people over there in that project. And I continue to have time to read and stay on the front lines.

When I got into oncology in 1992, what I was really interested in was the sort of high tech immunology, immunotherapy. And I was able to do two years of tumor immunology research at this research institute, which was really interesting. But it was not quite prime time yet. And it is now. And I am so excited to see it.

immune systemAnd I can see how much potential there is to integrate these new immunotherapies with nutrition and exercise and body/mind techniques and many integrative techniques because now we are talking about getting the immune system to work better. That didn’t work. There was a lot of naiveté in the alternative cancer community about, oh, if we stimulate the immune system and we give all these medicinal mushrooms and use this and that, it’s going to work.

But nobody understood until quite recently the ways that tumors vary and sophisticatedly block the immune response. And now we have ways with monoclonal antibodies to dissect this complex interaction in ways that tumors have devised to shut off the immune response, interfere with the tumor’s ability to shut that off, and then allow the immune response to go forward.

These are called check-point inhibitors. And they get responses in the kind of 10-20% range. So it’s not where it needs to be. But the responses are much more durable than those achieved by chemotherapy. And I have a colleague in Vienna who has integrated check-point inhibitors with hyperthermia and fever range interleukin-2 and several other things. And he is getting 60% response rates and 20% complete response rates.

So I know that’s possible. And I think that we are going to get better and better and better at curing cancer, which is a good thing because we are on the threshold of an epidemic of cancer because of what we have done to our food supply and our planet and our lifestyles.

DrMR: There are so many ways that I want to go from there. And there are so many great things that you said. And I just want to commend your staying power to undergo that long rigorous academic road that you went through. And thank you for that.

DrDM: Yea, it was a bit grueling.

DrMR: I’m sure.

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DrMR: So these inhibitors that you are mentioning, are these something that are available in the U. S.?

DrDM: Yea, this is standard therapy. These are drugs like Opdivo and Keytruda. And they are very expensive. A year’s therapy can easily run $200,000 to $300,000 to $400,000.

DrMR: Wow! So insurance coverage, I am assuming, for these is nearly impossible to come by?

DrDM: No, insurance does cover the ones where they are indicated, where there is an FDA indication. And like every couple of months, there is a new FDA indication. I believe Opdivo is now indicated first line in metastatic non-small-cell lung cancer.

How To Learn About Immunotherapy

DrMR: That’s great to hear. So where do you start someone? Let’s say our audience is a mixture of both practitioners and the lay audience. Where would you start someone who says, “Okay, I’ve done some reading and I feel overwhelmed by the topic?”

I don’t even get close to providing people with a list of recommendations for specific cancers, because there are many types of cancers and there are many types of recommendations. But where would you start someone? Is there an association they should go to? Or should they plug in somewhere in particular for the right type of information from an educational standpoint?

DrDM: Well, one thing I would discourage is just random web surfing, because those are dangerous waters. There are over a million websites that are thinly disguised advertising for one product or another. And there are more products that have helped someone with some kind of cancer some time than anybody even with unlimited funds could possibly swallow, ingest, inject. So, I would encourage people to find somebody experienced in the field as a guide.

After Cancer Care Book CoverI wrote a book with an oncologist friend of mine, who is the head of integrative oncology for the New Jersey satellite of M.D. Anderson Cancer Center, and my old friend Gerald Lemole, who was one of the first integrative cardiothoracic surgeons, who happens to be Dr. Oz’s father-in-law. Dr. Oz wrote the foreword to our book. It is called After Cancer Care.

And we wrote it as after cancer care, so as not to have the conflict that arises when people want to take supplements and particularly supplements during treatment. Because there is little data about that, oncologists don’t know about it. And so they are worried about it that it would interfere. When I was treating patients, I would use all sorts of things along with treatment, and I got very good results. But it hasn’t been studied.

DrMR: So is it fair to say that the natural therapies have viability for perhaps mitigating some symptoms, but not treating the cancer during cancer therapy? And then mainly the cancer therapies are more preventing recurrence? Is that where you say they are the strongest?

DrDM: Well, you know, that’s really hard to say. I think there is a role for them both. The majority of patients take supplements during therapy and they just don’t tell their oncologist, which is a suboptimal situation. But the reason they don’t is that they are afraid that if they tell them that they are taking things that they will them to stop.

