depression

The Big Estrogen Hoax

Routine spraying with potent pesticides was deemed safe previously.

Routine spraying with potent pesticides was deemed safe previously.

One of the reasons I decided to pursue a master’s degree in endocrinology was to challenge my own bias and what I had learnt from reading the works of people like Ray Peat PhD and Dr Katherina Dalton. Prior to my thesis I had to undertake a post graduate diploma due to my lack of medical training. It became apparent early on that discussions were heavily centred around endocrine mechanisms that occur in isolation that have become almost indoctrinated throughout text books and the plethora of funded research to support these narratives. My own research investigated the dogmatic belief that thyroid blood tests are accurate when faced with ongoing stress, nutrition and pollution issues that can render such blood tests inaccurate and more often than not appear normal. I thought having better conversations with clinicians might be a positive outcome of this study but anytime I attempt to discuss its always the same deflection that blood tests are accurate. It’s clear they are not in many different scenarios

One of the biggest problems and what could indeed be deemed as the biggest hoax in medicine (although the perpetuation of the need to lower cholesterol levels with statins is on a par with that) is the dogmatic belief that a female becomes estrogen deficient during the menopause. After reading Ray Peat’s PhD thesis and book (Peat, 1997)(Peat, 1972) that stated the counter argument, I’ve tried to look at this argument extensively over the last few years. It seems complex on the outside but consider the following and think about if for a minute or two.

Why is pregnancy protective?

When a woman becomes pregnant, she can produce up to 100 x more progesterone than normal. Why? It’s well known that progesterone is a hormone of organisation. It’s been shown to be associated with differentiation (regulate tissue growth induced by estrogen) compared to estrogen’s action of tissue growth, therefore just like thyroid hormone it’s a potent factor in creating tissue oxygenation and enhances blood sugar regulation. It’s well known that many miscarriages occur in the first trimester due to hypoxia induced by increased estrogen levels. Excess estrogen is also associated with disorganised biology and cancer. We know progesterone is protective and organisational so why does the madness persist that ovarian decline is associated with a lack of estrogen?

Recently I’ve thought about the comparison between economics and environment and how analogous it is with an excess of estrogen. The world needs more progesterone, it’s exposure to estrogen like processes of growth, unrestricted profits and resource draining that is excessive and unrestrained. It needs less leadership, more organisation, more differentiation and more cooperation. So do cells when they are exposed to the same forces.

The biggest study to date assessing the effects of hormone replacement therapy or HRT was the women’s health initiative (Rossouw et al., 2002). The main findings of this study were that HRT increased breast cancer and cardiovascular risk by increasing thrombosis. Further problems were encountered when progestins were added to estrogen replacement therapy.

Now go back and read that last part again because this is where a vast problem exists in medicine and advice given to females. Not just going through menopause but equally any advice they are generally given related to hormone health, effects of contraception etc. Why? Because progestins are not progesterone, they are synthetic versions of progesterone that act very differently to natural progesterone and the real problem is the acceptance by medical practitioners that they are one in the same.

Why so much confusion?

Take the following paper Progesterone action in endometrial cancer, endometriosis, uterine fibroids, and breast cancer by Kim et al (Kim, Kurita, & Bulun, 2013). This is a well-respected group of progesterone researchers who do make the distinction that progesterone antagonizes estrogen driven growth in the endometrium and that insufficient progesterone increases endometrial cancer. Throughout the paper they often cite the negative effects of supplemental progesterone (particularly with breast cancer) combined with estrogens that increase the progesterone receptor (PR) and increase cancer growth. Yet all the studies cited have used progestins and not natural progesterone. This is a primary factor in the perpetuation of mass confusion between progestins and natural progesterone.

Not that the receptor is a great way to test a hormones actions and in particular the PR can be stimulated by estrogen, other hormones such as cortisol and like other receptors can be hijacked and regulated by a variety of pollutants that mimic estrogen. Ray Peat points out that receptors have been proposed for everything in biology to bring order to complexity and an attempt to limit biology to lock and key mechanisms. Receptors do exist but they don’t explain all the processes that occur.

