Better gut health with less bacteria?

Can you have better gut health with less bacteria? There’s an old saying in the integrative health world that ‘ Death begins in the colon.’ These were the words of the 1906 Nobel science award holder Elie Metchnikoff, a Russian scientist who did much to elaborate on the mechanisms of embryology, immunology and other aspects of health and disease. These days there’s much that has been written about the micro biome and the suggestion that diverse microbes within the bowel are an important factor in health. How we need to eat plenty of fibrous and fermented foods for better health. But how true is this and are more bacteria necessary for better digestion and longer life? “The retention of faecal matter for several days very often brings harmful consequences. Organisms which are in a feeble state from some cause are specially susceptible to damage of the kind referred to.” (Metchnikoff & Metchnikoff, 1908)

Ok so you aren’t likely to die anytime soon from being constipated for several days, you might feel like crap (excuse the pun). But what if the repetition of constipation is over years? We have seen that hypothyroidism and constipation is clearly linked and can induce small intestinal bacterial overgrowth (Lauritano et al., 2007). An inability to remove the waste products is a particular burden on a stressed system.

"Not only is there autointoxication from the microbial poisons absorbed in, cases of constipation but microbes themselves may pass through the walls of the intestines."

This description of endotoxin and other bacterial end products damaging and permeating the intestinal wall is a well-known modern concept of leaky gut or intestinal hyper permeability. Metchnikoff’s describes the putrefaction (think fermenting mass of stinky stuff) of foods within the bowel that lead to the damage described in a permeable gut lining that allows bacteria and endotoxin into the blood stream.

There’s a theory that I have, as it’s clear that not all people have constipation. Many present with irritable bowel syndrome (IBS) like states, loose and perhaps a product of irritation induce by high serotonin and histamine (which by keeping to a minimum can also improve sleep and mood). It’s plausible to suggest that some people have already gone through a constipated phase induced by either a low energy or thyroid state, which may give way to a high adrenaline state over time. The lack of movement in the bowel for some can set the scene for future IBS reactions due to the accumulative damage induced by constipation, putrefaction, bacterial end products and increased irritation. Some clients have noticed that they previously went through a constipated phase before they arrived at their suggested IBS.

So if the current theme of recommending probiotics, raw and fermented foods is in vogue. What does that mean for the digestive system. I remember a newsletter from Ray Peat suggesting that animals born in a sterile environment generally live longer and have a higher metabolic rate. This in itself is a hard, near impossible feat to achieve outside of a sterile laboratory but consider this - Most babies are grown within a womb that does not contain any bacteria, as soon as they come through the birth canal and into the world at large. The bacterial management of life comes into play and had it come any sooner, may have had disastrous consequences. Other observations of Metchnikoff related to the longevity of birds, which have a high metabolic rate and limited intestinal flora -

‘Even in birds of pray which feed upon putrid flesh, the number of microbes in the intestine is remarkably limited. I have investigated the case of ravens which I fed flesh which was putrid and swarming with microbes. The droppings contained very few bacteria, and it was remarkable that the intestines had not the slightest smell of putrefaction. Although the opened body of a herbivorous mammal, such as a rabbit, gives off a strong smell of putrefaction, the body of a raven with its digestive tube exposed has no unpleasant smell. The absence of putrefaction in the intestine is probably the reason of the great longevity of such birds as parrots, ravens, and their allies.’

Metchnikoff also states that despite the absence of bacteria, their organisation and metabolism may be the primary driver for long health. Therefore if we were to keep bacterial interference at bay might we be better at living longer lives by improving our gut health? Our metabolism and cellular health is the key to prevention of many disease states. Extra bacteria may just be another factor that our immune system has to contend with and may be at the heart of autoimmune issues. From a comparative biology standpoint many other herbivorous animals don’t live as long as omnivorous animals. Horses, cows, and sheep live very short lives in comparison to other mammals that eat a wide range of foods. The main exception being the elephant, which has an extremely large intestine like other vertebrates.

Probiotics and fermented foods provide a mixed bag of research(Goldenberg et al., 2015). In many studies bacterial infections and digestive issues have not been resolved by probiotics. They do seem to be particularly effective at reducing bacterial/food poisoning cases and decreasing the diarrhoea like state by a day or two. Primarily this acts as a competing organism in the battle of the bowel and maybe why faecal implants have been shown to beneficial in the short term for some.. Even beneficial strains of bacteria such as lactobacillus can be problematic in excess due to the high levels of lactic acid leading to d-lactate acidosis, decreasing our gut health and overall wellbeing.

After all increased bacteria equals increased immune system responses and constant battles, for some there’s only so much that a faltering metabolism and immune system that one can take. Providing easily digested nutrients that limit bacterial growth and metabolites, that doesn’t burden a compromised digestive system seems prudent. In hypothyroidism gastric secretions such as hydrochloric acid are often lowered, further compromising digestion. Easily digested nutrients equals easily available source of energy and macronutrients.

To read more on how to combat these issues, to improve your gut health, digestion, mood and energy, this article is extended in the members’ area or there's also some information in this blog from 2017.

References:

Goldenberg, J. Z., Lytvyn, L., Steurich, J., Parkin, P., Mahant, S., & Johnston, B. C. (2015). Cochrane Database of Systematic Reviews. The Cochrane database of systematic reviews (Vol. 12). http://doi.org/10.1002/14651858.CD004827.pub4

Lauritano, E. C., Bilotta, A. L., Gabrielli, M., Scarpellini, E., Lupascu, A., Laginestra, A., … Gasbarrini, A. (2007). Association between hypothyroidism and small intestinal bacterial overgrowth. The Journal of Clinical Endocrinology and Metabolism, 92(11), 4180–4184. http://doi.org/10.1210/jc.2007-0606

Metchnikoff, E., & Metchnikoff, I. I. (1908). The Prolongation of Life: Optimistic Studies. Our post human future. Consequences of the biotechnology revolution. Retrieved from http://books.google.com/books?hl=en&lr=&id=U8bgKGvZJV0C&pgis=1

How to keep your energy chain maintained. Protective compounds.

How to keep your (electron transport) chain-2.png

How to keep your energy chain ( electron transport or ETC) running might not be something you think about, but if you are concerned about being healthier, this is an often overlooked area of maintaining health. It came as a huge disappointment to find out that the historical use of a false tooth compartment to hide cyanide tablets (for soldiers and spies) to commit suicide was pure fantasy. Although cyanide hidden in glasses appears to be more likely, the role of cyanide to induce rapid death is indisputable. We are at a time where industrial pollutants are at an all time high and cyanide being one of those pollutants, might not induce a theatrical foaming of the lips and contorted last throws of life (as seen in many an old war movie); it may induce a slower, less dramatic affect on cell function and efficient biology over time.

Cyanide is certainly ubiquitous in the industrialised environment but unknowingly for many, trying to achieve a ‘healthier’ balanced diet, cyanides are present in many foods favoured by the health conscious.

There are more than 2500 plants associated with cyanide content, these include almonds, millet, lima beans, soy, spinach, bamboo shoots, and cassava roots (which are a major source of food in tropical countries), cyanides occur naturally as part of sugars or other natural compounds. Cassava consumption (especially so in poorer countries) is associated with the neurological, irreversible disease called Konzo (Nzwalo & Cliff, 2011). Some other major sources of cyanide are:

Seeds/kernels of apples, apricots, plums, peach and nectarine, millet, almonds, flax seed, , spinach, sorghum gluten free flour like cassava often used to replace normal flours. Simply type in cassava poisoning into a search engine and you'll see some cases where dozens of people from the same meal have died from a so called bad cassava. Most likely it was the poor preparation and failure to remove the cyanide from the cassava that lead to these numerous deaths. In one case in the Philippines in 2005, 27 children died in such a manner.

Other cyanide sources include vehicle exhaust, releases from chemical industries, burning of municipal waste, and use of cyanide-containing pesticides (Jaszczak et al 2017) and the more obvious smoking.

Excess cyanide (ions) is able to disrupt the efficient production of energy that is produced through the electron transport chain/mitochondria (energy producing cells) where water, carbon dioxide and energy are end products. The loss of this function often creates a decreased ability to utilise carbohydrate effectively and the result can be an excess of lactate, which diminishes cell function further and creates hypoxia. Lactic acid seems to be getting some praise of late but it is the hallmark of inefficient energy production, as observed in the so called Warburg state seen in cancer (5). As cyanide levels increase cellular death occurs through increased lactic acidosis. This is the death throw that you see our actors who have crunched down on that mythical hydrogen cyanide capsule. It's also observed as a cause of death to the unlucky Private Santiago in A Few Good Men, where he has a rag with cleaning fluid, stuffed into his mouth creating a not to dissimilar occurrence.

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You want the truth? You can't handle the truth but it might be that a combination of dietary cyanide and pollutants might not be as healthy as you think.

If there’s a ubiquitous source of cyanide and other pollutants in the environment does it make sense to have plenty of cyanide containing foods? Let’s not take this out of context. Here and there - having foods that have some levels of cyanide in should pose no problem to a healthy individual but what if your diet contains a regular supply and also contains plenty of vegetables that contain goitregens or foods that slow down thyroid function (and also contain cyanide) it may be problematic. Many people seem to promote a diet high in raw green vegetables, nuts, seeds, often low in adequate protein and often deficient in adequate energy/carbohydrate. In this instance the so-called healthy diet, in a highly polluted area becomes a burden not a provider of energy to promote optimal thyroid health, energy and liver enhancer (energy, detox, hormones etc.).

Chris Masterjohn’s report - Thyroid toxins, highlights the out of context suggestions of nutritional science evaluation of compounds in a test tube compared to a real world scenario.

The line that divides nutrients from toxins is often thin and equivocal. Since any given chemical may react in any number of ways in a test tube depending on the other chemicals with which it is combined, it is often possible to prove such a chemical to be both a nutrient and a toxin.

If a diet is to be considered healthy, it should meet the body’s energetic demands without reducing its function. A healthy energy chain ensures that carbohydrate is metabolised efficiently without an excess of lactic acid production.

The abundance of glucosinolates found in broccoli, cauliflower (and other brassica vegetables) and other cyanide like food sources combined with other environmental pollutants may pose substantial problems over time. Heavy metals like mercury, which are also increasing environmentally can decrease selenium and iodine uptake creating another algorithm for decreased function.

 cell enhancers

cell enhancers

Caffeine can be considered a useful compound for preventing excess uptake of metals and may go someway to explain the anti-oxidant and other positive effects observed in neurological degeneration diseases such as Alzheimer’s and dementia (Liu et al., 2016). Other compounds like methylene blue can be seen in the next diagram that promote a better energy chain.

" As I have shown in my earlier days , one can knock out the whole respiratory chain by cyanide and then restore oxygen uptake by adding methylene blue  which takes the whole electron transport chain over between dehydrogenases and  O2 ."   Albert Szent Györgi

You can also reduce the risk of excess cyanides in foods through heating, boiling and other forms of processing but given that the zeitgeist is as raw, wholesome and as gluten free as one can be, it’s unlikely that this occurs in the upwardly mobile food neurotic.

References:

  1. Jaszczak, E., Polkowska, Ż., Narkowicz, S., & Namieśnik, J. (2017). Cyanides in the environment—analysis—problems and challenges. Environmental Science and Pollution Research, 24(19), 15929–15948. http://doi.org/10.1007/s11356-017-9081-7

  2. Liu, Q.-P., Wu, Y.-F., Cheng, H.-Y., Xia, T., Ding, H., Wang, H., … Xu, Y. (2016). Habitual coffee consumption and risk of cognitive decline/dementia: A systematic review and meta-analysis of prospective cohort studies. Nutrition, 32(6), 628–636. http://doi.org/10.1016/j.nut.2015.11.015

  3. Nzwalo, H., & Cliff, J. (2011). Konzo: From poverty, cassava, and cyanogen intake to toxico-nutritional neurological disease. PLoS Neglected Tropical Diseases. http://doi.org/10.1371/journal.pntd.0001051

  4. Masterjohn, C. Thyroid Toxins Report. 2007

  5. http://raypeat.com/articles/articles/cancer-disorder-energy.shtml

  6. Szent Györgi, A. Introduction to a Submolecular Biology. Academic Press. 1960.

http://www.keithlittlewoodcoaching.com

A biochemical approach to decreasing muscle pain with food and hormones.

 pain and hormones

pain and hormones

A biochemical approach to decreasing muscle pain is often the last place most people look and that includes many pain specialists. Modulating pain and hormones through food and other variables can create some impressive results. Aches and pains are a common theme in every day living. Some people seek to push themselves harder with excessive training schedules, others spend more time in a seated position and other factors contribute to tissue not responding the way that it should. Pain and the concept of nociception is a system of feedback for the body that is protective in essence. You touch something you shouldn’t; first pain kicks in to remove you from the painful stimulus (lasts less than 0.1 seconds), after that and depending on severity of damage second pain kicks in.

