Estrogen and aromatase – Keeping the wolves from the door.

Estrogen and aromatase,  (and the  role of prolactin and a lack of progesterone) in cancer are well documented and so are the stimulatory effects of the neuro-endocrine (nervous system/hormones) disruptors termed xenoestrogens, which mimic the action and excess of estrogen (Kim, Kurita, & Bulun, 2013) (Mungenast & Thalhammer, 2014). Estrogen and notably estradiol/E2 is often measured by a standard blood test, which remains as problematic as other blood tests such as TSH, which I have previously described.

“ At first, it was assumed that the amount of the hormone in the blood corresponded to the effectiveness of that hormone. Whatever was in the blood was being delivered to the “target tissues.” But as the idea of measuring “protein bound iodine” (PBI) to determine thyroid function came into disrepute (because it never had a scientific basis at all), new ideas of measuring “active hormones” came into the marketplace, and currently the doctrine is that the “bound” hormones are inactive, and the active hormones are “free.” Ray Peat

In addition to the obvious production of estrogen in the reproductive tissues, it’s possible to increase estrogen conversion via aromatase, an enzyme which converts androgens such as testosterone to estrogen, is one of the other main factors. Adipose tissue is a prime location for increased aromatase activity.

Another problem with measuring hormones in the blood is that it rarely accounts for the intracellular accumulation of hormones. Estrogen in excess in the cell, promotes fluid retention, swelling and causes an increase in calcium. Measuring pituitary hormones and in particular prolactin (PRL) may give us a better indication of the relative excess of estrogen due to estrogens stimulatory effect on the anterior pituitary and PRL.

PRL excess is associated with issues such as breast cancer, prostate cancer, resistance to chemotherapy, infertility in both men and women, male reproductive health and galactorrhea (Sethi, Chanukya, & Nagesh, 2012) (Rousseau, Cossette, Grenier, & Martinoli, 2002). Treating PRL excess, particularly linked to the most common form of pituitary tumour (1:1000), the prolactinoma is often treated effectively by the dopamine agonists Bromocriptine or Cabergoline. However, it’s not beyond the realms of possibility that prevention and treatment of excess PRL production, be achieved with decreasing synthesis and exposure to estrogens both endogenous and from external sources.

Myopic thinking.

Modern medical thinking and analysis has led us to a reduced proposition when it comes to diseases like cancer. Cancer is essentially a metabolic disease, and the proposed respiratory defect, the idea of scientist Otto Warburg, is often replaced by the mechanistic thinking of the receptor theory of disease. Estrogen receptors are one of the main evaluations for assessing types of cancer but the very essence of the testing leads us to an increased myopic line of questioning, failing to ask the necessary questions that underlie a persons health status.

If a city is being evacuated, its railroad transportation system, will be quickly “saturated,” and the impatience of a million people waiting for a ride wont make much difference. But if they decide to leave on foot, by bicycle, boat or balloon, in all directions, they can leave as soon as they want to, any number of people can leave at approximately the same time. A non-specific system is ‘saturable,” a nonspecific system isn’t saturable. The idea of a cellular “receptor” is essentially that of a “specific” transport and/or response system. Specific transporters or receptors have been proposed for almost everything in biology – for very interesting ideological reasons– and the result has been that the nonspecific processes are ignored and supressed. Ray Peat

Solutions.

Sometimes there are minimal opportunities for people to change their environment. Perhaps creating more solutions to enable better conversations with the environment, is the most pragmatic solution available?

Maintaining the body’s production of energy by optimising thyroid production, suppression of TSH (thyroid stimulating hormone) and lowering of other stress hormones like ACTH, intake of carbohydrates, protein and adequate light can support the necessary energy needed for the liver and digestive system to enhance detoxification of estrogen and estrogen mimickers.  A sluggish, fatty or hypothyroid state of the liver, makes it difficult for estrogen to be excreted. In states of constipation, beta glucaronidase converts inactive estrogen to the active form.  Keeping both estrogen and aromatase low seems a step in the right direction.

Foods also have the capacity to enhance estrogen synthesis. Mushrooms have shown to be a potent inhibitor of aromatase enzymes and have the capacity to lower the systemic production of estrogen (Grube, Eng, Kao, Kwon, & Chen, 2001). However it’s important to note that mushrooms need substantial cooking to reduce the liver toxins present.