Progesterone is protective across many aspects of function

There are many studies on progesterone and its broad actions on fertility, blood sugar, sleep, mood and more. Katherina Dalton who produced over one hundred and fifty publications on the role of progesterone and showed that issues such as post-natal depression and morning sickness often resolved with additional progesterone  Dr Dalton even helped individuals in court whose aggressive actions were mediated by progesterone deficiency (Dalton, 1980). Many people often state that we’ve moved on from old medicine but in reality we have moved away from medicine that doesn’t make vast profits for companies. It wouldn’t be unscrupulous to suggest that the blurred lines have been purposeful to confuse both clinicians and the public alike. Don’t just take my word for it, there’s plenty of data to review . In a systematic review of thirteen studies of progesterone by Spark and Willis (Spark & Willis, 2012) they state:

 

‘ Even though the words progestogen and progesterone are not interchangeable they are often used interchangeably which results in confusion about therapeutic use of progesterone.’

‘ Even though the words progestogen and progesterone are not interchangeable they are often used interchangeably which results in confusion about therapeutic use of progesterone.’

Expanding that large randomised control studies in progesterone have not been undertaken and this might primarily be due to poor profit margins from a natural versus  synthetic compounds. It’s hard not to sound a like a conspiracy theorist but there really is no vast sums of money for large corporations when progesterone is used. Given that it also drastically reduces the need for blood pressure, blood sugar, infertility and menopausal medications it starts to make some sense.

Some old books on progesterone, post natal depression and PMS by Katherina Dalton are worth a read. I picked all mine up for a quid or two a few years back but you can still get them.

https://www.amazon.co.uk/Depression-after-Childbirth-Recognise-2001-05-31/dp/B01JXORBK0/ref=sr_1_1?keywords=katherina+dalton&qid=1560326142&s=gateway&sr=8-1

Ray Peats website has dozens of excellent articles too http://raypeat.com/

 References: 

Dalton, K. (1980). CYCLICAL CRIMINAL ACTS IN PREMENSTRUAL SYNDROME. The Lancet. https://doi.org/10.1016/S0140-6736(80)92286-2

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

Peat, R. (1972). Age Related Oxidative Changes in the Hamster Uterus. University of Oregon.

Peat, R. (1997). From PMS to Menopause: Female Hormones in context.

Rossouw, J. E., Anderson, G. L., Prentice, R. L., LaCroix, A. Z., Kooperberg, C., Stefanick, M. L., … Writing Group for the Women’s Health Initiative Investigators. (2002). Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA.

Spark, M. J., & Willis, J. (2012). Systematic review of progesterone use by midlife and menopausal women. Maturitas. https://doi.org/10.1016/j.maturitas.2012.03.015

 

 

 

Seasonal thyroid fluctuations, biology and mood

 As you may have read from previous blogs, the thyroid, its pituitary stimulator - thyroid stimulating hormone (TSH) and the other thyroid hormones are heavily influenced by environment, nutrition and stress. Additionally these hormones can present as normal when relied upon purely by biochemical analysis from the blood. The seasons, differing temperatures, light exposure and effects of hibernation hormones and neurotransmitters can also be a key factor in the expression of adequate energy, organisation and coherence of an individual’s biology. We get sick more so in winter when our function is suppressed and the immune system is called upon to mount a response.

Tromp.png

S.W. Tromp Biometerology 1967.

“ The yearly influenza peak in the Netherlands, around February. Which may be related to the usually low humidity and wind-speed in this period, but which effect is probably accelerated by the decreased thermoregulation efficiency of the body as a result of the preceding cold months and the accompanying changes in the physico-chemical state of the blood such as y-globulin level.”

 Ambient temperature can have a significant effect on TSH production in as much as a colder environment increases TSH and warmer temperatures decrease TSH production and thyroid requirement. Observations have suggested a biphasic seasonal nature of TSH secretion, with increased TSH readings during winter time suggesting what could be a functionally hypothyroid or subclinical hypothyroidism which resolved during the summer months (Kim et al., 2013). As this stress increases throughout longer days of darkness, organisational hormones decrease, whilst stress hormones increase. If chronic enough, or in an unstable biology, stress can decrease the accuracy of TSH to predict a low thyroid state

 Light, both red and ultraviolet (UV) are well-known modulators of immune function, metabolism and mitochondrial production of energy or  adenosine triphosphate (ATP) (Wong-Riley et al., 2005) (Karu, 2010). These aspects of sunlight, exert their influence via enhancement of aerobic metabolism (at cytochrome c) and immunity enhancing via infra-red (NIR) and vitamin D synthesized by UV respectively.  The variation in light exposure as a consequence of daily sleep, darkness and seasonal variations present relationships that may explain the secretory patterns of TSH in healthy subjects. More than 100 years ago, thyroid function could be suggestively viewed via uptake of thyroid iodine levels in seasonal variations. (Fenger and Siedell 1913). Thyroid iodine levels rose during the summer in sheep, pigs and cows and decreased during the winter reflecting the variations in the need for TSH/TH production in healthy organisms. 