First pain and second pain (both reside in the anterolateral system or ALS) utilise different chemical messengers and another factor for this form of feedback is that other nociceptive factors like touch, visual, auditory and other sensations of stress can be part of the problematic feedback if not resolved. All of these have the capacity to interrupt optimal motor control and functioning of joints and soft tissues and affect hormone profiles. Even a bad smell can create neurological chaos.

Another less well known aspect (in therapy based settings) of disruptive function in muscle tissue are the effects of hormones that may lead to decreased feed back and be responsible for pain. Hypothyroidism affects muscle tissue via energy and neurological deficiencies.

Hypothyroidism results in

Slower peripheral and central nerve conduction velocity Lower body temperature is a factor creating slowed velocity Decreased active cell transport in the cerebral cortex Decreased flux of sodium and calcium for contraction/relaxation Poor production of energy for contraction/relaxation Decreases depolarisation of action potential

 cold body

cold body

In a nutshell a colder, slower body leads to a decreased   coordinated body that has a hard time contracting and relaxing muscle tissue. This can lead to increased incidence of injury and pain.

A slowed heart rate is a sign of hypothyroidism and the bradychardia (slowed heart rate) should serve the purpose of describing the decreased rate of function throughout all muscle tissue. Thyroid hormone can improve both rate of contraction and relaxation in both fast and slow twitch muscles but also exerts a cardio protective role on blood vessels and bowel function via smooth muscle tissue. The documented symptoms of hypertension and constipation along with the neuromuscular actions tend to resolve with adequate thyroid hormone (Gao, Zhang, Zhang, Yang, & Chen, 2013).

Prior to initiating thyroid therapy it’s essential to rule out functionally hypothyroid states induced by diet, stress, excess exercise and other environmental factors. Many clients often present with lowered temperature, with cold hands, feet and nose, altered bowel, sleep and emotional function, which can often be resolved with appropriate energy and decreased intestinal irritants.

Chronic pain increases cortisol production which decreases thyroid hormone production (Samuels & McDaniel, 1997) as does fasting or calorie restriction which induces a decrease in available T3 (thyroid hormone) (Hulbert, 2000).

This gives us two approaches 1) to reduce pain with appropriate therapy and to ensure that adequate energy modulates the suppression of excess cortisol and increases available thyroid for tissue organisation and recovery.

Hormones also affect tendons; diabetics and poor insulin profiles appear to create disorganised tendon structure but this may be a factor related to decreased available thyroid hormone. Hypothyroidism decreases available T3 within tendons, which can decrease growth, structure, and collagen production and create hypoxia of tissue leading to calcification.

Estrogen, although necessary for growth of tissue can often be found in excess creating problematic growth. Estrogen is also well known to decrease thyroid hormone and can provide an explanation why more females then men tend to be hypothyroid. The decrease in both thyroid hormone and progesterone can increase muccopolysacharides, which increase pressure in tissues, creating puffy, oedema like states. The swelling can be linked to many pain states which include carpal tunnel, which can be resolved with progesterone and thyroid in the absence of physical therapy. Progesterone also appears to induce myelination of nerves (surrounds and allows nerve conduction) and decreases inflammation (Milani et al 2010).

Energy production remains  a most potent form of therapy for decreasing pain, optimising rehabilitation and restoring tissue function.

References:

  1. Gao, N., Zhang, W., Zhang, Y., Yang, Q., & Chen, S. (2013). Carotid intima-media thickness in patients with subclinical hypothyroidism: A meta-analysis. Atherosclerosis, 227(1), 18–25. http://doi.org/10.1016/j.atherosclerosis.2012.10.070

  2. Hulbert, A. (2000). Thyroid hormones and their effects: a new perspective. Biological Reviews of the Cambridge Philosophical Society, 75(4), 519–631. http://doi.org/10.1017/S146479310000556X

  3. Milani, P., Mondelli, M., Ginanneschi, F., Mazzocchio, R., & Rossi, A. (2010). Progesterone - new therapy in mild carpal tunnel syndrome? Study design of a randomized clinical trial for local therapy. Journal of Brachial Plexus and Peripheral Nerve Injury, 5(1). http://doi.org/10.1186/1749-7221-5-11

  4. http://raypeat.com/articles/aging/aging-estrogen-progesterone.shtml

  5. Samuels, M. H., & McDaniel, P. A. (1997). Thyrotropin levels during hydrocortisone infusions that mimic fasting- induced cortisol elevations: A clinical research center study. Journal of Clinical Endocrinology and Metabolism, 82(11), 3700–3704. http://doi.org/10.1210/jcem.82.11.4376

Poly Cystic Ovary Syndrome (PCOS) - inheritance, environment and stress.

Estrogen excess.png

Poly Cystic Ovary Syndrome - inheritance, environment and stress. Recently I took on a client who was diagnosed with polycystic ovary syndrome (PCOS), a slightly wayward insulin profile and the ‘best practice’ of oral contraceptives and Glucophage (metformin- blood sugar regulating drug) were suggested. My client had started bleeding daily and was informed that this was normal for three months but would help out with PCOS and weight gain. However this seemed at odds with my current knowledge and experience of biology and endocrinology. There are plenty of studies highlighting the diabetes inducing effects of estrogen and oral contraceptives.

Glycemia constitutes a fundamental homeostatic variable, and hence its alteration can lead to a number of pathophysiological conditions affecting the internal milieu of the human being. Since the early 1960s, the intake of oral contraceptives has been associated with an increased risk of developing disorders of glucose metabolism.(Cortés & Alfaro, 2014)

Is best practice the efforts of a global network of doctors or simply a corporate led strategy? Don’t get me wrong; the world is full of competent, passionate and well-meaning doctors who signed up to help others. But the concept of both best practice and clinical governance seem a utopian ideal when those that are responsible for drug development are companies whose primary function is to make as much money as possible, without appropriate direction.

Joseph Dumitt in his book Drugs for Life (2012) highlights that there hasn’t been a scientist at the head of a pharmaceutical company for many years and their direction being driven by economists and marketers. As there are many examples of absolutist statements regarding drugs and their positive effects on health that lack congruence over time, you’ll forgive me for sounding like a conspiracy theorist. How about hormone replacement therapy (HRT) for better health despite its negative outcomes related to cardiovascular events or cancer? Or statin therapy for decreasing unnecessary risk factors based upon skewed data and early terminated trails with no public access to trial data (Lorgeril & Rabaeus, 2016)?

Back to PCOS. I have written previously about the effects of metformin and its use in gestational diabetes, and the problems it poses trans-generationally. It’s possible to suggest that the failure to act with appropriate biological interventions perpetuates the cycle of acquired traits from parents that are passed to offspring, treated ineffectively and generations of reproductive (and other tissues) tissue conditions continue without being resolved.

The biologist Jean Baptiste Lamarck's fourth law stated:

“ Everything which has been acquired..or changed in the organisation of an individual during its lifetime is preserved in the reproductive process and is transmitted to the next generation by those who experienced the alterations. “

It's worth pointing out that this is not isolated to the female of the species as the factors below have been shown to be instrumental in reproductive issues (testicular dysgenesis, hypospadias etc) in males.

The environment has been shown to be instrumental in the development of reproductive tissue disorders, diabetes and cancer but more emphasis is placed on the individual and their food choices rather than acknowledgement of industrial responsibility. Positive associations between levels of polychlorinated bisphenyls (PCBs), pesticides, polycyclic aromatic hydrocarbons (PAHs) and dichlorodiphenyldichloroethylene (DDE) have been confirmed in multivariate data analysis (Yang et al., 2015). Relationships between increases of luteinising hormone (LH) PCO, hyperandrogenism, annovulation, insulin resistance and pollutants are significant and may add to issues of detection, due to the subtle long term perturbations that often affect endocrine function. Stress, other pollutants and medications contribute to further problems that burden not only reproductive tissue but also other organizational hormones such as thyroid hormone.

PCOS is defined medically by the following: One of the main problems of treating PCOS with contraception is the many studies that clearly show a relationship between estrogen and decreased insulin sensitivity (Godsland et al., 1992)(Cortés & Alfaro, 2014). Progestin’s, the synthetic version of progesterone, also pose many problems but this has not deterred the inclusion of estrogen and progestin contraceptives as another inappropriate form of treatment. The burden of estrogen induced by the sources suggested above comes at a cost and it’s well known that an excess of estrogen can suppress thyroid function (thyroid is necessary for detoxification of estrogen and another organisational hormone progesterone.

Both thyroid and progesterone are known to improve insulin sensitivity and can create beneficial changes to disorganised tissue induced by an excess of estrogen. Thyroid nodules and uterine fibroids appear to be intimately linked by an excess of estrogen (Kim et al., 2010) and suppression of thyroid tumours can be achieved by thyroid stimulating hormone (TSH) suppression by thyroxin supplementation (Grussendorf, Reiners, Paschke, & Wegscheider, 2011). An old rambling on thyroid nodules and fibroids.


Breaking the cycle requires interventions that address inheritance, environment and individual stressors. Strategies that involve adequate nutrition that build biology not reduce it, use of protective compounds like progesterone, thyroid and adequate carbohydrate can be of great benefit. Although this stands in contrast to the best practice of contraception, blood sugar medication and poorly thought out nutritional advice of restricting carbohydrates. As the environment appears to drive most of the increasing numbers of issues like PCOS, it becomes important to increase robustness, restrict exposure to what we can control and become more adaptable to what we can’t.

To find out more about coaching for these issues.

References:

Burkhardt, R. W. (2013). Lamarck, evolution, and the inheritance of acquired characters. Genetics, 194(4), 793–805. http://doi.org/10.1534/genetics.113.151852

Cortés, M. E., & Alfaro, A. a. (2014). The effects of hormonal contraceptives on glycemic regulation. The Linacre Quarterly, 81(3), 209–218. http://doi.org/10.1179/2050854914Y.0000000023

Dumit, J. (2012). Drugs for Life. Duke University Press.

Godsland, I. F., Walton, C., Felton, C., Proudler, A., Patel, A., & Wynn, V. (1992). Insulin resistance, secretion, and metabolism in users of oral contraceptives. Journal of Clinical Endocrinology and Metabolism, 74(1), 64–70. http://doi.org/10.1210/jcem.74.1.1530790

Grussendorf, M., Reiners, C., Paschke, R., & Wegscheider, K. (2011). Reduction of thyroid nodule volume by levothyroxine and iodine alone and in combination: A randomized, placebo-controlled trial. Journal of Clinical Endocrinology and Metabolism, 96(9), 2786–2795. http://doi.org/10.1210/jc.2011-0356

Kim, M.-H., Park, Y. R., Lim, D.-J., Yoon, K.-H., Kang, M.-I., Cha, B.-Y., … Son, H.-Y. (2010). The relationship between thyroid nodules and uterine fibroids. Endocrine Journal, 57(7), 615–21. http://doi.org/10.1507/endocrj.K10E-024

Lorgeril, M. De, & Rabaeus, M. (2016). Beyond confusion and controversy, can we evaluate the real efficacy and safety of cholesterol-lowering with statins? Journal of Controversies in Biomedical Research, 1(1), 67. http://doi.org/10.15586/jcbmr.2015.11

Sleep, stress, sugar. Eat sugar for better sleep.

 Onset of sleep

Onset of sleep

Can you improve sleep and decrease stress by eating sugar for better sleep? If you put sleep, stress and sugar in the same sentence, most people think they have already put the three together with something like; too much sugar causes stress and affects your sleep. If you read on you should find yourself advantageously aware of sleep biology and why consuming sugary foods before sleep, and indeed if you wake up are the answer for a deeper nights sleep.

Ah a good nights sleep. You remember one of those don’t you? As a father to 3 children I have had my fair share of sleepless nights but a recent 11 hour sleep whilst my kids slept for 12 hours, recently reminded me of why everyone should strive for better sleep and the common approaches that people tend to fail to implement. A couple of years ago I studied a short course on the neurobiology of sleep with the University of Michigan and I found it useful as it correlated with aspects of serotonin function that Ray Peat (7,8) had talked previously talked about.