What I often did was I would put together smoothie recipes for people with various tinctures and herbal concentrates and so forth. And just the concept of them saying I had a smoothie in the morning with a bunch of stuff in it, that doesn’t hit the alarm bells for most oncologists like well I take this supplement of that. I’m taking green tea extract or whatever.

And I think the tides are slowly beginning to shift. And I think there is more openness, especially among younger oncologists. I think the optimal kind of age for people who are interested in integrative cancer therapy for choosing an oncologist is somebody in their mid-40s. They are old enough to be experienced, but young enough not to be a victim of psycho-sclerosis as I call it, which is a hardening of the attitudes.

And I think it is also a very, very personalized journey. And what I encourage patients to do is trust their intuition, because this is way more complex than we have the science to inform. And if people will really trust their instincts, I have seen that work so many times about which doctor to use, about which herbalist to work with, which nutritionist, which psycho-therapist, and even what things to take on what day.

If people tune in to their inner guidance, and obviously some people are better at that than others. People who tend to be very in their heads have a harder time with that than people who have a lot of meditation experience and experience with connecting to their inner self.

And I think it’s a mistake for people to copy what someone else has done that has been successful. I think there are general principles that apply across the board. But the specifics can vary quite a lot.

There are more and more professionals in this space. And I encourage people to get in touch with one that they have confidence in. Get an oncologist that they have confidence in, a surgeon that they have confidence in, because it is confidence that cures cancer.

Immunotherapy

DrMR: And are there any important…And I guess maybe we can organize these into conventional medicine and then alternative medicine but are there are new and novel breakthroughs of late that are important for people to be aware of? And maybe perhaps there could be even questions one could use as indicators of, okay if this oncologist or herbalist hasn’t heard of X, Y, or Z, then perhaps they are not as up to snuff on the literature as they should be.

DrDM: Well, the first advice that I would give is that if somebody has a cancer that’s highly curable with standard therapy, do that. I have seen too many people who had a curable cancer who went off into some pretty arcane things because they were afraid of having chemotherapy or radiation or both and ended up dying of what was a curable cancer.

DrMR: Right.

DrDM: Find out. If you have an early stage Hodgkin’s disease, by all means, have conventional therapy. If you have early head and neck cancer, by all means, have conventional therapy. If you relapse, then it’s time to go looking. Or if you are diagnosed with a stage IV cancer and there is not a curative therapy, then start looking right away.

But the first question I would ask the oncologist is this. Is there an immunotherapy that is approved for my type and stage of cancer? Immunotherapy tends to be used at the end of the line because that’s the way our clinical trial system works. People go into clinical trials when they have failed all the standard therapies; or better, all the standard therapies have failed them. Then they get into clinical trials.

And immunotherapies are going to work best when the immune system is intact. And all of the conventional therapies, surgery, radiation, chemotherapy, they all take a toll on the immune system. So immunotherapy is going to work best up front. And they are going to work best in a healthy person. It’s possible to have cancer and be healthy.

One of my colleagues who is a brilliant herbalist–I teach seminars with him a couple of times a year–is up in Oregon. This was in the early days when immunotherapy was all still in clinical trials, referred to as the checkpoint inhibitors. They inhibit checkpoints that are built into the immune system to avoid autoimmune disease.

And cancer exploits those checkpoints. So blocking those checkpoints with a specific antibody can allow the immune system to get past that blockade that the cancer has set up. And he had four different clients in four different immunotherapy clinical trials in which his client was the only complete response in the trial with thirty some patients. And the odds of that being a coincidence are astronomical.

DrMR: Sure.

DrDM: And he uses diet and lots of herbs, tinctures, powders smoothies and capsules. And he knows a tremendous amount, and he’s highly intuitive. And he encourages patients to trust their intuition as well. But all four of those were the only complete response.

And a complete response is probably a cure. We don’t have enough time, we don’t have 20 years of experience yet to know that for sure. But they are very, very durable. And when they do relapse, they can be retreated with different immunotherapy and respond again at a very high rate.