Seasons, Thyroid and Mood

 Depression is a known symptom of hypothyroidism and some studies have highlighted the need for a lower TSH value in the presence of depressive symptoms (Talaei, Rafee, Rafei, & Chehrei, 2017) (Hage & Azar, 2012). The former authors suggest a cut-off value of 2.5 mU/L for TSH as a point for treating hypothyroidism, which highlights the need for assessing symptoms as part of an effective strategy for diagnosing hypothyroidism. This compares to the attitude taken to expecting mothers where values should be decreased to compensate for hypothyroid states but in reality should be applied across the board.

 Relationships concerning seasonal variations of mood are well documented and decreased Beck mood scores are associated with the shorter days of winter (Harmatz et al., 2000). Seasonal affective disorder (SAD) may be a reflection of the increase in serotonin and melatonin and depression of thyroid hormone, which are increased by shorter days and in mammals are associated with hibernation. This aspect seems to be lost on those treating transient depressed states but light therapy does appear to be taken seriously these days. I would encourage anyone wanting more information on serotonin and mood to check out the extremely well written blog Against Utopia.

 As days become shorter and light exposure is decreased, influencing cellular function and metabolism negatively. The extended effects of melatonin from the shorter days can antagonise TSH secretion via its inhibitory action on TH, increasing prevalence throughout winter. Whilst fluctuations in TSH levels in response to seasonal changes are well-known to occur, these fluctuations are also under the influence of the nutritional and environmental factors that can suppress TSH values.

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Wake me up when it’s spring?

Violent suicides increase with the onset of spring from March to May. I was trying to think why this might occur? After speaking to a friend recently about depression, they said that holding onto the feelings of a blanketed, safe, dark environment by being it home (in a somewhat hibernation like state), and gorging on boxsets or podcasts was easy to do and a comfort. I wonder if the shorter phases of darkness and increased light remove that blanket of increased serotonin and melatonin and the light itself might become a stressor that takes away that comfort? Those most at risk might explain this seasonal increase in suicides?

Ray Peat (1997) has discussed various aspects of stressors such as darkness, oestrogen-cold sensitive enzymes and nutritional factors affecting endocrine systems, adding an interesting perspective on hormone production and relationships with temperature changes (Peat, R. and Soderwall, 1972) (Peat, 1997)(Peat, 1972).

In states of undetectable SCH mediated by the stress, a hypothermic state may stimulate the adrenal stress system to compensate for a low-metabolic and decreased temperature state.  Activated compensatory stress response pathways may explain poorly detected hypothyroid patients. Decreased metabolic rate, lowered temperature and pulse rate are well-known signs of hypothyroidism. β adrenergic mechanisms involving increased catecholamine production such as adrenaline and noradrenaline (NA) can increase Tb and RHR. In my previous blog on body temperature, I explained how low temperature can be indicative of low thyroid function when blood tests appear normal.

  

References:

Hage, M. P., & Azar, S. T. (2012). The link between thyroid function and depression. Journal of Thyroid Research. http://doi.org/10.1155/2012/590648

Harmatz, M. G., Well, A. D., Overtree, C. E., Kawamura, K. Y., Rosal, M., & Ockene, I. S. (2000). Seasonal variation of depression and other moods: A longitudinal approach. Journal of Biological Rhythms. http://doi.org/10.1177/074873000129001350

Karu, T. I. (2010). Multiple roles of cytochrome c oxidase in mammalian cells under action of red and IR-A radiation. IUBMB Life. http://doi.org/10.1002/iub.359

Kim, T. H., Kim, K. W., Ahn, H. Y., Choi, H. S., Won, H., Choi, Y., … Park, Y. J. (2013). Effect of seasonal changes on the transition between subclinical hypothyroid and euthyroid status. Journal of Clinical Endocrinology and Metabolism. http://doi.org/10.1210/jc.2013-1607

Peat, R. and Soderwall, A. L. (1972). Estrogen stimulated pathway changes and cold -nactivated enzymes. Physiol Chem Phys, 4((3)), 295–300.

Peat, R. (1997). From PMS to Menopause: Female Hormones in context.

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

S.W., Tromp. (1967). Biometeorology, iia and b. Symp. Publ. Div. Pergamon Press (Oxford).

Talaei, A., Rafee, N., Rafei, F., & Chehrei, A. (2017). TSH cut off point based on depression in hypothyroid patients. BMC Psychiatry, 17(1). http://doi.org/10.1186/s12888-017-1478-9

The Armour Laboratories. (1945). The Thyroid Gland and Clinical Application of Medicinal Thyroid. Armour Laboratories.