 
“The hydrazine-containing toxins that Toth and others wrote about are destroyed by heat. Since extracts made by boiling the mushrooms for three hours were very active, I think it’s good to boil them from one to three hours.

If you want to know more about prepping mushrooms and soups, then check out the link below for The Nutrition Coach, who reminded me why mushrooms for lowering estrogen and a great source of protein will be helpful when consumed regularly.

  

References: 

Grube, B. J., Eng, E. T., Kao, Y.-C., Kwon, A., & Chen, S. (2001). White Button Mushroom Phytochemicals Inhibit Aromatase Activity and Breast Cancer Cell Proliferation. J. Nutr., 131(12), 3288–3293. Retrieved from http://jn.nutrition.org/content/131/12/3288

Kim, J. J., Kurita, T., & Bulun, S. E. (2013). Progesterone action in endometrial cancer, endometriosis, uterine fibroids, and breast cancer. Endocrine Reviews. http://doi.org/10.1210/er.2012-1043

Mungenast, F., & Thalhammer, T. (2014). Estrogen biosynthesis and action in ovarian cancer. Frontiers in Endocrinology, 5(NOV). http://doi.org/10.3389/fendo.2014.00192

Rousseau, J., Cossette, L., Grenier, S., & Martinoli, M. G. (2002). Modulation of prolactin expression by xenoestrogens. Gen Comp Endocrinol, 126(2), 175–182. http://doi.org/10.1006/gcen.2002.7789\rS0016648002977890 [pii]

Sethi, B. K., Chanukya, G. V, & Nagesh, V. S. (2012). Prolactin and cancer: Has the orphan finally found a home? Indian Journal of Endocrinology and Metabolism. http://doi.org/10.4103/2230-8210.104038

http://raypeat.com/articles/articles/pdf/Estrogen-Receptors-what-do-they-explain.pdf

http://www.thenutritioncoach.com.au/anti-ageing/how-i-prep-mushrooms-and-why-its-worth-the-bother/#more-2595

 

Osteoporosis- could your exercise, nutrition and medical advice be better?

Osteoporosis and bone health, like many other aspects of optimal biology is a product of an organisms inputs and reactions to environmental stimulus. Osteoporosis is a condition like others, where prevention is often easier than the cure but perhaps the cure has been overcomplicated? Osteoporosis is a multifactorial musculoskeletal disease that is usually associated with the ageing process, decreased bone mineral density (BMD) and its tendency to fracture easily.      

It’s clear that a number of factors that can be maintained throughout life to reduce the incidence of Osteoporosis in both men and women. Before we review those and compare with current guidelines, here’s some background info on the subject.

Primary Osteoporosis is the age related decline in men at around 70 and suggested as being a postmenopausal state, induced through the decreased production of estrogen in females. This last point is accepted in medical literature as the main cause of osteoporosis in females but may be severely flawed (more on this point later).

Secondary osteoporosis can be related to the following factors

Hypogonadism – testosterone/estrogen deficiency
Endocrine disease – Cushing’s syndrome, acromegaly, thyrotoxicosis, Addison’s disease and hyperparathyroidism
Dietary or assimilation deficiencies of calcium, vitamin K, vitamin D and other nutrients
Inflammation-rheumatoid arthritis, systemic lupus and ankylosing spondylitis
Neoplasms- Myleoma, lymphoma and leukaemia
Reduced physical activity
Medical drugs – corticosteroids, antiretroviral, antipsychotic, chemotherapy, hormone therapy, nicotine and excessive alcohol
Family history/genetics
Diabetes

The financial burden from osteoporosis generally, will increase from 98 Million Euros to 121 billion with proportional increases of 27.5 million to approximately 34 million people between the years 2010 to 2025 (Hernlund et al., 2013). Despite these huge burdens there appears to be a lack of well-designed educational programs that are geared at prevention of osteoporosis through non-pharmacological means.

The supplementation of vitamin D and calcium are well documented in osteoporosis strategies but a strategy to avoid these states are diets containing adequate calcium, vitamin A, K, magnesium (and others) adequate sunlight and moderate exercise.