So that would be the first question I would ask. If you have a cancer that doesn’t have curative therapy and you haven’t been treated yet, the first question I would ask is, “Is there an immunotherapy that is approved for my type and stage of cancer?”

And if they say, “Yes, but it’s only approved if you’ve failed two lines of systemic therapy,” they can say, “The tide is shifting in this direction.” They can say, “Well, I categorically refuse to have chemotherapy.”

And then they say, “Oh, well, in that case, you’re a candidate for immunotherapy.” But if they didn’t know to say that, they would get two lines of chemotherapy and get the immunotherapy after they had failed two lines.

Curable Cancers

DrMR: And I’m assuming the details here matter in terms of if the chemotherapy was shown to be curable, then you are recommending going forward with the chemotherapy. But if it was not, you would recommend the immunotherapy. Or would you modify that at all?

DrDM: No. I think in broad strokes, yes, that’s true.

DrMR: Okay. And if it’s curable, anyway, I think we need to define that. Is there a certain percentage or range of response that is considered curable and it delineates from non-curable?

DrDM: Well in general terms, about 3% of metastatic cancers are curable with chemotherapy, and about 12% are curable with some combination, either radiation alone or radiation and chemotherapy. So that’s all your lymphomas and leukemias and testicular cancer. Those make up about 3% of cancers. So it’s a small percentage. But I’ve seen people with those cancers avoid treatment and then end up dying needlessly.

DrMR: Gotcha. And when we say something is curable, does that mean we are approaching 100% cure rate?

DrDM: In some cases, like non-Hodgkin’s lymphoma, it depends a lot on the subtype and the stage and the grade and so forth, but in very rough terms, they are about 50% curable. It’s about a 50/50 deal. So do the therapy if you’re in the 50% that’s cured. And I think there are things you can do to improve your odds of being in that 50%, with your lifestyle, with your diet, with stress management, because all those things play into how well your body can maintain.

When other medicines or energies are killing the cancer, the immune system is able to respond to those. Until those cells die, they have a very effective cloaking device. The immune system is blind and can’t see them. When they die, the immune system suddenly sees them.

But if the immune system is suppressed by the radiation or the chemotherapy because the patient is eating an ordinary American diet, and sedentary lifestyle, and high stress, their immune system is not going to be in as good a condition to respond to those dying cancer cells as somebody who is exercising every day, eating a whole food organic diet, managing their stress both with exercise and other things.

One of the studies that I included in After Cancer Care was a very simple and profound one done by Barbara Anderson at Ohio State Cancer Center with women who had been treated for early stage breast cancer, stage II and III, that means node positive and/or locally advanced. They were in remission, but they were at high risk for relapse. And one-half of them did progressive muscle relaxation.

If you’ve ever had a yoga class, often at the end of it they will go through this process of having you tighten one muscle group in your feet and then relax and moving up the body. It takes about 10 minutes. And the women who were compliant with this and did it religiously had a 60%, not reduced risk, but 60% less relapse. And relapse from breast cancer becomes an incurable situation.

DrMR: Sure.

DrDM: So that’s a bigger effect than chemotherapy and hormonal therapy together in breast cancer. So these things really do matter. And there are the things that people can do for themselves. And their oncologists don’t know about them. It’s not part of their training. They won’t tell them not to do it. But they need to know about it, and they need to do it.

DrMR: Now in terms of the conventional therapies and navigating that sea of options, is there anything else that you would add along with that? And I think that immunotherapy tip is very helpful. Is there anything else that is important for people to be aware of or factor into their plan, more so on the conventional side?

DrDM: As I said before, I think the key thing is really not just taking the first oncologist that you are referred to. Get second opinions. Get third opinions. And choose the one that you really feel you connect to, that you really feel confidence in. I think what kills people with cancer more than anything is fear. And confidence is the anecdote to fear.

Cancer is such a boogeyman in our collective social consciousness because we have all seen people suffer and die from it. We all know someone or we all have someone in our family who has died of cancer. And so immediately when you get that diagnosis, your limbic system goes, oh my God, and sends out all these panic messages. And you get into this fight or flight response.