Wong-Riley, M. T. T., Liang, H. L., Eells, J. T., Chance, B., Henry, M. M., Buchmann, E., … Whelan, H. T. (2005). Photobiomodulation directly benefits primary neurons functionally inactivated by toxins: Role of cytochrome c oxidase. Journal of Biological Chemistry. http://doi.org/10.1074/jbc.M409650200

 

Body temperature and health

Most people are so confused as to what constitutes good health these days and when they turn up to my office in low metabolic states with digestion, sleep, energy, mood and other issues. One of the first things that they say is that they eat really healthily. If you throw into the melting pot the obsession with the keto diet, chronic calorific restriction (CR) or other modalities, those short term gains have turned into long term deficits. I’ve long opined that health in general terms can be defined by:

 

·      Good energy

·      Good Digestion 2-3 bowel movements per day

·      Restorative sleep

·      Balanced mood free of depression or anxiety

·      Desire for life, motivation, hobbies and interests

·      Healthy libido

·      Absence of pain

Humans are endotherms that regulate their temperature at 37 degrees centigrade.jpg

What does your body temperature suggest about your health?

Get cold…read on

I’ll also add to that list a warm body and the ability to generate efficient energy,  a phrase biologists might use is a state of negative entropy. Entropy is a state associated with decay and disorder and as entropy increases, equilibrium is achieved - where a state of no energy in and no energy out or death of a living system occurs. The basis for life and metabolism is governed by the enzymes. Enzymes function well in an appropriate temperature and in a medium that is neither too acidic nor too alkaline. Mammals and specifically humans are endotherms that regulate their temperature in  tight range at approximately 37 degrees Centigrade (C) or 98.6 Fahrenheit (Bicego, Barros, & Branco, 2007). The central compartment theory of temperature  suggests that the head and the core should maintain a relatively stable temperature, due to the rich vascular supply and that the periphery may vary some 2-4 C.  

In a recent study that I conducted I suggested that the peripheral and core temperatures should remain at a similar level of about 37 C . The suggestion that a decreased body temperature recorded in the head, might be the last place that you would see a reduction due to the large quantities of glucose that the brain uses to maintain function. It’s possible to suggest that the slowing of function in low energy and hypothyroid states might be observed initially in the trunk or core. The well documented symptoms of constipation, decreased heart rate, slowed contraction relaxation of the heart and arteries and reduced peripheral relaxation of tendons (Achilles tendon reflex) might appear in the trunk and peripherally due to the preferential oxidation of glucose initially. Due to the vast systemic implications of low thyroid function, many different paths of decreased function might occur, dependant on nutrition, environmental stimulus and other stressors. In my study I didn’t find this but what I did find is strong linear correlations between low body temperature in both the mouth and armpit, multiple low thyroid symptoms (mean 6.8 per subject) and yet normal blood values.

Humans are endotherms that regulate their temperature at 37 degrees centigrade-2.jpg

Thyroid hormone affects all aspects of biology

 

There are many factors that can decrease body temperature such as CR, fasting, estrogen, stress, pollution, over exercise and more. CR has been suggested as a mechanism for maintaining longevity but studies lack any conclusive evidence (Carrillo & Flouris, 2011) and a theory that a cold body, decreases metabolism, oxidation and damage therefore preserving tissues. Another emergent theory and results show in rodent studies, that mammals with a high energy intake, high metabolism and organised biology can increase life span (John R. Speakman et al., 2004) (J. R. Speakman, 2005). Think about this for a minute:

Calorific restriction makes the body cold, decreases metabolic rate  (via inhibition of thyroid hormone) and disorganisation of tissues. Entropy State

Adequate energy, maintains body temperature and organises tissues to function at their best. Negative entropy state.

From an evolutionary perspective fasting due to lack of food was a necessity. Fasting these days could be a useful tool, if you were prone to constant overeating but if your system lacks the flexibility to do so problems can occur. That’s not to say that calorie restriction for weight loss isn’t helpful but sustained CR in a system that doesn’t respond well might be counterproductive. Pollution has increased at a phenomenal rate clearly affecting physiology and hormones (Gore et al., 2015). Does it make sense that a so called detox diet, low in calories, protein, carbohydrates can enhance the function of detoxification, when liver function is energy and thyroid dependant? Skipping breakfast alone in some is associated with increased cortisol, glucagon and metabolic inflexibility (Jakubowicz, Wainstein, Ahren, et al., 2015) (Jakubowicz, Wainstein, Ahrén, et al., 2015). These factors can also decrease the mitochondrial uncoupling proteins which are responsible for increased body temperature.