Ok, so there’s a problem, it’s big business and there’s a lot of great info on how to avoid it right? Well no and here are the major points why I believe its not.

Diagnosis

 Dual energy X-ray absorptiometry (DEXA) is the recommended choice for osteoporosis diagnosis, serum calcium, phosphate, creatinine (with GFR) alkaline phosphatase, liver function, 25 OHD, total testosterone, estrogen CBC and 24 urinary calcium excretion are recommended for the interpretation of secondary causes of osteoporosis (Watts et al., 2012).

Hormones

Estrogen loss is touted as the most significant factor in decreasing BMD yet it’s action only retards resorption, or the removal of calcium from bone. Estrogen tends to inhibit the action of osteoclasts which ultimately reduce BMD. It’s the main reason the introduction of hormone replacement therapy (HRT) was considered as the primary treatment until its long-term use was found to induce clotting and cancer in women. So estrogen does not reverse Osteoporosis, it prevents further bone loss.

A variety of studies have suggested little influence of testosterone in males on BMD and that low estradiol levels combined with elevated sex hormone binding globulin appear to increase the loss of BMD (Cauley et al., 2010). A point worth noting from the correlation associated with higher estradiol levels and decreased BMD loss is that all participants in the study were recorded as having increased weight and BMD, which may influence skeletal modelling due to increased bone-loading parameters. Perhaps too much emphasis has been given to the suggestion that estrogen and its primary role of tissue proliferation amongst others, which should follow the course of age related decline?

Progesterone on the other hand has been shown to be a bone trophic or building factor that increases mineralisation of BMD, via osteoblasts (Prior, 1990). Stress increases cortisol and decreases progesterone binding at the receptor, with a preference for the glucocorticoid. Ray Peat (1997) points out that cortisol causes bone loss and its widely accepted that progesterone has an “antiglucocorticoid” action, it is reasonable to think that progesterone should protect against bone loss, and that it is a progesterone deficiency after menopause which is a major factor in the development of osteoporosis.

Thyrotoxicosis has been suggested as a mechanism of bone resorption but this appears inaccurate-  Ray Peat does a much better job at explaining this.

Medical treatment

Bisphosphonates are the first line medical treatment for treating osteoporosis and show modest changes to hip and vertebral BMD over 3 years. There use may come at a risk. Gastro intestinal side effects are well documented and in some the increase of osteonecrosis of the jaw has been observed. In some, the long-term use has been shown not only to increase the rate of fragility fracture but also to inhibit the healing process. It should be noted that adequate calcium and vitamin D in the diet are essential for bisphosphonate effectiveness

 Nutrition

 There tend to be two well-known stances to the fitness industries approach to nutrition. One, the transformation approach, where limiting of nutrients, particularly dairy and carbohydrates and intermittent fasting are the norm. Another, the holistic warrior whose consumption of chia seeds and all things green, raw and limiting of dairy and sugar again,  may be a factor into lowering BMD in later life. Calcium is an essential nutrient for bone health and dairy is indeed a great source of calcium. Here’s an old blog on the subject.

 It’s clear that adequate vitamin D is a nutrient that is important in BMD maintenance. It regulates calcium levels, decreases the production of parathyroid hormone, which is a potent resorption factor of skeletal calcium when calcium or vitamin D are low. Here are the main points that relate to diet.

  • Vitamin D in isolation and particularly high doses increases fracture rates (Janssen, Samson, & Verhaar, 2002)
  • Unless vitamin D is accompanied by adequate calcium, BMD can decrease further.
  • Vitamin K2 can prevent the calcification of soft tissues and help improve blood calcium levels (Masterjohn, 2007)
  • High meat and diets high in pulses and beans can have a negative effect on calcium levels due to their high phosphate levels.
  • Unless you assess other key nutrients like magnesium and the factors discussed above
  • Low diary intake can be associated with poor bone health.
  • The low carbohydrate, raw green and seed eating diet suggested by holistic health practitioners may contribute to lower BMD.