And your immune system is run by the opposite branch. It’s run by the parasympathetic, which you only get when you are relaxed.  So if people are living in fear, they are turning off their immune system. And that’s why I say confidence cures cancer. It doesn’t matter really what the details are. It’s really that people have confidence.

DrMR: I think that is very well said. And that’s one of the reasons why I don’t take a hard line with diets. And I don’t believe that fear is a good tool to motivate patients into dietary changes, for whatever reason.

DrDM: Absolutely not. We should be working with encouraging people what to eat because of its benefit, not what not to eat because of its dangers.

DrMR: Sure.

DrDM: Now, don’t have the, “Don’t eat sugar. Don’t eat white flour.” “Do eat vegetables. Do eat brightly colored fruits and vegetables.”

Another good tip is fasting during chemotherapy. That dramatically reduces toxicity. I have had some patients who nearly died from their first cycle of treatment, but then fasted for 3 days with their second cycle and breezed through it.

DrMR: Boy, you know what’s funny about that is sometimes I’ve heard the recommendation during chemotherapy since it negatively affects your appetite, eat whatever appeals to you, even if it’s ice cream or whatever, to make sure you get in some calories.

DrDM: That’s bad advice. The nausea and all the side effects that chemotherapy causes is telling you, don’t eat. And that’s good advice because what’s been found is that the normal cells when you fast very quickly go into kind of a hibernating state. They really lower their metabolic rate. And cells are sensitive to most chemotherapies based on how fast they are growing and their metabolic rate.

So the normal cells shut down. The cancer cells can’t do that. They don’t know how to do that. They have no mechanisms to do that. So fasting doesn’t slow them down at all. And so they get the full effect of the chemotherapy, and the normal cells are relatively protected.

DrMR: Right.

DrDM: This came from the work of Valter Longo at the University of Southern California. He started out studying yeast and found that when he restricted the calories, the yeast would live a lot longer. And he has founded a company called ProLon, which has developed fasting mimicking diets. And they are developing them for cancer. But what they found out is that they have to have a different set of foods for each cycle of chemotherapy.

The fasting mimicking diet is very low in protein, very low in carbohydrate. It’s a little bit of fat and essential vitamins and minerals. It’s about 200 calories total for the day. And they’ve made these things taste really good. But what they found is that the body associates the food with the toxicity of the chemotherapy. So they can’t use the foods again. So they are developing a whole range of these fasting mimicking diets for cancer patients to choose from.

And I started recommending that people just drink herbal tea and maybe a little coconut water, a lot of water and a lot of herbal tea the day before, the day of, and the day after chemotherapy. And they tolerated it so much better. Their blood counts were not nearly as impacted. Their energy wasn’t as impacted. They don’t get the mouth sores.

And it depends on their chemotherapy type as to what the spectrum of side effects is, but they’re dramatically lower with fasting. And this is fairly new information that the body associates whatever foods or flavors were there when they got the chemotherapy. So they need to choose a different one the next time. But that’s a big one for people going through chemotherapy.

I don’t recommend it for people who are really underweight and really have such a poor appetite that they are not able to regain the weight by their next cycle. If they are able to regain the weight that they lose by their next cycle, then it works great.

DrMR: Gotcha. And we’ve got Valter Longo scheduled to come on a podcast in a few months. So that will be an interesting conversation to have with him.

DrDM: Yea. He’s really done groundbreaking work.

Natural Therapies

DrMR: And that’s a nice transition into some of the natural therapies. And that was my next question. Just like we went through what are some of the important conventional therapies to at least ensure that your oncologist is acknowledging, are there certain natural therapies?

And this may be a little bit more challenging because I am assuming there is a litany of natural therapies. But if someone is trying to figure it out, are there some key indicators, some key questions I can ask my natural provider to kind of assess their competency? Of is there anything like that that could be useful? What would you offer people as we wade into the natural sea of options?

DrDM: You know, as you said, there is a huge number of things. Some of the major players, of course, are curcumin or turmeric. There are scientists at M.D. Anderson who have really pioneered the research in that told me that in vitro in cell cultures, curcumin is 50 minutes as potent as turmeric. But in vivo, like in a mouse model, they are equally potent, because there are so many other things in turmeric. So really either one works well.