Ageing is also associated with decreased metabolic rate, colder bodies and accepted increases in thyroid hormone stimulating values (TSH) (Laurberg, Andersen, Pedersen, & Carlé, 2005) . If symptoms of failing biology are present with isolated thyroid symptoms such as increased cholesterol,  , high blood pressure and sugar, cardiovascular issues and even cancer the acceptance of TSH and other thyroid hormone analysis to accurately predict hypothyroidism should be considered. Body temperature and metabolic rate was reliably used in the last century to diagnose hypothyroidism with qualitative analysis of symptoms and symptoms resolved with thyroid hormone treatment (Barnes, 1942) (McGavack, Lange, & Schwimmer, 1945) (Peat, 1999). Whilst thyroid is useful for restoring function, food and other factors can be used to restore and maintain function (previous blog on maintaining the aerobic system)

Certain nuances exist in temperature regulation that are dependant on acute or chronic exposure to stressors and a slowing down of the system through  a functionally, subclinical or overt hypothyroid state. In short term fasting, TSH is initially raised then decreases, negating thyroid blood tests. In the same manner the time frame of any stressor can dictate whether short or long term compensations of  the sympathetic adrenergic system is supporting the system. In well established feedback mechanism it’s known that as TSH increases so does cortisol and as body temperature approaches hypothermic levels (around 35C) cortisol, adrenaline and noradrenaline can increase body temperature as a protective response.

In a world where excess environmental and social stressors are ever increasing - it might make sense to maintain an efficient, organised warm body rather than reducing its function and heat.

 

References:

 

Barnes, B. (1942). Basal temperature versus basal metabolism. Journal of the American Medical Association, 119(14), 1072–1074. http://doi.org/10.1001/jama.1942.02830310006003

Bicego, K. C., Barros, R. C. H., & Branco, L. G. S. (2007). Physiology of temperature regulation: Comparative aspects. Comparative Biochemistry and Physiology - A Molecular and Integrative Physiology. http://doi.org/10.1016/j.cbpa.2006.06.032

Carrillo, A. E., & Flouris, A. D. (2011). Caloric restriction and longevity: Effects of reduced body temperature. Ageing Research Reviews. http://doi.org/10.1016/j.arr.2010.10.001

Gore, A. C., Chappell, V. A., Fenton, S. E., Flaws, J. A., Nadal, A., Prins, G. S., … Zoeller, R. T. (2015). Executive Summary to EDC-2: The Endocrine Society’s second Scientific Statement on endocrine-disrupting chemicals. Endocrine Reviews. http://doi.org/10.1210/er.2015-1093

Jakubowicz, D., Wainstein, J., Ahrén, B., Bar-Dayan, Y., Landau, Z., Rabinovitz, H. R., & Froy, O. (2015). High-energy breakfast with low-energy dinner decreases overall daily hyperglycaemia in type 2 diabetic patients: a randomised clinical trial. Diabetologia, 58(5), 912–919. http://doi.org/10.1007/s00125-015-3524-9

Jakubowicz, D., Wainstein, J., Ahren, B., Landau, Z., Bar-Dayan, Y., & Froy, O. (2015). Fasting until noon triggers increased postprandial hyperglycemia and impaired insulin response after lunch and dinner in individuals with type 2 Diabetes: A randomized clinical trial. Diabetes Care, 38(10), 1820–1826. http://doi.org/10.2337/dc15-0761

Laurberg, P., Andersen, S., Pedersen, I. B., & Carlé, A. (2005). Hypothyroidism in the elderly: Pathophysiology, diagnosis and treatment. Drugs and Aging. http://doi.org/10.2165/00002512-200522010-00002

McGavack, T. H., Lange, K., & Schwimmer, D. (1945). Management of the myxedematous patient with symptoms of cardiovascular disease. American Heart Journal. http://doi.org/10.1016/0002-8703(45)90476-5

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

Speakman, J. R. (2005). Body size, energy metabolism and lifespan. Journal of Experimental Biology. http://doi.org/10.1242/jeb.01556

Speakman, J. R., Talbot, D. A., Selman, C., Snart, S., McLaren, J. S., Redman, P., … Brand, M. D. (2004). Uncoupled and surviving: Individual mice with high metabolism have greater mitochondrial uncoupling and live longer. Aging Cell. http://doi.org/10.1111/j.1474-9728.2004.00097.x