Generalisations of sleep biology phases are:

Sleep latency - Getting your sorry arse to sleep

NREM sleep - Keeping your sorry arse asleep

REM sleep - Deep arsed sleep

Wakefulness - Wake your sorry arse up

One of the primary driving factors of the onset of sleep or sleep latency is the production of adenosine. Caffeine is a well-known antagonist of adenosine and therefore many a wise word about not drinking caffeine after 3-4 pm as it has a half-life of 6 hours are well heeded (yes I know there are some of you that metabolise caffeine really well after that time with no impact on sleep, STOP SHOWING OFF).  Avoiding caffeine though out the day isn’t necessary and caffeine is a widely mis-understand compound that shows many beneficial effects, if you follow the rules for its consumption.

Often there is much focus on the role of melatonin and sleep induction and structures like the suprachiasmatic nucleus and waking. Melatonin does indeed promote sleep but so does adenosine and I think the supplementing of melatonin misses key biological functions that induce sleep more effectively and without the negative effects associated with its use.

Serotonin and melatonin confusion

 Sleep wake compounds

Sleep wake compounds

Just like the holistic health practitioner that suggests that coffee causes adrenal fatigue (it doesn’t but that’s another blog by itself), some practitioners recommend the use of 5HTP - tryptophan supplements (tryptophan converts to serotonin) for better sleep but this is misguided for the following reasons. It’s true that melatonin is a hormone of sleep and that it is derived from serotonin and that serotonin has a small but limited role in inhibiting the cholinergic system responsible for keeping you in an alert, thinking state. In the diagram below and born out of many studies is that serotonin is a powerful compound of wakefulness that synergises with histamine and the histaminergic system to bring you out of the deeper REM sleep, and start the process of waking you the hell up. The diagram from Brown et al (Brown, Basheer, McKenna, Strecker, & McCarley, 2012) highlights the complexities of the sleep wake compounds but also useful for highlighting serotonin's role (5HT) in the excitatory waking state. It’s also a great overview of the many areas and compounds that aren’t addressed in this blog. One thing that should become clear is that the neural structures controlling sleep are many and so are the interactions between hormones and other compounds of wakefulness. My advice below is not complete but merely a reflection of some of the simple changes that you can do (and which I have done with many clients) to create better sleep and recovery. 

Here are a few pointers on serotonin and melatonin.

  • Many people are aware of the fact that at least 95% of the body's serotonin is produced in the intestines - namely the enterochromaffin cells.

  • People associate serotonin as a hormone of calmness. 1) It’s not a hormone 2) well known side effects of serotonin excess are insomnia and anger.

  • Serotonin induces spasticity of the colons smooth muscle tissues

  • Eating excess muscle meats increases serotonin (as does eating poorly digestible foods), inflammation and can contribute to increased wakefulness by synergising with histamine.

  • Melatonin may be implicated in seasonal affective disorder due to increased levels in darker winter days. Sunglass wearing may pose similar issues (Alpayci, Ozdemir, Erdem, Bozan, & Yazmalar, 2012)

  • Supplementation with melatonin during the day can induce disruptive changes to fertility and also suppress thyroid hormone (Creighton & Rudeen, 1989).

  • Peak concentrations of thyroid stimulating hormone (TSH) occur at night and might be suggestive of thyroid hormone suppression induced by melatonin and other hormones. The pituitary responds by increasing TSH to bolster thyroid hormone supply.

Of course there are other compounds which include acetylcholine, GABA, oxycretin, histamine and many other areas of the central nervous system that could be mentioned but I have tried to stick to the mechanisms that can be changed and promote change in a short space of time.

If you find it hard to drift off, these are my suggestions as to why this might happen:

  1. You are eating foods that promote intestinal inflammation and increase serotonin and histamine.

  2. You are exposed to excess stimulus such as blue light, Wi-Fi or other source.

  3. Your blood sugar levels are not balanced and promote the stress hormones that liberate glucose from stored fats and proteins - adrenaline-glucagon-cortisol.

If you wake up at night the following might be also be an issue

  1. You are eating foods that promote intestinal inflammation and increase serotonin and histamine.

  2. Your blood sugar levels are not balanced and promote the stress hormones that liberate glucose from stored fats and proteins - adrenaline-glucagon-cortisol.

Point 2 may be a significant factor for many people and available efficient glucose production may be one of the most under-rated factors in both the onset of sleep and maintenance of sleep. Waking up to urinate at night is a feature of the diabetic like state. Poor blood sugar regulation requires, that instead of relying on blood and liver glucose stores, the stress response be relied upon to liberate energy from stored fats. This is an inefficiency that requires a stressed state. You should not be waking at night to go for a pee.

 Morning Cortisol profile

Morning Cortisol profile

You can see from the average nighttime cortisol profile that cortisol generally starts to rise around 2 am, steadily increasing prior to the onset of waking. If your ability to regulate blood sugar levels is compromised this can increase the burden to blood sugar regulation and increase waking further. The REM phase of sleep uses a similar amount of glucose as the waking state.

Here are some useful tips that I use with clients to promote better sleep and recovery.

  1. Take a look at the previous post on resolving digestion issues. This helps to take away some of the factors related to serotonin and histamine excess.

  2. If you are exercising hard, low carb, busy parent or whatever form of stress and therefore don’t manage your blood sugar levels, you don’t manage your sleep. If you struggle getting to sleep a sweet drink like milk and honey (yes the old wives tale works like a charm). A glass of fruit juice with gelatin is also good. Any pattern with something with sweet with a little protein/fat is useful.

  3. Add some salt - increased stress burdens the adrenal glands, usually though thyroid hormone suppression. Salt is wasted in this state and so is magnesium. Salt spares magnesium, so adding a little salt also helps magnesium regulation.

  4. If you wake during the night. This can be common when trying to resolve these issues as liver function and hormone regulation take a little time to adjust. Therefore having something sweet by the bed can help to help you re-enter sleep. Squeezy honey tube or pouch of juice with straw I find useful so that the juice goes straight down rather than covering my teeth.

  5. I have often found that progesterone and thyroid play a key role in sleep and many clients have benefitted from resolving the states of low progesterone/thyroid, which may not have resolved with food alone.

  6. Optimal blood sugar regulation often starts with eating breakfast to decrease adrenaline, glucagon and cortisol (Jakubowicz et al., 2015)(Levitsky & Pacanowski, 2013). Drinking a kale smoothie or coffee on an empty stomach is not the best way to break your fast and set up the day.

  7. Of course aspects of sleep hygiene related to no phones, WI-FI etc goes without thinking and go as far as turning your router off at night.So armed with some facts that you can decrease stress and improve sleep by eating sugar in the right amount, you can go and experiment for yourself.

References:

  1. Alpayci, M., Ozdemir, O., Erdem, S., Bozan, N., & Yazmalar, L. (2012). Sunglasses may play a role in depression. Journal of Mood Disorders, 2(2), 80. http://doi.org/10.5455/jmood.20120529055051

  2. Brown, R. E., Basheer, R., McKenna, J. T., Strecker, R. E., & McCarley, R. W. (2012). Control of Sleep and Wakefulness. Physiological Reviews, 92(3), 1087–1187. http://doi.org/10.1152/physrev.00032.2011

  3. Creighton, J. A., & Rudeen, P. K. (1989). Effects of Melatonin and Thyroxine Treatment on Reproductive Organs and Thyroid Hormone Levels in Male Hamsters. Journal of Pineal Research, 6(4), 317–323. http://doi.org/10.1111/j.1600-079X.1989.tb00427.x

  4. 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

  5. Levitsky, D. A., & Pacanowski, C. R. (2013). Effect of skipping breakfast on subsequent energy intake. Physiology and Behavior, 119, 9–16. http://doi.org/10.1016/j.physbeh.2013.05.006

Online:

7. http://raypeat.com/articles/articles/serotonin-depression-aggression.shtml

8. http://raypeat.com/articles/articles/serotonin-disease-aging-inflammation.shtml

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Is testosterone replacement therapy necessary?

Is Testosterone replacement therapy (TRT) necessary or symptom chasing? [embed]https://www.youtube.com/watch?v=KC0-xL0JVrI&feature=youtu.be[/embed]

In a world where it is increasingly normal to be convinced that we fall into a risk classification, need a treatment and can convince our doctor accordingly, negating any experience that he or she might have. The marketeers and economists that run pharmaceutical companies are doing a great job of increasing profits. Before we keep looking for the next wonder treatment we should take stock of what food and exercise can do.

Testosterone can be increased by some very simple strategies such as:

  1. Having adequate liver and vitamin A in the diet to assist in the conversion of cholesterol to pregnenolone - the base hormone responsible for production of testosterone and other androgens.

  2. Ensuring that adequate energy and thyroid hormone are available to maintain communication of the hypothalamic- pituitary- (signalling centres for hormone production-brain to testicles) gonadal axis.

  3. Understanding stress, sleep and interactions between excesses of estrogen and their impact on testosterone production.

  4. Less understood but increasingly keeping mobile communication devices out of pockets and bags that are close to reproductive tissue, including females (ovaries, endometrium etc), appears to be a pragmatic approach in the future. Steroid producing tissues have increased production of problematic compounds that may be prone to damage.

Here's some of the technical aspects to the situation that are taken from a recent assignment as part of my masters degree..

Introduction

Testosterone is a hormone found in both males and females but is the major reproductive hormone in men that also has a variety of other beneficial functions for maintaining physical and psychological aspects to health. Testosterone levels may decrease with disease and/or be part of an age related decline of output. The use of testosterone supplementation has increased substantially in recent years counter these states, primarily due to increased marketing as an agent of change for energy, strength, fat loss and sexual function. Whilst its use appears beneficial in some areas, caution has been recommended on the effects of T supplementation use and it’s effects on the cardiovascular system.

 Diagnosis

Testosterone (T) is the most important androgen found in males and produced primarily within the testes, when low it is defined as hypogonadism. Hypogonadism is classified as either primary, derived from the testes or secondary, which involves the hypothalamus, pituitary or derived from illness or disease. A low serum testosterone (<300ng/dL) is suggestive, but not definitive of hypogonadism and measurements of luteinising (LH) and follicle stimulating hormone (FSH) is used to establish a primary or secondary diagnosis (Crawford & Kennedy, 2016). A worry trend is that despite striking increases of testosterone prescription a substantial amount (approximately 29% in this review) of patients often fail to have their levels checked prior to undertaking testosterone replacement therapy (TRT). (Corona G, Rastrelli, Maseroli, Sforza, & Maggi, 2015). Additionally only 45 % had their testosterone levels checked during or post TRT intervention.

Low testosterone and cardiovascular risk

Previous studies have highlighted an increase in all cause mortality associated with low testosterone levels in men (Araujo et al., 2011). Conditions that increase risk of mortality related to low testosterone are increased abdominal obesity, inflammatory biomarkers, dyslipidaemia, diabetes mellitus and metabolic syndrome. However the diagnosis of an isolated low testosterone level should be qualified by ruling out other potential diagnosis such as long-term illness, nutritional deficiencies and other endocrine issues such as subclinical or overt hypothyroidism.

Testosterone supplementation and risks

A number of studies and meta analysis have demonstrated a number of beneficial effects of TRT which extend to increased sexual satisfaction, muscle mass, strength mood and metabolic function (Corona G et al., 2015) (Gagliano-Jucá & Basaria, 2017). However the suggested risk to increased CV adverse events have appeared vague in many studies and previous extrapolations/anecdotes between men having increased levels of testosterone (and therefore increased cardiac risk) and females having less testosterone and more oestrogen were not just problematic but incorrect. Many studies have correlated low testosterone to low biomarkers of health and increased cardiovascular disease (Pastuszak, Kohn, Estis, & Lipshultz, 2017) (Kloner, Carson, Dobs, Kopecky, & Mohler, 2016).

TRT reductionism and treating symptoms

A comprehensive review of the data compiled by Oskui et al (Mesbah Oskui, P., French, W.J., Herring, 2013) described the major CV implications of TRT which can be observed below. The authors draw attention to previously conducted studies, that did not show any relationships between low levels of testosterone and CV risk and suggest that both the subfraction of testosterone (Total T compared to Free T) and method of analysis for CVD were inappropriate and therefore unreliable for inclusion. 

Cardiovascular analysis Studies Major findings Association between T and mortality 8 8/8 studies found relationship between low T and increased all cause and CV mortality. Type 2 DM 6 6/6 studies showed improved insulin sensitivity through HOMA-IR/HgA!c and improved blood glucose Cholesterol 3 2/3 studies found no change to LDL/HDL from TRT Markers of inflammation (primarily C reactive protein CRP) 8 4/8 studies found reduced CRP Intima media thickness 8 8/8 found an inverse relationship between low T and IMT

The above studies reviewed by the authors, established a link between low levels of testosterone and increases in mortality (all cause and CV), insulin sensitivity and increases in intima media thickness that are resolved by TRT. Yet markers for lipids and inflammation markers such as CRP are less convincing. Hypothyroidism is related to low testosterone and hypogonadic states mainly through hypothalamic-pituitary dysfunction. Treatment of hypothyroid and subclinical hypothyroid states also resolves low testosterone and hypogonadic states, decreases intima media thickness, improves insulin sensitivity and decreases lipid levels (Crawford & Kennedy, 2016), (Krassas, Poppe, & Glinoer, 2010),(Donnelly & White, 2000) (Gao, Zhang, Zhang, Yang, & Chen, 2013). Is TRT the correct therapy for many males, given a) the rapid increases in often undiagnosed and prescription and b) when hypogonadic states, that have similar (cardiac) manifestations and are improved beyond the effects of TRT, are resolved with thyroid hormone?