And cancer thrives on inflammation. And all of your cancer therapies that we use, including immunotherapy, are inflammatory. So I really emphasize herbs that help support a healthy inflammatory response and help move people out of the chronic inflammatory response.

DrMR: And so would ginger be high on your list there?

GingerDrDM: Well, ginger is very high on the list because it also is a great remedy for nausea and an appetite stimulant. It is a cousin of turmeric. Boswellia is very good, but it’s so threatened in the wild, I hate to recommend a lot of Boswellia until somebody figures out how to grow it sustainably. There are only a few places where that tree grows.

DrMR: Vitamin C, IV vitamin C?

DrDM: Vitamin C and IV vitamin C. IV vitamin C definitely works in some cancer patients. But we haven’t figured out how to predict who they are. So that would be hugely beneficial if we could know. IV high dose vitamin C is actually an oxidative therapy. We think of vitamin C as an antioxidant. But given in high doses intravenously, it’s actually an oxidative therapy.

And the same is true of alpha lipoic acid. This was only recently recognized that IV alpha lipoic acid switches in 600 mg dosage therapy that Burt Berkson does in New Mexico. Alpha lipoic acid is a great antioxidant, but given IV it is actually an oxidative therapy. And cancer cells are more sensitive to oxidation. They have less ability to tolerate oxidative stress than normal cells. So that’s why these kinds of IV therapies can work when they work.

And you know, oncologists are very afraid that if cancer patients take any antioxidants that it will interfere because one of the mechanisms of chemotherapy is to create oxidative stress. So IV vitamin C, IV alpha-lipoic acid is sharing that mechanism with many chemotherapy agents.

Treatment

And I have heard radiation oncologists tell their patients don’t eat blueberries or kale because they are too strong and interfere. And we do know that the mechanism by which radiation kills cancer cells is by generating oxygen free radicals. But my analogy is that any antioxidants that you can eat or take would have an effect on radiation like throwing a pillow in front of a freight train.

DrMR: Sure. [Laughs] Good analogy.

DrDM: It’s only in children that have been given really large doses, because they are tiny, by their parents, that there has been documentation that antioxidants in large doses orally in small people can interfere with radiation. And they have kind of generalized, so it has just become dogma in radiation oncology training that patients stay away from antioxidants.

I don’t even like the term antioxidant. I prefer to just say redox active because everything is oxidation and reduction. It’s a reaction that goes both ways. I often will supply ubiquinol as the most bioavailable form of CoQ10, which is a fundamental antioxidant in the mitochondria.

Mitochondria are easily damaged. And that’s part of the post-cancer fatigue syndrome because mitochondria don’t have good DNA and repair mechanisms as the nuclear DNA does. So they are quite vulnerable. And protecting mitochondria can be quite helpful in people’s quality of life post-therapy.

DrMR: Two questions for you. If someone is trying to ascertain, and I know it may be hard to give a general answer here, but they are doing chemotherapy or maybe immunotherapy, and they are wondering should they be taking high dose ginger and vitamin C IV or oral, and CoQ10? Do you think it’s a good idea to wait until after that course of conventional therapy, or is it better to do this at the same time, or is not that simple?

DrDM: It’s not that simple. The basic answer is that we don’t know. I combined those therapies with chemotherapy when I was practicing, and as I said, I had good results. But there are things like selection bias and operator attitude and so forth that play into the results that people have. So it’s a very complex question. I would just encourage people to follow their intuition. Try to find an oncologist who is open to them doing whatever.

Curative Intent Treatment

And there’s another issue. And this is one thing I spend a lot of time training doctors and other practitioners who are working with cancer patients on the integrative side. There is an enormous difference between what we can and should do when patients are being treated with curative intent and when they are being treated with palliative intent.

And if they are being treated with curative intent, I really favor a minimalist kind of intervention. It should be really focused on good diet and very focused on good exercise appropriate to their age and condition. It should be really focused on stress management and body-mind therapies, things like acupuncture. I would be very careful with supplements because even in the most curable cancers, it’s not 100%.

So if you have a stage I Hodgkin’s disease and your patient is that 1% who isn’t cured and you gave them a whole lot of supplements, that may or may not have anything to do with them being in that 1% that wasn’t cured. It may have just been the genetics of their cancer or the microenvironment of their body or their genetics. But everybody is going to feel bad about it.