Exercise

Regular exercise has been touted as a significant factor in maintaining muscle mass and increasing BMD. But is the type of exercise that people are doing, increasingly in their younger years, contributing to better or worse outcomes to BMD. For bone to form adequate carbon dioxide (CO2 ) is essential. Some exercise regimes are so challenging, they contribute to excess levels of metabolic acidosis (lactic acid) and passing of CO2 from the body (worth noting that sugar consumption can also help to increase CO2 production) . Perhaps for exercise to be effective it should be light to moderate, with adequate rest periods that don’t mean that the participant is lying in a pool their sweat and vomit.

Walking, strength training with adequate rest, yoga, Pilates and other modes of moderate exercise appear most suitable for modest improvements to bone health but the diet and hormone factors are key.

It’s clear that osteoporosis is in the rise but it can be reversed. But instead of heading advice like cutting out dairy, eating lots of uncooked vegetables and training to complete exhaustion. There are more suitable mechanisms for improving bone health

References:

Cauley, J. A., Ewing, S. K., Taylor, B. C., Fink, H. A., Ensrud, K. E., Bauer, D. C., … Orwoll, E. S. (2010). Sex steroid hormones in older men: longitudinal associations with 4.5-year change in hip bone mineral density–the osteoporotic fractures in men study. The Journal of Clinical Endocrinology and Metabolism, 95(9), 4314–23. http://doi.org/10.1210/jc.2009-2635

Hernlund, E., Svedbom, a, Ivergård, M., Compston, J., Cooper, C., Stenmark, J., … Kanis, J. a. (2013). Osteoporosis in the European Union: medical management, epidemiology and economic burden. Archives of Osteoporosis, 8(1–2), 136. http://doi.org/10.1007/s11657-013-0136-1

Janssen, H. C. J. P., Samson, M. M., & Verhaar, H. J. J. (2002). Vitamin D deficiency, muscle function, and falls in elderly people. The American Journal of Clinical Nutrition, 75(4), 611–5. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11916748

Masterjohn, C. (2007). Vitamin D toxicity redefined: Vitamin K and the molecular mechanism. Medical Hypotheses, 68(5), 1026–1034. http://doi.org/10.1016/j.mehy.2006.09.051

Peat, R. (1999). Thyroid Therapies, Confusion and Fraud. Retrieved from www.raypeat.com/articles/articles/thyroid.shtml

Prior, J. C. (1990). Progesterone as a bone-trophic hormone. Endocrine Reviews, 11(2), 386–398. http://doi.org/10.1210/edrv-11-2-386

Watts, N. B., Adler, R. A., Bilezikian, J. P., Drake, M. T., Eastell, R., Orwoll, E. S., & Finkelstein, J. S. (2012). Osteoporosis in men: an Endocrine Society clinical practice guideline. The Journal of Clinical Endocrinology and Metabolism, 97(6), 1802–1822. http://doi.org/10.1210/jc.2011-3045

Estrogen and Progesterone

For the general public there is often no real need to understand what hormones are or what they do, unless faced with specific problems related to them. As hormones are affected increasingly by our environment, which includes: Food, air, water, physical and psychological stress, it seems that a basic understanding of problematic hormones can be helpful for maintaining or improving health.

Before I attempt to give a brief overview of a complex subject, here are a few terms to be aware of, mainly related to female function.

Follicular phase- first 14 days of cycle to ovulation and increased production of estrogen, primarily E1

LH- Luteal phase, last 14 days, corpus luteum, which increases progesterone

Progesterone- Hormone of gestation, bone formation, anti clotting concerned with cell differentiation.

E1-E2-E3 – Estrogen classifications of Estrone, Estradiol and Estriol. Estrogen promotes growth and becomes problematic in the face of increased cellular division and changes or mutations.

Xenoestrogens – synthetic estrogen like compounds found in plastics, contraceptives, fuel and industrial waste. These have the capacity to increase estrogen levels in men, compounding issues related to testosterone function.

Progestin- synthetic progesterone. Lacking in the benefits of natural progesterone and increases unwanted symptoms.

CYCLEovul

Estrogen’s primary role is one of growth. It is used to stimulate growth of tissue, especially so in the endometrium. During the follicular phase estradiol increases and just before ovulation starts to decrease. Progesterone’s protective effects are enhanced via increased production of the corpus luteum.

Problems with excess estrogen have increased due to changes in diet, increased exposure to environmental pollutants and other factors that are not offset by increased production of progesterone. Below are just some of the actions of both estrogen and progesterone.