Another factor concerning reliability of the studies used in previous meta analysis is the size to determine true risk between CV adverse events and TRT (Onasanya et al., 2016). The authors suggesting that to achieve a two-sided p value of 0.05 and power of 80% some 17664 participants would need to study to clarify any relationship. Observational data conducted over 5 years suggested that control groups treated with testosterone in short term had a lower mortality (HR 0.88 95 % CI 0:84 - 0.93) than controls (Wallis et al., 2016). From the meta analysis and other studies discussed above both age (>65) and predisposition to existing disease states may indicate the likelihood of adverse CV events when treated with TRT.

Another draw back of meta-analysis is the inclusion of data and bias produced by pharmaceutical companies that may not be adequately reflected or assessed. Much like cardiovascular end point studies being scarce. Testosterone studies that are funded by financial interests are usually in place to validate the benefits of TRT and fail to evaluate CV adverse events as end points. The increased adequate sample size needed to validate the safety and efficacy of this treatment often increase cost and decrease profit margin over time. The many studies that have been conducted so far, show much smaller sample sizes and a wide range of TRT delivery and dosing.

In a recent case crossover analysis that is not included in any current meta analysis, Layton et al (Layton et al., 2018) found a unique association between testosterone injections and short term cardio (and cerebrovascular) events in older men. Increased associations with myocardial infarction and stroke, post testosterone injection showed odds ratio (OR) were increased for all outcomes, OR =1.45 (95%: CI 1.07, 1.98).

Summary

Testosterone replacement does appear to have many positive effects on a number of markers related to cardiovascular health which include sexual performance, increased muscle mass, metabolic health, physical performance and decreasing mortality in a younger population. However, despite the many benefits of TRT the use of this therapy may have significant risk in late onset hypogonadal states, in ages >65 years of age, those susceptible to conditions associated with erythrocytosis and an association with acute cardiac events exists. It remains essential to ensure that not only adequate analysis of hypogonadal states are present but to ascertain if low testosterone levels are merely a symptom of other endocrine disturbances, such as hypothyroidism which has striking similarities to low levels of testosterone.

Want some more free resources on hormones?

References:

1.Araujo, A. B., Dixon, J. M., Suarez, E. a, Murad, M. H., Guey, L. T., & Wittert, G. a. (2011). Clinical review: Endogenous testosterone and mortality in men: a systematic review and meta-analysis. The Journal of Clinical Endocrinology and Metabolism, 96(10), 3007–19. http://doi.org/10.1210/jc.2011-1137

2.Basaria, S., Davda, M. N., Travison, T. G., Ulloor, J., Singh, R., & Bhasin, S. (2013). Risk Factors Associated with Cardiovascular Events During Testosterone Administration in Older Men with Mobility Limitation. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 68(2), 153–60. http://doi.org/10.1093/gerona/gls138

  1. Corona G, G., Rastrelli, G., Maseroli, E., Sforza, A., & Maggi, M. (2015). Testosterone Replacement Therapy and Cardiovascular Risk: A Review. The World Journal of Men’s Health, 33(3), 130–42. http://doi.org/10.5534/wjmh.2015.33.3.130

  2. Crawford, M., & Kennedy, L. (2016). Testosterone replacement therapy: role of pituitary and thyroid in diagnosis and treatment. Translational Andrology and Urology, 5(6), 850–858. http://doi.org/10.21037/tau.2016.09.01

  3. Donnelly, P., & White, C. (2000). Testicular dysfunction in men with primary hypothyroidism; Reversal of hypogonadotrophic hypogonadism with replacement thyroxine. Clinical Endocrinology, 52(2), 197–201. http://doi.org/10.1046/j.1365-2265.2000.00918.x

  4. Gagliano-Jucá, T., & Basaria, S. (2017). Trials of testosterone replacement reporting cardiovascular adverse events. Asian Journal of Andrology, 19(May), 1–7. http://doi.org/10.4103/aja.aja

  5. Gao, N., Zhang, W., Zhang, Y., Yang, Q., & Chen, S. (2013). Carotid intima-media thickness in patients with subclinical hypothyroidism: A meta-analysis. Atherosclerosis, 227(1), 18–25. http://doi.org/10.1016/j.atherosclerosis.2012.10.070

  6. Kloner, R. A., Carson, C., Dobs, A., Kopecky, S., & Mohler, E. R. (2016). Testosterone and Cardiovascular Disease. Journal of the American College of Cardiology. http://doi.org/10.1016/j.jacc.2015.12.005

  7. Krassas, G. E., Poppe, K., & Glinoer, D. (2010). Thyroid Function and Human Reproductive Health. Endocrine Reviews, 31(5), 702–755. http://doi.org/10.1210/er.2009-0041

  8. Layton, J. B., Li, D., Meier, C. R., Sharpless, J. L., Stürmer, T., & Brookhart, M. A. (2018). Injection testosterone and adverse cardiovascular events: A case-crossover analysis. Clinical Endocrinology. http://doi.org/10.1111/cen.13574

  9. Mesbah Oskui, P., French, W.J., Herring, M. J. et al. (2013). Testosterone and the Cardiovascular System: A comprehensive Review of the Clinical Literature. Journal of the American Heart Association. http://doi.org/10.1161/JAHA.113.000272

  10. Onasanya, O., Iyer, G., Lucas, E., Lin, D., Singh, S., & Alexander, G. C. (2016). Association between exogenous testosterone and cardiovascular events: an overview of systematic reviews. The Lancet Diabetes and Endocrinology. http://doi.org/10.1016/S2213-8587(16)30215-7

  11. Pastuszak, A. W., Kohn, T. P., Estis, J., & Lipshultz, L. I. (2017). Low Plasma Testosterone Is Associated With Elevated Cardiovascular Disease Biomarkers. The Journal of Sexual Medicine, 14(9), 1095–1103. http://doi.org/10.1016/j.jsxm.2017.06.015

  12. Roos, A., Bakker, S. J. L., Links, T. P., Gans, R. O. B., & Wolffenbuttel, B. H. R. (2007). Thyroid function is associated with components of the metabolic syndrome in euthyroid subjects. The Journal of Clinical Endocrinology and Metabolism, 92(2), 491–6. http://doi.org/10.1210/jc.2006-1718

  13. Udovcic, M., Pena, R. H., Patham, B., Tabatabai, L., & Kansara, A. (2017). Hypothyroidism and the Heart. Methodist DeBakey Cardiovascular Journal, 13(2), 55–59. http://doi.org/10.14797/mdcj-13-2-55

  14. Wallis, C. J. D., Lo, K., Lee, Y., Krakowsky, Y., Garbens, A., Satkunasivam, R., … Nam, R. K. (2016). Survival and cardiovascular events in men treated with testosterone replacement therapy: an intention-to-treat observational cohort study. The Lancet. Diabetes & Endocrinology, 4(6), 498–506. http://doi.org/10.1016/S2213-8587(16)00112-1

  15. Xu, L., Freeman, G., Cowling, B. J., & Schooling, C. M. (2013). Testosterone therapy and cardiovascular events among men: A systematic review and meta-analysis of placebo-controlled randomized trials. BMC Medicine, 11(1). http://doi.org/10.1186/1741-7015-11-108

 

Scar tissue - is it an issue?

Is scar tissue really an issue? Alongside myself, scars may be one of the most under appreciated and neglected structures, when it comes to assessing aspects of an individual's pain and movement limitations.   For many people, which include physicians, surgeons and often the owners of said scars, there’s an acceptance that the scar has healed and is not involved in any process of pain, strength or movement dysfunction. Dr’s and surgeons often assume that time enables optimal healing and patients simply forget about the previous trauma. Time may be a great healer but the healing is only partial - the nervous system always remembers. Writing this, reminds me of a client who had filled in all historical injury and trauma that he had experienced on my intake forms, which might have been a factor in his chronic back pain. It wasn’t until he took his top off and under questioning revealed that he had  donated his kidney to his brother some twenty years ago. It wasn't a big deal though as it was twenty years ago apparently.

This sequence of events has been summarised as homeostatic, inflammation, granulation and remodelling phases (1) which are undergoing symbiotic relationships with other structures and dependant on energetic, endocrine and other functions of the individual, which often depend on environmental stimulus. During the granulation and proliferation phase, sub-phases, which include collagen deposition, remodelling of blood vessels and tissues occur. It’s likely that during these phases the health and energetic response of the individual will dictate the capacity to regenerate and may also influence the layers of dysfunction that are present with scar tissue.

“ In childhood, wounds heal quickly and inflammation is resolved, in extreme age, or during extreme stress or starvation, wound healing is much slower and the nature of inflammation and would closure is different. “Ray Peat.

Unsaturated vegetable fats, serotonin and estrogen promote collagen synthesis and resulting fibrosis and keloid scars are associated with these states (3). Perhaps the capacity to organise energy and regenerate are instrumental in decreasing the associated dysfunctions that can be found in all scar tissue? Most Drs that I have spoken to just assume that after 12 weeks the scar has generally healed and that normally activity can be resumed. As a rule, there is no thought given to mechanical, pain sensitising or emotional constraints induced by the presence of the scar. It’s generally accepted that most scars have 80% tensile strength of the previous structure, but again might that too be a product of the quality of healing available to the individual?

“ The amount of disorganised fibrous material formed in injured tissue is variable and depends on state of the individual and tissue situation. “

In hypothyroidism, high levels of the pituitary hormone TSH (thyroid stimulating hormone) are known to stimulate fibrosis (1) Maintaining adequate thyroid hormone production promotes DNA transcription, optimal energy production, carbon dioxide production and probably decreases the proliferative effects of 'estrogenic' states that can be attributed to keloid scar formation.

The bigger the scar, the more likely the associated dysfunction? Perhaps the more disorganised tissue that exists, the increased likelihood of fuzziness between the central nervous system and output to structures associated with that scar. In scar tissue that has not been assessed or treated, it's relatively easy to induce weakness or stress to the surrounding tissues by a variety of stimulus which might include thinking and different types of pain,  touch or vectors of stretch that create neurological chaos or threat to to the individual.

Good therapy should allow for conversations between the clinician and patient that create stimulus that may (or may not) affect the output of surrounding structures associated with the scar. Poor feedback mediated by the scar might involve the following:

Emotional: Aspects of recall of the event that the individual finds upsetting.

Nociception/pain: First and second pain, visual or auditory, crude/fine touch, tickle/itch temperature, stress or recall od suffering responses to stimulus. (Involve pain feedback related to spinothalamic, spinotectal, spinohypothalamic and spinomesencephalic tracts)

Mechanical: Pressure, rebound, stretch, joint mechanoreceptors and other responses to tissue and structures. (Related to Golgi, Pacini, Ruffini and other dorsal column feedback pathways.)

Improving the optimal healing of scar tissue might involve aspects such as adequate carbohydrate, proteins, sunlight (or red light), carbon dioxide, thyroid, progesterone, vitamin A and E. Avoiding phytoestrogens and low carbohydrate diets would also be prudent.

Despite optimised nutrition and endocrine function, it’s likely that many scars leave some artefact that prevents the nervous system communicating with tissues. C - sections, episiotomies, appendectomies, laparoscopies and most surgeries, injuries or trauma leave a trace that needs to be resolved with the right therapy. Inhibition can be purposeful but restoration might need a little nudge from therapies like proprioceptive deep tendon reflex (P-DTR).

References:

  1. Kim, D., Kim, W., Joo, S. K., Bae, J. M., Kim, J. H., & Ahmed, A. (2018). Subclinical Hypothyroidism and Low-Normal Thyroid Function Are Associated With Nonalcoholic Steatohepatitis and Fibrosis. Clinical Gastroenterology and Hepatology, 16(1), 123–131.e1. http://doi.org/10.1016/j.cgh.2017.08.014

  2. https://emedicine.medscape.com/article/1298129-overview?pa=1ZDxXAnEOeNV9BUnYezdYpt49YJzASbxEvvw80YIDjlelzZDQj3XLvbI0V2MbTq%2FX8MwC0EECwzp432Skuf9qw%3D%3D

  3. http://raypeat.com/articles/articles/regeneration-degeneration.shtml

Sunlight, health and cancer

 The more you read, the more holes you find in many theories.