So if people are being treated with curative intent, I tend to recommend against very much supplementation, maybe vitamin D and omega-3 fatty acids. Those are pretty clearly harmless and helpful. But I always stop supplements the day before, day of, and day after chemotherapy of that sort, because we just can’t predict what sorts of interactions there might or might not be.

If they are being treated with palliative intent, like they have a stage IV cancer that it is not a testicular cancer or a lymphoma that is potentially curable, then I think it is absolutely silly to tell them that they shouldn’t take this or take that. They should take anything that they feel drawn to take or do.

Diet

Vegiterian DietDrMR: Sure. And regarding diet, there are different camps. There are some who recommend a ketogenic type diet, some who recommend a vegetarian and plant-based diet. It sounds like the fasting mimicking diet is kind of a combination of I guess you could say low carb, low calories.

DrDM: Well, the fasting mimicking diet is not something that you can do for long. It is not sustained. A ketogenic diet I think is quite good for an early just diagnosed cancer that hasn’t been treated, to go along with treatment, especially glioblastomas.

One of my mentors was Emmanuel Revici. I studied with him for six years. And he discovered a dualism within cancer, which is not generally appreciated in mainstream or even the integrative world. And he used the general terms anabolic and catabolic to describe this dualism.

And the cancer always starts off anabolic. And in its late stages of its natural history, it often shifts to catabolic. Or after it’s been radiated, it will always become catabolic. And when it recurs, it is often catabolic. And ketones are catabolic substances. And so they are very good for anabolic cancers. And virtually all of our animal models are anabolic models.

If you have a situation where there is weight loss, edema, these are key signs that this is a catabolic state that the cancer is in. And a ketogenic diet will make that cancer worse. That has been my experience as well. So yes to ketogenic diet in early cancers along with treatment, and then shift out of it, because especially radiotherapy is going to push them catabolic. It is a very catabolic therapy. Most chemotherapy is as well.

And most cancers that relapse…I mean, at least we have ways of measuring it and quantitating it and so forth. But in general terms, they tend to come back with the opposite imbalance that they started out with. So the things that were good for them, in the beginning, become bad for them later on. So I would use the ketogenic diet early and then stop it after treatment.

DrMR: Interesting. Okay, I hadn’t heard that before. That is very helpful. Thank you.

DrMR: Regarding mitochondrial damage, we recently had Dr. Jon Kaiser on the podcast, who has done some interesting research in mitochondrial function. And he has a compound on his K-PAX, which is essentially a multivitamin combined with, I believe, four fairly fundamental mitochondrial supports. I know CoQ10 is in there, alpha-lipoic acid, and I am unclear of the other two off the top of my head. But do you have any familiarity with the K-PAX formula specifically?

DrDM: I don’t know that line. But it sounds reasonable.

DrMR: Okay, good. And so you would be running the mitochondrial therapy post chemo.

DrDM: Yea, maybe even in between cycles, to support the mitochondrial recovery.

DrMR: Gotcha. Okay. That takes us through many of the things I wanted to at least touch on and actually provided many other tips I wasn’t even sure we would be able to pull out of that brain of yours with this wide wealth to pull from. So I’m very appreciative.

Natural Therapies

Is there anything that you would like to offer the audience as we draw to a close? And then after that, would you please tell people if you have a website or any other literature that you would point them to if they wanted to learn more?

DrDM: I don’t have a website. Oh, I should mention that my friend, Nalini Chilkov, who is an acupuncturist and herbalist in Santa Monica, very accomplished in the integrative cancer space, has an online training course, a basic course on integrative cancer therapy. It is a great place for docs, herbalists, anyone who is interested in getting more into the integrative cancer space. Contact her office and find out how to get into that course. That’s a good resource.

I think fundamentally we have made a huge error by approaching cancer with a military and war mentality. I think cancer is trying to send a message to us about what we are doing wrong personally and collectively. And we have learned so much from it. I think we should stop fighting it and really start studying it and listening to it. I should write another book called Listening to Cancer.