Effects of Estrogen Effects of Progesterone
·      Breast stimulation·      Endometrial proliferation

·      Increased body fat

·      Salt/ fluid retention

·      Clotting

·      Depression

·      Headaches

·      Decreased libido

·      Impairment of blood sugar

·      Reduced oxygen

·      Risk of breast cancer

·      Osteoporosis

·      Decreased thyroid

·      Increases CV issues.

·      Anti tumour effects·      Supportive to fertility

·      Sedative effects

·      Improves blood sugar

·     Decreases  Ovarian cysts

·      and Menopausal flushing

·      Removal of facial hair

·      Decreased Menstrual cramping

·      Improved auto-immune

·      Hormonal balance

·      Anti -Stress

·     Decreased arthritis

·      Promotes sleep

·      Thickens hair on head

 

 

 

Balancing blood sugar levels, particularly an issue during pre-menses, can be achieved with Progesterone. Hypoglycaemia is often present (especially so when engaged in exercise, low carbohydrate or calorie consumption) and particularly when oxidative damage occurs to cellular function, oxygen use is decreased and therefore a reliance on glycolysis, a sugar using energy system, which creates an abundance of lactic acid, occurs. Elevated levels of lactic acid are problematic, not only to cellular function but are also inefficient means of energy production. It’s transportation and conversion back to glycogen requires much more energy than it produces. Progesterone protects against estrogen’s anti-oxygen effects.

Progesterone is non-toxic even at elevated levels, however anaesthesia and euphoria has been recorded, along with changes to the menstrual cycle which can be noted as mainly positive. Symptoms related to PMS have often disappeared and its use is recommended only between ovulation and menstruation. Estrogen/progesterone balance can be achieved by supplementation, however diet can help to facilitate the change and serve to maintain the gains achieved with progesterone supplementation. In many cases decreased thyroid allows for excess estrogen in the body, via mechanisms of decreased energy to detoxify, which include liver and digestion mechanisms. The reverse can also be true due to increased estrogen decreasing thyroid function

Excess stress can be the cause of decreased progesterone and increased estrogen’s, increased cortisol and decreased thyroid. The use of adequate protein within the diet and carbohydrates will ensure that thyroid is provided efficiently. Daily sunshine helps to promote optimal progesterone conversion, in addition to supplementation and those who live in areas with less sunlight should also consider progesterone supplementation.

During pregnancy, progesterone production can be one hundred times more than the amount seen during the premenstrual phase. A lack of progesterone during pregnancy has been associated with toxaemia. Symptoms include high blood pressure, excessive weight gain, oedema (fluid retention) and protein loss in the urine. If excess progesterone is available, the mother will simply use it, therefore an excess of progesterone would be preferred to a deficit and the likelihood of toxaemia induced by too little progesterone. Progestins seem to make many unwanted symptoms much worse

It is clear that decreasing exposure to environmental pollutants is helpful to lowering xenoestrogenic load. Foods that contain natural phytoestrogens can also affect estrogen/progesterone balance and where symptoms exist decreasing foods such as uncooked brassica vegetables, soy, nuts and seeds would be helpful in attempting to restore balance.

References:

Dalton, K The Menstrual Cycle.

Lee, J. Natural Progesterone, Multiple roles of a Remarkable Hormone. BLL Publishing

Peat, R. Nutrition for Women.

Tonilo, P.G. Endogenous estrogens and breast cancer risk: the case for prospective cohort studies. Environ Health Perspect. 1997 Apr;105 Suppl 3:587-92.

Online references:

http://raypeat.com/articles/articles/progesterone-summaries.shtml

http://raypeat.com/articles/articles/estrogen-age-stress.shtml

 

 

Calcium- Don’t ditch the dairy.

Calcium – don’t ditch the dairy.

Like every nutrient that we have consumed over the last millennia or ten, there are reasons why some foods appear more beneficial than others. Using poor tests like Igg4 sensitivity/allergy analysis many ‘experts’ have convinced us that one of our most potent foods is causing us more harm than good. I am on the bandwagon that as far as my food goes (meat and dairy) grass fed, free range and organic remain a better choice for all concerned. Hormesis can only take us so far when it comes to pesticide and pollutant exposure and the individuality of tolerance and adaptation remains a knife-edge for many.