The more you read, the more holes you find in many theories.

Increasing sunlight exposure increases an individuals health and decreases cancer risk. In the last year or two I remember reading a quote from a professor of dermatology at a university in the U.S. who stated, “ There is no amount of sun that is good for the skin.” Clearly said professor skipped basic biology in secondary school or has had a lifetime of examining patients with excess PUFA (polyunsaturated fatty acids) in their diet, which is associated with increased incidence of skin cancer (there’s also a hopeful possibility that he was quoted out of context but I live in hope). Sun and skin cancer are clearly linked. Or are they? It doesn’t appear so clear cut. I first became interested in light around 2009 and its benefits to health after reading Female Hormones in Context by Ray Peat. His suggestions that sunlight can, “cure depression, improve immunity, stimulate our metabolism, while decreasing food cravings and increase our intelligence, ” (Peat, 1997) intrigued me to gain a deeper understanding.Whilst I was aware of the harms of an excess of UV light, which can damage skin but is essential for increasing vitamin D levels. The far-reaching benefits of the spectrum of red and orange lights were unbeknownst to me.

Seasonal affective disorder or SAD is well documented and the mechanisms may be due to a number of factors such as increases in serotonin and melatonin. People generally get sicker and more depressed in winter and light therapy appears to be a useful tool in overcoming some of the symptoms associated with mood, energy and immune system related issues. If light is so harmful, why is it we often need more in these times and why has sunlight become so vilified?

Sunlight appears to get a bad rap in an ever increasingly reductionist causal relationship, in as much as sunlight causes skin cancer. Therefore wear sunscreen and avoid it. However current literature suggestions are along the lines of; “Wearing sunscreen increases sun exposure and increases incidence of melanoma and skin cancer.” Like many other approaches this A to B inference neglects to mention other pertinent mechanisms that can be attributed to increased incidence of cancerous states.

Cancer is a well known metabolic disease that can occur when specific effects to cells, namely mitochondria and the electron transport chain (ETC - often termed respiratory defects which allows problematic features of metabolism to occur, increasing damaging compounds). Cancer can be a feature of poor differentiation. Damage to tissues can often require new tissue to be formed. If an architect informs the site manager how to build the structure from just the blueprints without appreciation of the surrounding land and features, you can’t always guarantee success of completion.

Promoting better conversations between structures     

Vitamin A - promotes cell differentiation (this is very important when damaged tissue is rebuilt), improves immune system function and optimal hormone function. A meta analysis in 2016 highlighted vitamin A’s protective functions and usefulness in protection against skin related disease such as melanoma through inhibiting malignant transformation and decreasing tumour size and improving survival rates (Zhang, Chu, & Liu, 2014). It’s important to note that retinol from liver sources is the effective compound in this action and not carotenoids. Other findings such as anaemia are synergistic with decreased vitamin A levels due to its critical role in the immune system and fighting infection (Semba & Bloem, 2002). Vitamin A has similar actions to organisational compounds such as progesterone and thyroid.

A question worth exploring - Does a vitamin A deficiency decrease differentiation and lead to a potential increase in cancerous type states when exposed to UV light?

Estrogen

Estrogen has been implicated in many cancerous states, primarily due to its role in tissue proliferation. When unchecked by levels of progesterone, it can be responsible for unwanted tissue growth and mutagenicity (Mungenast & Thalhammer, 2014) (Troisi et al., 2014). Levels can be increased due to external sources in the environment and through increased conversion of testosterone in adipose tissue to estrogen via aromatase in both men and women (Skakkebæk, 2003)(Cargouët, Bimbot, Levi, & Perdiz, 2006). The potential increases in cancerous states such as melanoma due to modulation of estrogen might be an easy target for excess levels of U.V. light to exert a negative influence in susceptible tissues. Therefore keeping estrogen low and utilising estrogen lowering strategies through food choices and avoidance of certain compounds can be useful.

Fat status of tissues.

I often found that when my diet was high in unsaturated fats my skin burnt extremely quickly. It’s been noted that people who often use sunblock often burn much quicker when in the sun without sunscreen. Increased consumption of unsaturated fatty acids appear to be linked to an increase in melanoma (Bourne, Mackie, & Curtin, 1987). Anecdotally I found that with a large decrease in PUFA my skin tolerates much longer bouts of sunshine before burning (not bad for a semi ginger pasty bloke from Kent!) , even in the intense middle-eastern heat. High fat diets, whether un/saturated also decrease mitochondrial activity and lower oxidative metabolism (Titov et al., 2016). It’s well known that vegetable oil consumption is linked to cancer (Niknamian, S., Kalamian, 2016) and heated vegetable oils that enter the body are already oxidised causing additional inflammation.

Perhaps melanoma is substantially increased when an individual has increased estrogen exposure, excessive amounts of unsaturated fatty acids in the skin and vitamin A deficiency but does that still implicate sunlight as the cause of skin cancer? The A to B scenario hopefully seems less convincing.

Modulating estrogen and decreasing PUFA in the skin is a step in the right direction. Increasing skin tolerance for longer days in the sun will be beneficial for many people. Using a homemade sun screen with minimal PUFA in can be useful for those wanting to spend extra time in the sun without damaging the skin and of course depending on the latitude, avoiding peak sun times is prudent to avoid excess UV light.

More information on resolving these issues can be found in the member’s area.

References:

Bourne, D. J., Mackie, L. E., & Curtin, L. D. (1987). Melanoma and Dietary Lipids. Nutrition and Cancer, 9(4), 219–226. http://doi.org/10.1080/01635588709513930

Cargouët, M., Bimbot, M., Levi, Y., & Perdiz, D. (2006). Xenoestrogens modulate genotoxic (UVB)-induced cellular responses in estrogen receptors positive human breast cancer cells. Environmental Toxicology and Pharmacology, 22(1), 104–112. http://doi.org/10.1016/j.etap.2006.01.002

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

Niknamian, S., Kalamian, M. (2016). Vegetable Oils Consumption as One of the Leading Cause of Cancer and Heart disease. International Science and Investigation Journal, 5(5).

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

Semba, R. D., & Bloem, M. W. (2002). The anemia of vitamin a deficiency: Epidemiology and pathogenesis. European Journal of Clinical Nutrition. http://doi.org/10.1038/sj/ejcn/1601320

Skakkebæk, N. E. (2003). Testicular dysgenesis syndrome. In Hormone Research (Vol. 60, p. 49). http://doi.org/10.1159/000074499

Titov, D. V., Cracan, V., Goodman, R. P., Peng, J., Grabarek, Z., & Mootha, V. K. (2016). Complementation of mitochondrial electron transport chain by manipulation of the NAD+/NADH ratio. Science, 352(6282), 231–235. http://doi.org/10.1126/science.aad4017

Troisi, R., Ganmaa, D., Silva, I. D. S., Davaalkham, D., Rosenberg, P. S., Rich-Edwards, J., … Alemany, M. (2014). The role of hormones in the differences in the incidence of breast cancer between Mongolia and the United Kingdom. PLoS ONE, 9(12). http://doi.org/10.1371/journal.pone.0114455

Zhang, Y.-P., Chu, R.-X., & Liu, H. (2014). Vitamin A intake and risk of melanoma: a meta-analysis. PloS One, 9(7), e102527. http://doi.org/10.1371/journal.pone.0102527

Being holistic versus (holistic) critical thinking.

sunrise-2.png

Is being 'holistic' an advantage to holistic critical thinking? It’s relatively easy to get drawn into a naturalistic fallacy of consuming all foods in their most raw natural state. Perhaps you’re someone who went from a fast food diet, where you didn’t feel your best, to consuming more whole foods, fresh fruit and vegetables? It’s easy to see how a switch and positive changes can occur in the short term. The next step is to start preaching to the masses how sugar is bad, how your life will be saved with green smoothies, nuts, seeds and coffee butt cleanses. For the record this is a waste of coffee and not to far from what I was preaching a decade ago. So what does it mean to be holistic?There’s a large movement within the health fitness and wellness industry (and lay people) that are drawn to  'holistic' thinking, and their definition is often enforced by the fallacy that everything in its most natural state is better for human health. This appears to include foods like nut milks (yes you can milk a nut), kale smoothies, seed oils like flax and undercooked broccoli and other greens, despite their negative effects on human health when consumed in substantial amounts. It’s a religion, and much like religion and with this mind-set it isn’t going to make you any healthier. I’ll make reference here to the late, great Beastie Boy, MCA who despite being a vegan and a Buddhist died far too early from throat cancer.

It is true that eating plenty of foods in their most natural state f(or some foods) can be important for health. But the image on the right highlights the faulty narrative of being holistic without thinking about the consequences. Fruits, vegetables, dairy products, meats and the like require minimal processing but in the quest for longevity, taste and profit, adding preservatives and flavour enhancers causes our food sources to become problematic. The so called ‘holistic’ folk get lost in this narrative urging your diet to become abundant in the rawest, greenest and brownest foods, that are most indigestible and contain potent inhibitors of biological function.

To integrate a level of holism into nutrition and function requires a level of critical thinking. What do these foods contain? How do they affect physiology? It’s well known that the brassica vegetables like broccoli, cauliflower and sprouts contain potent compounds that decrease energy output. These goitregens inhibit thyroid output and isothiocyanates found in cruciferous vegetables affects TPO or thyroid peroxidase, both of which are exacerbated when iodine uptake or restriction is present. Research tends to support these problematic effects (Choi & Kim, 2014)(Truong, Baron-Dubourdieu, Rougier, & Guénel, 2010), but much attention is focused on the smaller compounds that seem to work well in test tubes, rather than its global effects. As the environment becomes more stressful for biology do we need more building or reducing factors within our control?

The environment can be a harsh place. There are plenty of pollutants that have a negative effect on fertility, metabolism and other key endocrine aspects of health, some of which are industrial, others purposively added to food (arguably another form of industry) (Rajpert-De Meyts, Skakkebaek, & Toppari, 2000)(Upson, Harmon, & Baird, 2016). We can argue that the environment has always been a harsh place and adaptation has taken place as a response to selective pressures at the heart of evolution. Yet currently we are heading towards a tipping point, as environmental stimulants appear to be at the heart of acquired biological damage that is inherited by offspring. Cancer, fertility and other metabolic diseases are more common than ever and yet the approach is to keep seeking the magic bullet to ameliorate the fate that awaits many of us.

If we were to ask:

What enhances biological function, makes us more robust and allows us to have a stronger conversation with a stressful environment?

Rather than succumb to its stressors.

 The highway to health

The highway to health

A biological system in its best working order could be represented, as an infinite road stretching into the  distance, perhaps with the odd bump along the way or a slight deviation but an ability to get back on track is available. Compare that to the inhibitory T-junction where the body cannot function as the clear straight road, it deviates from its true organised direction. The journey is laboured and restrictive. The ability to flux and respond to stressors is key and adequate energy is an essential component of reorganisation.

Nutrition is an important factor for such conversations with the environment. Eating a diet that is dominated with foods that are difficult to digest, decrease energy availability and create more stress are not going to make chatting any easier. If we make the effort to understand what keeps a cell and its mitochondria functioning at its most efficient state, we can understand why aspects such as sugar, adequate protein, moderate exercise, light and other factors, can play a role in overcoming current stimulus that decrease function and increase disease states.

The following article is definitely worth a read for an understanding of the concepts that I have talked about. http://raypeat.com/articles/articles/vegetables.shtm

References:

Choi, W. J., & Kim, J. (2014). Dietary factors and the risk of thyroid cancer: a review. Clinical Nutrition Research, 3(2), 75–88. http://doi.org/10.7762/cnr.2014.3.2.75

Rajpert-De Meyts, E., Skakkebaek, N. E., & Toppari, J. (2000). Testicular Cancer Pathogenesis, Diagnosis and Endocrine Aspects. Endotext. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/25905224

Truong, T., Baron-Dubourdieu, D., Rougier, Y., & Guénel, P. (2010). Role of dietary iodine and cruciferous vegetables in thyroid cancer: A countrywide case-control study in New Caledonia. Cancer Causes and Control, 21(8), 1183–1192. http://doi.org/10.1007/s10552-010-9545-2

Upson, K., Harmon, Q. E., & Baird, D. D. (2016). Soy-based infant formula feeding and ultrasound-detected uterine fibroids among young African-American women with no prior clinical diagnosis of fibroids. Environmental Health Perspectives, 124(6), 769–775. http://doi.org/10.1289/ehp.1510082

Methylene Blue - Let’s play the blues.