The war mentality also brings up the whole sympathetic nervous system. And the healing is in the opposite. It’s in the parasympathetic. It’s in the relaxation. It’s in the love and appreciation. And one of the gifts of cancer is really we’re all going to die, right? None of us gets out of here alive, as somebody said. We get a pretty long heads up.

So when it becomes clear that people are going to die from this process, they have time to spend with friends and family and resolve unresolved things and forgive. I also think that active forgiveness is a huge part of therapy, because resentment is a carcinogenic emotion. I am quite clear about that from forty plus years in the field. So not forgiving somebody only hurts the person holding the grudge. And when your life is on the line, it’s really important to forgive.

But when you drop over from a heart attack or a stroke, you don’t get that. You don’t get a chance to say goodbye. You don’t get a chance to resolve unresolved conflicts or tell people how much you love them. And cancer does allow that. So I think we just really need to shift our perspective collectively, and I think we would do a lot better.

Treatment

DrMR: I think that’s pretty sage advice. Anything that we can do to take stress off of someone, it certainly only stands to at least be neutral, if not positive, in terms of how it impacts their health and their psyche.

DrDM: Exactly.

DrMR: Well, this has been, like I said a moment ago, a fantastic call. I really think you have provided people with some key navigating stars, if you will, to guide them along this process, which I’m sure is quite stressful. And it is hard to determine what to do and where to go and who to trust.

Beta-Blockers

DrDM: You just reminded me of another pearl. When people are diagnosed with cancer, especially if it’s a significant cancer, that is probably the most stressful event of their life. And we have talked about the effects of stress.

I have found, and it has been noted, that people who are taking non-selective beta-blockers for other conditions like high blood pressure or atrial fibrillation, who have cancer, have way better outcomes. And so I about seven or eight years ago, maybe ten, started recommending that people when they are diagnosed with cancer, get someone to prescribe Inderal, beta block selective, 40 mg twice a day, if they can tolerate it.

You can start with 20 and increase to 40 if they can’t. If they have really low blood pressure, they may not be able to take as much. But pharmacologically blocking the sympathetic nervous system dramatically protects them from that and allows their parasympathetic nervous system to function while they are navigating all the visits to the medical oncologist, radiation oncologist, surgical oncologist, and so forth.

It’s an incredibly stressful time. And nobody can really figure out through their own stress management practices in that period of time how to protect themselves. So I think that is a very valuable medication in protecting them. And then, later on, I encourage them, once they have established a stress management–and I have outlined sort of a menu that people can choose from in After Cancer Care–and then taper off of it. They don’t need it later on if they can develop a good stress management program of their own.

But it hasn’t been done in a clinical trial yet. But looking at it just in population studies, people on non-selective beta blockers have far better outcomes than those who aren’t. And it has been documented also in animal models. So there is good evidence for it. And it’s a very simple thing to do.

DrMR: Great. Well, one more pearl for the list here.

DrDM: Yea. Thank you. Well, you triggered that in your closing comments. So I wanted to throw that in.

Episode Wrap Up

DrMR: Awesome. Well, thank you. Thank you so much for taking the time. Boy, this has been a very enlightening call. And I really appreciate you and the work that you are doing. So thank you again.

DrDM: Great. I really enjoyed it. I don’t have a website. And I retired from integrative cancer consultation. Please don’t try to find me. But there are people out there that I have trained who are very good. And there are more and more people coming into the space all the time. And I think the whole profession is going to move in that direction over the next 20 years. And I hope I am around to see it. I celebrate my 70th birthday in a couple of weeks, and I’m hoping for 20 more. And I think it’s going to be a really exciting time.

DrMR: Awesome. Happy early birthday! And I hope you are right. And I have a good feeling based upon some of what you have said that we are getting closer to a much more leveraged relationship with cancer here. All right, sir. Well thank you again. And have a safe flight.

DrDM: Okay. Thank you.

DrMR: All right. Take care. Bye, bye.

DrDM: Bye, bye.

How to rein in the widening disease definitions that label more healthy people as sick

How to rein in the widening disease definitions that label more healthy people as sick

May 16, 2017 6.10am AEST

The experts arbitrarily and controversially created a new cut-off for diagnosis that classified more than a quarter of all post-menopausal women as having the “disease”. The following year (1995) pharmaceutical company Merck launched Fosamax, a drug for osteoporosis that would soon become a multi-billion-dollar blockbuster.