Don't ditch the dairy

Don’t ditch the dairy

Without getting into the arguments of which type of cows produce what compounds. This topic is merely aimed at why people have issues with calcium uptake and is the problem really a dairy issue?

Many people who have had blood tests are often told to take extra calcium supplements in response to presenting with low serum calcium. However the issue of lowered calcium in the blood may have nothing to do with the amount of calcium that they are ingesting. Here are some potential mechanisms:

• Low levels of vitamin D: Vitamin D is a well-known nutrient/hormone like substance that allows for the adequate uptake of calcium into bones and teeth. amongst many other functions which include immune system function. (This synergistic relationship can be observed in reverse also)
• High phosphorus/phosphate diet. In addition to the added phosphates to foods and crops. Current recommendations suggest increasing portions of grains, beans and peas, which not only contain phosphates but also contain phytates, which can block mineral uptake. Low magnesium is also an issue.
• Increased estrogens and xenoestrogens that increase the stress response and cause calcium to leach from the bones into soft tissues. A decrease in available progesterone can decrease bone density.
• Poor reabsorption factors such as low intake of vitamin K2
• An actual calcium deficiency from low calcium intake
• Excessive exercise which can be due to inadequate calcium and poor carbon dioxide retention.
• Inability to absorb calcium from the digestive tract, low stomach acid levels/hypochlorhydria and damage to villi/intestinal lining, which can be observed in celiac but increasingly with intestinal hyper-permeability, endotoxin and chemical induced damage.
• Decreased blood albumin levels which bind calcium. Digestion and dehydration issues mainly.
• Regulation of PTH or parathyroid hormone.

Osteoporosis is on the rise but its increasing prevalence is not due to low calcium intakes but due to many complex interactions, between stress, pollutants, low sunlight exposure, excessive exercise and nutrient levels. The common reductionist approach is to throw the same nutrient at the problem in larger amounts and hope that this so called ‘deficiency’ is corrected.

It’s worth noting that elevated serotonin levels in the blood are responsible for bone less. An increase in serotonin  can be viewed with both a temporary spasticity of smooth muscles tissues and loose or watery stools. The role of serotonin is to increase evacuation of the bowel, mediated by an increase in its production from the entero chromaffin cells in the digestive tract, where some 95% of the bodies own supply is created. A diet high in nuts and seeds, which contain serotonin are likely to irritate the digestive tract. From an evolutionary survival perspective, this allows for seeds to be passed out from the bowel without being digested, ensuring plants survival. Increased aggression and irritability have been noted in elevated serotonin levels, which also correlates with a decrease in bone density. Ensuring adequate calcium in the diet during these times is therefore essential.

When phosphorus increases and there is a lack of vitamin D, PTH increases to balance out the need for increased calcium, which is taken from bones and teeth. In essence much of the calcification of arteries and soft tissues can be attributed to this situation. Some of the signs that can be observed with low calcium levels are:

• Muscle cramps
• Nose bleeds
• Soft fingernails
• Frequent cold sores, rashes
• High or low blood pressure
• Irritability
• Fevers with mild colds

Administering calcium supplements to those with calcium deficiency is much like talking over someone before they have a chance to speak. You only here there initial words but fail to here what they are truly saying.

Much of the marketing and sales of supplements these days are suggestive that our food does not give us the nutrients that we need and that we need to stay plugged in to the rattle of supplement bottles opening daily. When in fact if we just strive to improve digestion and cofactor optimisation this simply isn’t the case. In the case of dairy, when we flippantly talk about super foods, when you look at the nutrients provided from dairy, it is indeed a food with plenty to say for itself, particularly in the situations of growth, stability and anti-stress.

References:

1. Christodoulou, S. , Goula, T., Ververidis, A., and Drosos, G. Vitamin D and Bone Disease. Volume 2013 (2013), Article ID 396541, http://dx.doi.org/10.1155/2013/396541
2. Weatherby, D. Blood Chemistry Analysis. Bear Mountain Publishing. 2002.

Online:

http://raypeat.com/articles/articles/phosphate-activation-aging.shtml