Methylene blue - an overview: There’s been many times when I have recommended compounds/agents to create change in clients. Even the basic strategies of increasing sugar, not wearing sunscreen or the use of aspirin for improving energy and decreasing oxidative stress has moved the odd eyebrow to be raised. Objections often dissipate when presented with the line of reasoning and research that supports my recommendations. Effective clients will often do their own research and come back armed with significant questions for a better understanding of what is trying to be achieved. Research previously conducted by the Nobel scientist Albert Szent Györgi showed that previously damaged cells that produce efficient energy can be restored with methylene blue.

So with the tradition of raising more eyebrows let’s suggest the use of a blue dye that can be added to aquariums for improving marine life health. That’s right you put it in fish tanks. Why indeed would you not think of consuming glassfuls of the stuff?

Methylene blue (MB) is a dye that has shown promising results in the following areas:

  • Tissue hypoxia
  • Hyper dynamic circulation of the liver post cirrhosis
  • Improved low blood pressure states
  • Hepato-pulmonary syndrome
  • Anti malarial agent
  • Improves mitochondrial function
  • Detects parasites such as h-Pylori
  • With additional treatment of red light has anti-parasitic effects.
  • Anti-microbial-kills MRSA
  • Hepatitis C and other conditions also effectively treated in tandem with red light application.
  • Anti-Alzheimer’s agent- attenuates amyloid plaques and improves mitochondrial function.

MB is able to decrease both nitric oxide and guanylate cyclase, both exert their influence on smooth cells and tissue, explaining its role in reversing severely low blood pressure states ( Medically termed - catecholamine refractory vasoplegia)

If we look closely at a couple of the major mechanisms, we can see that from a metabolic standpoint MB has some interesting benefits. It decreases hypoxia or increases oxygen saturation within the body, whilst also improving mitochondrial energy production.

The respiratory/ electron transfer (ETC) chain, that is essentially the mechanism providing optimal use of oxygen, carbohydrate, fat, when this functions well, carbon dioxide is produced, which allows for optimal dissociation of oxygen from haemoglobin. When the respiratory chain is damaged, cells often have to switch to inefficient anaerobic sources of energy production, wasting sugar and increasing lactic acid, which continue to decrease aspects of cellular function.

Methemoglobinemia is a state where haemoglobin is unable to carry oxygen. MB reacts within the red blood cell and converts ferric ions, which have been oxidised, to its former oxygen carrying state. Additionally it helps to repair the ETC that is often damaged due to pollutant, poison or inefficient metabolic induced changes as seen in states of Alzheimer’s (Oz, Lorke, & Petroianu, 2009).

Another novel aspect of MB is the treatment of parasitic infection. MB absorbs and reacts with the spectrum of red light acting as an antimicrobial/parasitic agent.

“ Protozoa require the invasion of a suitable host to complete all or part of their life cycle.”

So what constitutes an appropriate host? I offer the following definition.

An individual or organism that is unable to assimilate and produce energy effectively, organise optimal cellular function and provide an immune response capable of expelling or eradicating an opportunistic parasitic/bacterial infection.

I quote Ray Peat with the following:

“ Occasionally you have very vigorous parasites that have intentions. If they encounter you in a state when your blood sugar is low, for example, the parasites might find an opportunity and start disorganising your system. So the competing systems’ lower system getting a foothold in a higher system, counts as randomness. The assumption of randomness is usually that everything is always random. What has been ordered is achieved at a high cost, the arrow of time for these people is that you have to expend energy to create order, and get things piled up in a certain way can only do that by expending energy somewhere else. "

MB and the use low level laser therapy (or LLLT which uses red or near infra red light) have a commonality with their ability to reduce the inhibitory actions of nitric oxide. This leads to enhanced cytochrome c oxidase action at complex IV of the ETC ( in English this means the enzyme that promotes better function of the cells that use oxygen efficiently), promoting increased cellular respiration and energy production (ATP). These dual actions appear to be an effective anti-parasitic treatment.

If your still running around taking a rucksack full of supplements, restricting energy and immune enhancing foods to kill parasites and candida, this may be a far more effective therapy to consider. It should be no surprise that that considering these actions, the use of MB is being investigated as a serious therapy in the fight against cancer. The biology of cancer can be attributed to metabolic defects/damage within the mitochondria leading to mutations.

Of course like any compound whether it be oxygen, water, broccoli or vodka certain doses are problematic. However these are generally high. For example doses used to treat malaria are suggested as 36-72mg/kg over 3 days (Meissner et al., 2006) and safe therapeutic doses are suggested as <2mg/kg (Ginimuge & Jyothi, 2010). Newborn babies seem susceptible to MB side effects such as skin discoloration, respiratory distress and other unwanted symptoms. However, the mechanisms of why this might happen, requires a blog alone. It also appears problematic to those taking SSRI’s and can increase serotonin uptake to toxic levels.

What I have learnt from taking MB.

I found that if I took doses of more than 5mg total within a day or two of each other, my urine turned blue. A self -limiting factor that probably suggests that I was taking too much. I also had the odd crazy dream. I generally found that a total intake of 2.5 mgs or around 5 drops 2-3 days per week seemed to serve me well. I titrated up and found the optimal dose, something which I strongly recommend doing for all.

I found that my pulse oximeter readings improved from a general SpO2 93-97 to regular 98. Which is interesting as one side effect previously suggested is the ability of MB to underestimate pulse ox readings. It’s prudent to imply that any therapeutic dose may only create change as the system allows. Therefore basics strategies such as effective blood sugar regulation, through regular eating and other strategies should be applied.

Ps it’s also great at reversing cyanide and nitrate poisoning in fish. Might it be useful in humans consuming too much bacon?

1. Ginimuge, P. R., & Jyothi, S. D. (2010). Methylene blue: revisited. Journal of Anaesthesiology, Clinical Pharmacology, 26(4), 517–20. 2. Meissner, P. E., Mandi, G., Coulibaly, B., Witte, S., Tapsoba, T., Mansmann, U., … Müller, O. (2006). Methylene blue for malaria in Africa: Results from a dose-finding study in combination with chloroquine. Malaria Journal, 5. http://doi.org/10.1186/1475-2875-5-84 3. Oz, M., Lorke, D. E., & Petroianu, G. A. (2009). Methylene blue and Alzheimer’s disease. Biochemical Pharmacology, 78(8), 927–932. http://doi.org/10.1016/j.bcp.2009.04.034 4. Ray Peat quote originally taken from a YouTube interview with Andrew Murray. (cant recall which one) 5. https://www.google.com/patents/WO2007038201A1?cl=en 6. http://valtsus.blogspot.ae/ contains over 2500 LLLT studies and is by far the best resource available on the actions of LLLT.

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

 

Gestational diabetes and metformin-Is that the best that medical thinking has to offer?

Gestational diabetes or elevated blood sugar is often treated with metformin to improve blood sugar levels and considered the standard approach to treating gestational diabetes. The research suggests that it has little negative effects on the pregnant mother. However, does significant risks to both mother and baby if the incidence of premature birth count? Here are a few aspects to consider regarding the use of metformin to control blood sugar during pregnancy. A study of patients receiving a dose of metformin, combination of Clomiphene citrate (CC) and metformin both faired better than CC alone for the induction of ovulation (Neveu, Granger, St-Michel, & Lavoie, 2007).  As the combined group showed no benefit compared to metformin alone, one might consider that metformin alone may be considered for the positive effects.

In another study metformin and diet interventions showed a significant outcome compared to non-metformin-diet interventions. The metformin diet showed a reduction of 14 adverse events in a group of 76 expectant mothers, compared to the non-treated group of 36 adverse events out of 76 pregnancies (Glueck et al., 2013).

Thatcher and Jackson (Thatcher & Jackson, 2006) compared pregnancies of 188 women. 61 experienced miscarriages and 11 of those had stopped taking metformin, suggesting other abnormalities beyond metformin’s actions. 81% of women with pregnancies before metformin, 67% had prior miscarriages. 37% of these also miscarried again. Whilst metformin appeared to show minimal effects to mother and foetus 22% were born prematurely.

Whilst metformin has shown favourable outcomes in PCOS states, questions around pertinent biological mechanisms should warrant further discussion. It’s well known that two key endocrine actions may be compromised during the failure to achieve full gestation. Estrogen induces hypoxia in the uterus (Peat, 1997) and failure to produce adequate progesterone to counter the effects of estrogen may be implicated in the commonly fragile time around weeks 9-10 of pregnancy and incidence of miscarriage.

A concern of metformin are its affect transplacentally. Metformin appears to influence testicular size in males and affects sertoli cells. In females it may also lead to decreased androgen synthesis. Birth weight percentile is also significantly lower in pregnancies treated with metformin (Bertoldo, Faure, Dupont, & Froment, 2014)I Metformin has generally appeared safe in expecting mothers but considerable concern should be made regarding its long term effects to offspring and development most notably to reproductive tissues.

Hypothyroidism is a key factor in maintenance of pregnancy and alongside progesterone, thyroid hormone deficiency can be implicated in poor cellular energetics, production of adenosine triphosphate (ATP) and blood sugar regulation. There remains much debate about the issue of subclinical hypothyroidism, values and when to treat and perhaps metformin’s role despite showing some promises may be treating a symptom related to insulin sensitivity.

So perhaps these questions might be more pertinent before prescribing an agent that shows potentially negative effects to the fetus?

  1. What is the nutrition of the mother, is it enough and does it contain enough nutrients to enhance/maintain adequate progesterone/thyroid production?
  2. Is estrogen increasing at a rate that suppresses progesterone/thyroid levels and persistently decreases insulin sensitivity?
  3. Is there enough carbohydrate in the diet to ensure that carbohydrate is effectively utilised instead of persistent conversion of fats, increasing overall stress to both mother and fetus?
  4. Are the values of hypothyroidism and the identification of subclinical/functional hypothyroid factors appropriate?
  5. Is gestational diabetes a reflection of the above points?

The use of metformin, without questioning these mechanisms, remains at best a reduced treatment that fails to address a range of biological interactions and function.

References:

Bertoldo, M. J., Faure, M., Dupont, J., & Froment, P. (2014). Impact of metformin on reproductive tissues: an overview from gametogenesis to gestation. Annals of Translational Medicine2(6), 55. http://doi.org/10.3978/j.issn.2305-5839.2014.06.04

Glueck, C. J., Goldenberg, N., Pranikoff, J., Khan, Z., Padda, J., & Wang, P. (2013). Effects of metformin-diet intervention before and throughout pregnancy on obstetric and neonatal outcomes in patients with polycystic ovary syndrome. Current Medical Research and Opinion29(1), 55–62. http://doi.org/10.1185/03007995.2012.755121

Neveu, N., Granger, L., St-Michel, P., & Lavoie, H. B. (2007). Comparison of clomiphene citrate, metformin, or the combination of both for first-line ovulation induction and achievement of pregnancy in 154 women with polycystic ovary syndrome. Fertility and Sterility87(1), 113–120. http://doi.org/10.1016/j.fertnstert.2006.05.069

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

http://raypeat.com/articles/articles/glucose-sucrose-diabetes.shtml

Thatcher, S. S., & Jackson, E. M. (2006). Pregnancy outcome in infertile patients with polycystic ovary syndrome who were treated with metformin. Fertility and Sterility85(4), 1002–1009. http://doi.org/10.1016/j.fertnstert.2005.09.047

What is functional hypothyroidism?

You won’t find the term functional hypothyroidism in the medical literature, or at least not yet. Primarily due to clinical hypothyroidism being bound to a rigid assessment usually diagnosed by the blood test thyroid stimulating hormone or TSH. TSH secretion is controlled by synthesis of thyroid releasing hormone or TRH in the supraortic and supraventricular nuclei of the hypothalamus. TRH is transported to the anterior pituitary by the hypothalamo- hypophysial portal system where it stimulates synthesis of TSH. T4, T3 and TRH control the secretion of TSH (Gardner et al., 2011).

TSH production can also be affected by TSH receptor damage, medical drugs, disease states, iodide, blood glucose levels and other circulating hormones TSH may also be affected by environmental pollutants and heavy metals (Llop et al., 2015).  Metabolic disease and increases in Body Mass Index appear to be correlated with an increase in TSH levels (Ruhla et al., 2010).

Often, you will see clear links and studies to key micronutrients such as zinc, selenium, iodine and other important co-factors. These deficiencies can exist demographically but usually in westernised societies, there deficiency can be linked to impaired absorption rates, perhaps linked to digestive dysfunction and other factors.

“Measuring the amount of thyroid in the blood isn’t a good way to evaluate adequacy of thyroid function, since the response of tissues to the hormone can be suppressed (for example, by unsaturated fats) (Peat, R.1999).