In 2008 a guideline from the United States National Osteoporosis Foundation further increased the numbers of those diagnosed, with a recommendation that more than 70% of white women over 65 should take osteoporosis drugs. With medication, of course people benefit by avoiding a fracture. But many of those at low risk will suffer more harm than good, unnecessarily taking potentially harmful drugs.

Osteoporosis is just one condition that has had its definitions widen over time and, with that, the pool of people diagnosed as having it. An article published today in the journal JAMA Internal Medicine outlines the first serious attempt to set some global rules for those experts who move diagnostic goalposts that label more people as sick.

Medical panels are constantly changing diagnostic cut-offs and lowering thresholds to classify many conditions and diseases. Those changes determine whether we or our loved ones receive a diagnosis that might help us – by, for example, giving us access to a life-saving treatment – or harm us – by bringing the anxiety, cost and danger of an unneeded medical label.

Osteoporosis has had its definitions widen over time and, with that, the pool of people diagnosed as having it. from shutterstock.com

New ‘pre’-diseases

Widening disease definitions have been central to the problem of overdiagnosis, where classifying previously healthy people as sick can lead to more harm than good.

For instance, minor memory or cognitive changes are increasingly being seen as symptoms of a condition called “pre-dementia”. This label can potentially be applied to a third of people over the age of 65. Some of them may never have dementia, yet are faced with the anxiety and stigma of a possible, eventual diagnosis.

Another example is the emergence of “pre-diabetes”, which labels 30% to 50% of all adults, depending on the diagnostic criteria used. “Pre-diabetes” is a controversial term used to describe a blood sugar level above normal, but below that of someone with diabetes.

While some argue the label may bring benefits – for example, by encouraging healthier lifestyles – such a dramatic widening could do much harm. As one article in the BMJ journal states:

A label of pre-diabetes brings problems with self-image, insurance and employment as well as the burdens and costs of health care and drug side effects.

Then there’s gestational diabetes – the type diagnosed in pregnant women. In 2010 a global panel – which influences how the condition is diagnosed in many places, including Australia – recommended changes to the diagnosis that would double or even triple the numbers of pregnant women labelled. The decision was taken on the basis of new evidence suggesting benefits for mother and baby diagnosed at the new lower thresholds.

Yet when an independent group convened at the United States National Institutes of Health in 2013 took a close look at the 2010 decision, they rejected it. The reviewers cited a lack of convincing evidence newly diagnosed women would benefit from treatment. They also raised concerns about additional costs to the health system, and unintended consequences of labelling, such as an increased rate of caesarean births and related patient costs.

Pre-diabetes is used to describe a blood sugar level above normal, but below that of someone with diabetes. from shutterstock.com

Reforming new diagnoses

A recent study of changes to the definitions of more than a dozen common conditions, including high blood pressure, depression and asthma, found three things.

First, the expert panels of doctors who made these changes often decided to widen definitions classifying more people as patients. Generally, the motivation was that treating milder problems, or finding diseases earlier, would benefit the newly diagnosed.

Second, these panels did not rigorously investigate the downsides of that expansion; none examined how many people would be overdiagnosed.

And, third, most panel members had financial relationships with drug companies that stood to benefit from panel decisions.

Following that study, a global body that sets guiding rules for these panels – the Guidelines International Network – set up a working group in 2014 to consider the problem of widening disease definitions. It included members with a range of experience, from genetics to guideline development, as well as from the World Health Organisation.

Following a review of the literature and consultation, the group created a short common-sense checklist of questions being published today in JAMA Internal Medicine. These questions are intended for expert panels to think about, before they decide to widen definitions and move the medical goalposts. Some of them include:

  • What are the differences between the old and new disease definition?
  • How will the new definition change the numbers of people diagnosed?
  • What are the potential benefits for those classified under the new definition?
  • What are the potential harms for those diagnosed and society?

This new guidance might seem somewhat abstract. But it directly affects all of us. The next step is to test how the new guidance works in practice, where panels of experts are actually considering a change to a disease definition.