 Dietary factors such as unsaturated fatty acids in the diet may potentially be one of the most overlooked factors that supress thyroid function. Other factors such as caloric restriction, stressful environments, over exercising and other factors are some of the others. It’s well known that in certain areas of hormone dysregulation such as menstrual cycle irregularities, oligoamenorrohea (loss of cycle), anovulation (failure to ovulate) and lack of libido and fertility in both men and women,  can be attributed to poor energy intake and environmental factors (Nieuwenhuijsen et al., 2014) (Skakkebæk, 2003). Dietary factors have synergy with hormonal imbalances perpetuating high levels of estrogen.

The functional suppression of thyroid function by unsaturated fats, eating a so-called healthy diet (full of uncooked brassica vegetables, nuts and seeds) orthorexic states and other factors is largely ignored by physicians.

I can say with some certainty, after completing postgraduate studies at university with a number of Doctors, that diet and inhibitory factors of diet rarely get assessed when it comes to assessing energy and thyroid function.

A persistent functional hypothyroid state, induced by unsaturated fats may lead to the pre-diabetic and diabetic states induced by an inability to utilise carbohydrate and the preferential shift to use of fats instead of sugars as suggested in the Randle or glucose fatty acid cycle (Randle, Garland, Hales, & Newsholme, 1963). Increased cortisol, oxidation, decreased carbon dioxide and an increased stress on the oxidative system, could potentially lead to glycolysis and an increase in lactic acid, further increasing damage, stress and further suppression of thyroid function.

Measurement of thyroid blood tests remains inaccurate and problematic without the inclusion of a variety of symptoms and previously accurate assessment, such as basal metabolic rate, body temperature and pulse. The suppression of both thyroid and adequate energy states will always remain.

As the common approach for diagnosing hypothyroidism is having TSH above 4 or 5 mmUL and the preferred treatment is to supplement with synthetic levothyroxine. How much change can you realistically achieve if you fail to address the supressed metabolism induced by diet, an individuals susceptibility to stress and their own environment?

 

References:

Gardner, D. G., Shoback, D. M., Greenspan, F. S. et al .(2011). Greenspan’s Basic and Clinical Endocrinology. McGraw Hill.

Llop, S., Lopez-Espinosa, M. J., Murcia, M., Alvarez-Pedrerol, M., Vioque, J., Aguinagalde, X., … Ballester, F. (2015). Synergism between exposure to mercury and use of iodine supplements on thyroid hormones in pregnant women. Environmental Research, 138, 298–305. http://doi.org/10.1016/j.envres.2015.02.026

Nieuwenhuijsen, M. J., Basagana, X., Dadvand, P., Martinez, D., Cirach, M., Beelen, R., & Jacquemin, B. (2014). Air pollution and human fertility rates. Environment International, 70, 9–14. http://doi.org/10.1016/j.envint.2014.05.005; 10.1016/j.envint.2014.05.005

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

Randle, P. J., Garland, P. B., Hales, C. N., & Newsholme, E. A. (1963). The glucose fatty-acid cycle its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. The Lancet, 281(7285), 785–789. http://doi.org/10.1016/S0140-6736(63)91500-9

Ruhla, S., Weickert, M. O., Arafat, A. M., Osterhoff, M., Isken, F., Spranger, J., … Möhlig, M. (2010). A high normal TSH is associated with the metabolic syndrome. Clinical Endocrinology, 72(5), 696–701. http://doi.org/10.1111/j.1365-2265.2009.03698.x

Skakkebæk, N. E. (2003). Testicular dysgenesis syndrome. In Hormone Research (Vol. 60, p. 49). http://doi.org/10.1159/000074499

 

An energetic approach to restoring gut function: Part 1.

Let’s kick this blog off with a question as to whether or not an energetic approach to restoring  gut function is useful or should we rely on testing and supplements? Let me clarify, that I have had my fair share of success stories with a reduced and diagnostic approach to improving gut health. Just like I have also had my fair share of kickbacks from the laboratory for recommending their tests. At one point I was using nearly 200 stool tests per year and making a little cash on the side. Many of the tests worked in isolating some specific disturbance to their gut bacteria, presence of a parasite or elevation of putrefied fatty acids. A ‘cleansing’ diet was promoted and a few supplements for good measure created some short term change whilst the client was in my care. But here’s why the long-term approach to that type of assessment and treatment may not be the best response. A standard functional medicine approach  after spending quite a lot of cash on an integrated stool test is using the 4 R approach.

Remove (offending parties)- spend money on supplements

Restore function- spend money on supplements

Re-inoculate - spend money on nice expensive probiotics

Repair gut lining- spend money on supplements

Regurgitate. Ok the 5th one is mine but no supplements needed.

By taking this approach, an important question is not asked of the individual. Why is this person experiencing an overgrowth of bacteria/SIBO, parasitic infection, endotoxin overgrowth, inflammation and degradation of the bowel lining? I like to think that it is not because of the easy kickbacks FM practitioners are getting for the lab tests and supplements they recommend? So what is the persons level of biological energy and immune system function that allows their digestive system to get in such a state. We know there are some usual suspects. Food, stress or alcohol perhaps?

The typical gastrointestinal complaints people came to me with, were bloating, excess gas, constipation or irritated loose stools combined with poor energy. It was Ilya Mechnikov who originally stated that death starts in the bowel or colon and there’s’ certainly many degenerative and inflammatory conditions that appear at the last stop to poopy central. But is the bowel the main driver of this dysfunction? Many of the symptoms that I recalled earlier are also key symptoms of an energetic and perhaps a thyroid dysfunction. So instead of reaching for our drastic 4 R protocol with an expensive poo test lets consider the following.

 The likes of Broda Barnes and Ray Peat have highlighted how a lack of energy, either from a low or inappropriate food intake or a dysfunctional hypothalamic-pituitary-adrenal-thyroid axis can be evaluated by assessing body temperature and the combination of pulse. Additional information on Thyroid and TSH evaluation can be found here.

Most people are aware that when they get stressed or exercise, blood is shunted away from the digestive system to the periphery and other working tissues. Even the concept of high Adreno-corticotrophic hormone (ACTH), cortico releasing hormone (CRH) and adrenal production of cortisol is becoming common place in work and gym environments alike. These hormones suppress thyroid hormone and the energy compound ATP that provide energy for tissues.

It’s also well known that low energy states create tight painful muscles that are difficult to relax and one might be able to apply that line of thought to the smooth muscle tissues that regulate bowel contractility. Therefore a low energy state that does not allow for adequate energy production will not allow adequate digestion and bowel function to occur. Cold hands and feet can be a symptom of not eating enough carbohydrate and protein.

If the cold hands and feet, low body temperature, fatigue, constipation don’t resolve from eating energy rich meals that contain plenty of fruit and contains little of the foods that promote the bowel irritants histamine and serotonin (nuts, seeds, vegetable oils, grains, gluten free products, beans and pulses). Then, often factors that influence the hormones such as thyroid, estrogen and progesterone may need a deeper consideration.

I drafted a little flow chart that will be helpful for some quick strategies on what might be happening but what I would like to focus on the low energy state that might have its source from a food or hormone factor or perhaps both. Instead of using a strategy like the 4 R approach, these simple questions can help guide you to understanding whether it is the foods that you eat or an energetic factor that could be causing your digestive system to suffer. It's not a complete algorithm but it does offer some simple solutions that have helped plenty of people resolve digestion and energy issues.

Foot note: I haven't needed a stool test with a client for over 4 years now following this chart.

 

In part 2 I will elaborate on foods and basic supplements that can be used to resolve most long standing digestive issues and understanding other hormone actions that create digestive discord.

References:

Lokaj, J., & John, C. (2008). [Ilya Ilich Metchnikov and Paul Ehrlich: 1908 Nobel Prize winners for their research on immunity]. Epidemiologie, Mikrobiologie, Imunologie : Casopis Spolecnosti pro Epidemiologii a Mikrobiologii Ceské Lékarské Spolecnosti J.E. Purkyne, 57(4), 119–24. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/19069024

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

Peat, R. (2006). Autonomic Systems. Retrieved from raypeat.com/articles/other/autonomic-systems.shtml

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

Health, Thyroid and TSH. Assessing and treating the thyroid.

What is the impact of thyroid hormone on health?Increasingly health is defined by a bunch of arbitrary numbers. High cholesterol? That’s not normal take a pill. Low iron? Here take this iron supplement. In Ivan Illich’s book, Limits to Medicine- Medical Nemesis, Illich makes the reader fully aware of his disdain of medical check ups - " The medicalisation of prevention thus becomes another major symptom of social iatrogenesis. It tends to transform personal responsibility for my future into my management by some agency."

Instead of heavily reliant systems on numbers and markers. Should we not look to improve qualitative and quantitative pairings to get a better picture of health and improve outcomes? The last ten weeks of my life have been wrapped up in a post graduate diploma in endocrinology. Getting a better picture of how clinicians tackle complex areas has been a rewarding but at the same time frustrating area of study.

Sometimes the questioning has been a down the lines of - This patient has this endocrine feature, what are the medication used, which medications interfere, what surgical options can be pursued and what is the follow up? What is frustrating for me is there is little effort to understand why? Why? Why Donald why? Diet, stress and environmental aspects of hormonal health are often forgotten about, because the goal of getting that client back into the window of numerical health takes priority. But what if we took a better look at the why? Might it not yield better long-term outcomes for the patient?

I have a special interest in thyroid function, motivated by the writings of Ray Peat, Broda Barnes, Mark Starr and others. There’s a significant amount of work discrediting the role of combined T4/T3 therapy and in particular natural desiccated thyroid (NDT). In many endocrine textbooks the elevation of the active form of thyroid hormone, T3 was elevated significantly post NDT treatment.

A confounding factor in this assumption was based upon a previously incorrect conversion which can still be found in endocrine textbooks stating that 1mg of NDT was equivalent to 1ug of LT-4. There is recent evidence available showing a patient preference for NDT, which showed improved outcomes to weight loss, energy, happiness, sleep and memory (Hoang, Olsen, Mai, Clyde, & Shakir, 2013).

A reliance on TSH, T3 and T4 levels alone may be ineffective at analysing the effectiveness of combination therapy in comparison to synthetic monotherapy treatment of hypothyroidism. Additionally this study highlights the inaccuracy of the assumed conversion of 1mg: 1ug. Using more accurate 3rd generation TSH assays yields a suggested ratio of 1.47 mg’s to 1ug. This may explain the lack of effectiveness in previously conducted trials and the conclusion that increased transient T3 levels were decided as unacceptable. NDT in many cases may offer a better solution than synthetic thyroid hormone after all

Potential mechanisms of improvement may also lie in the actions of T1 and T2 and assumptions based solely on TSH, T3 and T4 may not explain the benefits recorded in this and other studies.      

Another pitfall of number reliance is well known in the reference of thyroid stimulating hormone (TSH). TSH is considered the gold standard for hypothyroid diagnosis but its limitations have become increasingly prevalent due to its production via the stimulating centers from TRH (thyroid releasing hormone) from the hypothalamus and then TSH from the pituitary, if a problem exists at the periphery the likelihood of getting an accurate assessment is diminished. A normal TSH reading is defined as 0.4-4.5 mU/L but generally many Doctors do not consider someone hypothyroid unless they present with a TSH over 4 mU/L.

Increasingly some Doctors are becoming aware of the reduction of hypothyroid symptoms when TSH is kept below 1mU/L and some evidence suggests that even at 0.5 mU/L (lowered but suppressed) is ideal to ensure that hypothyroid symptoms are decreased (Pantalone & Nasr, 2010).

Me? I am going to go back and contradict myself and say that numbers are useful. The basal temperature test with a cheap thermometer, as championed by Broda Barnes still suggests a good window of function of the thyroid test. 36.5 to 37 degrees is considered normal and reflects a well functioning metabolism. Couple that with a pulse rate test and you can also get a good indication of cortisol. So I am not against the numbers. I just think we need to ask better questions before we accept them as absolutes.

References:

Hoang, T. D., Olsen, C. H., Mai, V. Q., Clyde, P. W., & Shakir, M. K. M. (2013). Desiccated thyroid extract compared with levothyroxine in the treatment of hypothyroidism: A randomized, double-blind, crossover study. Journal of Clinical Endocrinology and Metabolism, 98(5), 1982–1990. http://doi.org/10.1210/jc.2012-4107

Illich, I. Limits to Medicine - Medical Nemesis. Marion Boyars. 1976.

Pantalone, K. M., & Nasr, C. (2010). Approach to a low tsh level: Patience is a virtue. Cleveland Clinic Journal of Medicine. http://doi.org/10.3949/ccjm.77a.10056

 

Can a bad smell create pain, dysfunction and weakness?

We know about the feedback of pain and painful stimulus (nociception) and the creation of pain to warn us but what about the effects of noxious and more subtle smells on the nervous system? Over the last few years I have found that nothing ceases to amaze me when it comes to the human body. As it becomes possible to dissect systems and assess interactions of specific stimulus, observing the input/output relationship between stimulus and body. Pain stimulus is observed to be chemical, thermal or mechanical in nature. Please bear with the technicalities before I explain the simplified mechanisms or skip to the last part of the blog, if you get bored!

There are many factors that contribute to a patient’s perception and physical feeling of pain. Pain is the central nervous systems response to an event that has the capacity to injure the tissues of the body. Nociception or pain can be qualified from the following pathways.

The ‘First’ pain is usually a withdrawal mechanism (Nociceptive Withdrawal Reflex or NRA) mediated by the neurotransmitter glutamate and utilises the neospinalthalmic (new pain) tract in the anterolateral system or ALS. This typically lasts less than 0.1 of a second and the signal, suggested to be dampened in the substantia gelatinosa, an area found in the dorsal aspect of the spinal cord. Think about that sharp initial pain experienced causing you to move away from a stimulus, which has been detected by free nerve endings.                               Smelly pain

The ‘Second’ pain is also part of the ALS but is part of the paleospinalthalmic tract (old pain). It typically takes over from the initial first pain/neo. It is mediated by the compound substance P and can be associated with that long, lingering pain experienced from an injury.

In addition to pain, we have the capacity to assess many other features of mechanical distortion such as pressure, stretch and touch. The Dorsal Column Medial Lemniscus or DCML, allows the nervous system to provide adequate feedback to tasks and environmental stimulus.

Another part of the pain detection system is the trigeminal chemosensory system, which has nociceptive/pain and temperature pathways that feedback to cranial nerve five, called the Trigeminal nerve (CNV). When a noxious or toxic substance is processed by the neurons in the mucosal areas of the nose, mouth, eyes and lips it is relayed into the thalamus. The VPMN (or ventral posterior medial nucleus) relays signals to the sensory cortex and provides responses, such as watery eyes, sneezing and withdrawal

When we inspire air with small particles of pollutants, they pass from the lungs into the blood stream. Although the blood brain barrier is supposed to prevent any unwanted chemicals, crossing from the blood to the brain; the Circumventricular organs present an area that does not have the capacity to restrict compounds that can create dis-organisation of neurological signals entering and leaving the brain. The area postrema, also has a chemosensory role to initiate vomiting to deal with exposure to harmful compounds

So let’s have something a little easier on the eyes and brain to read now. For example:

Perhaps you are walking across the road in heavy traffic. Sucking up all the pollutants such as benzene, carbon monoxide and other waste products of burning fossil fuels into your lungs as you find your way from one side of the road to another.

For a few seconds your brain, exposed to the onslaught of pollution, has a hard time processing the compounds that have made their way into areas such as the pineal gland or chemoreceptors that can induce vomiting in response to a noxious stimulus.

You are in a rush and bump into someone, his or her shoulder hitting you firmly in the chest. It was slightly painful but you don’t really notice it, the pain pathway, along with pressure, stretch and touch receptors provided some form of feedback. The brain, perhaps still not capable of processing this feedback due to the short exposure of increased pollutants, is just trying to get on with the milieu of everything else that your body demands of it.

Meanwhile the pectoralis muscle, which is being used with each step that you take, has been exposed to increased pressure, a state of contraction or small window of pain that necessitated a withdrawal reflex. The intrafusal muscle fiber that monitor both stretch and contraction now have increased signal towards sustained contraction due to the chaos of external compounds that entered areas of the brain.

So now we might have some level of muscle dysfunction. We probably don’t even know about it. That level of muscle dysfunction now increases and decreases tension demands to receptors found in the ligaments and tendons. The joint mechanoreceptors have a different signal. The skin exteroreceptors perhaps have a different signal. There’s no pain to remind us of the event. In fact we have now gone to the gym and started doing a bunch of push-ups or gone shopping for food and simply carrying the bag home with that hand and shoulder. This doesn’t create pain, but simply sets the foundation for increased areas of dysfunction from distorted neurological signalling.

The concept of this neurological/chemical chaos is often referred to as ‘brain fog’. It seems to be in the literature for many reasons, blood sugar issues, gluten, estrogen (PMS and menopausal females are particularly susceptible) and other factors. It’s also possible that brain fog can be created from specific food stressors, once again eliciting the same response, proposed in the heavy traffic.

Some might say, how can the body be so fragile? Surely we are more robust than that? But it is possible to create these specific dysfunctions but they can be unravelled. Understanding specific stimulus can give us a solution to what dysfunction exits. We might never find out how it came about but a thorough history taking can help to influence where we assess and how to treat it. This is where a technique like P-DTR or Proprioceptive Deep Tendon Reflex, developed by Dr Jose Palomar is unique and effective at uncovering specific neurological dysfunction.

If emotions, visual, auditory, mechanical, chemical and pain factors perpetuate dysfunction, then using those stimulus can pose an effective form of assessment and treatment.

  1. Palomar, J. Proprioceptive Deep Tendon Reflex: Course Notes.
  2. Purves D et al Neuroscience 5th edition. Sinauer Associates 2012
  3. http://www.neurology.org/content/77/12/1198.short

How to improve sleep-wake cycles.

Do you need to improve sleep? Why is it that sometimes, with the best intentions of going to bed early, we either find ourselves struggling to enter a sleep cycle, or wake up, deep in the hours of darkness? The prominent stress researcher Robert Sapolsky (Why Zebras don’t Get Ulcers) writes fondly of his near death experiences, of little sleep from the arrival of his newborn child. It’s no surprise that security and intelligence operatives use a lack of sleep to disorientate prisoners. Just one nights lack of sleep from me and I will tell you anything! Despite the will to nod off, why is it that many people suffered from poor sleep, or struggle to enter sleep cycles?

Before I delve into some brief hormonal issues that can be manipulated to ensure a deeper sleep it’s worth noting that darkness itself is a stressful experience and we produce many restorative hormones during sleep to combat the metabolic stress of darkness. Therefore one essential component of adequate sleep is exposure to sunlight on a daily basis. This ensures uptake of vitamin D and exposure to the deeper penetrative orange and red lights, which help to restore metabolism and healing of cells. An old blog on light therapy.

Over the years I have found the following issues associated with poor sleep.

  • Low blood sugar levels
  • Increase in compounds of wakefulness
  • Exercise late at night
  • Excessive work stress/blue light exposure
  • Exposure to EMF-electromagnetic stress and Wi-Fi
  • Poor sleep and its vicious cycle
  • Emotional Stress

There are several models to be aware of when it comes to sleep theory and the phases of sleep are categorised as

NREM – Non rapid eye movement- pre REM sleep.

REM - Rapid eye movement- this is the deep restorative part of sleep Active wake

Neurotransmitters and hormones associated with sleep:

Acetylcholine – AcH is the neurotransmitter associated with Rapid Eye Movement or REM sleep.

Serotonin – 5HT this neurotransmitter along with HA is associated with wakefulness.

Norepinephrine/Noreadrenaline - Ne - Hormone of wakefulness.

Gammaminobutyric Acid – GABA. GABA’s role in sleep is well documented but levels vary depending on location of the brain. It’s role is known in decreasing wakefulness and also decreasing deeper REM sleep and involved in producing wakefulness. Histamine- HA involved in wakefulness.

Hypocretin Orexin- PCT /O Involved in wakefulness.

Adenosine- AD involved in entering NREM sleep.

Here is a rough depiction of key Neurotransmitters of REM and NREM sleep. Other neurotransmitters of wakefulness such as Histamine, Serotonin and noreadenaline (hormone) are not depicted but are elevated in waking state and should be lower during sleep cycles. It’s worth noting that the use of serotonin in mood related disorders such as depression is a key agent in insomnia like states.

 

 

 

 

 

 

 

Common sleep disorders

Insomnia:  The inability to sleep restfully and I would categorise a good nights sleep from 6-9 hours depending on your own needs. The ability to enter deep sleep is dependant on many factors such as hormones, neurotransmitters, stress and available energy. It’s worth noting that the regenerative aspects of REM sleep and brain function have been shown to use as much glucose as when awake. Maintaining adequate available energy is key to getting sound-nights sleep.

Sleep apnoea: inability to enter REM sleep due to issues associated with optimal breathing. Obesity and sleep apnoea do seem to correlate and there is a suggestion of structural abnormalities in a small section of people.

The role of sleep in disease prevention

Sleep's role in psychiatric disorders, depression, metabolic disease and addiction are well documented. A key feature of a lack of sleep, besides on-going fatigue and failure to regenerate is the elevation of adrenalin and cortisol. Elevated levels of cortisol are well known to decrease thyroid function, which can have a significant effect on levels of circulating thyroid hormone and energy production (key to regulation of sleep). The mechanism can tie in with its pervasive actions on management of blood sugar levels. Another noted effect from sleep loss is that we tend to overeat more when tired, which could impact weight gain (and if thyroid is part of the vicious cycle, weight loss becomes increasingly difficult).

Lack of quality sleep can therefore be responsible for an increasing amount of deleterious conditions, such as hypothyroidism, diabetes and obesity, other hormone dys-regulation and cardiovascular disease. Ascertaining whether the issue initially stems from a hormone imbalance can be key in resolving sleep wake issues.

Drugs

There are a variety of drugs on the market that help to improve onset of sleep, however if you seek to improve the biological mechanisms of sleep and perhaps look to the list suggested below, you may find that your sleep improves, without the need for medication.

Cognitive behavioural therapy

The role of CBT in reducing Insomnia has shown effective results even more so than prescriptive medications. Whilst the treatment is not determined whether it effectively targets the mechanics of insomnia its success suggests provides a more desirable approach than long term insomnia medication.

What can you do?

  • Understand the link between production of inflammatory neurotransmitters such as Histamine and Serotonin and seek to lower them. This may be through diet adjustment or exposure to problematic chemicals/hormones.
  • If you get to sleep but wake up, this may be due to poor available energy. Maybe from a low carb diet, low thyroid function and poor production of energy. You may find having something light like a glass of milk with honey, or fruit juice with gelatin may help out. Salt also helps to decrease adrenalin production
  • Wi-Fi, blue light exposure, electromagnetic stress all play their part in interfering with stress and how the cells function. Stopping their use several hours before sleep can help. Do turn off Wi-Fi in house and no phones or electric devices by your bed.
  • Avoid stimulus such as caffeine or exercise in the evening, if you have sleep issues. Caffeine decreases production of adenosine.
  • If under emotional stress, a slow walk before bed may be a useful idea combined with ensuring adequate blood sugar levels are met.

References:

Neurobiology of Sleep. Course notes. Duke University. 2015.

Peat, R. From PMS to Menopause. Female Hormones in Context. 1997

Sapolsky R. Why Zebras don’t get Ulcers. St Martins Griffin. 1998

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2941414/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3443758/

http://www.ncbi.nlm.nih.gov/pubmed/27091535

 

Muscles, pain, hormones and other stuff.

As a therapist who works within the fields of pain, movement, energy and digestion I have seen my share of pain and muscle dysfunction in clients. As my exposure to these situations increase, I realise more than ever, that the muscles are very rarely the problem. Specific muscle dysfunction usually boils down to spindle cell

Thyroid pic

dysfunction and notably Nuclear Bag Fibres (NBF) and Nuclear chain Fibres (NCF). The primary roles of these structures are related to stretch and contraction of muscle function. There can be other factors involving neuro transmitters, involved in nocicpetion such as glutamate, utilised in the withdrawal reflex and often referred to as first pain, (also known as Neospinalthalamic tract located in the Anterolateral system or ALS) and lasting, less than a tenth of a second. Problems can arise when the following pain pathway, called second pain (or Paleospinalthalmic tract also part of the ALS) has problematic feedback with first pain, this is mediated by Bradykinin.

Further complexities arise with serotonin and other structures associated with pain such as the Amygdala and Peri Aqueductal Gray (PAG) that are beyond the scope of this short blog. However a common, over looked feature of pain, may arise with hypothyroidism .

Low thyroid function can be classified effectively with assessment of a basal temperature test and a reading of between 36.6 and 37 degrees. Most blood tests designed to measure thyroid hormones such as TSH, T3, T4 and others, often do not reflect accurate function of thyroid hormone. This is often due to feedback loops between cellular function and the Pituitary gland. Some of the regular hallmarks of hypothyroidism are poor energy, weight gain, poor sleep, hair thinning, digestive dysfunction (constipation and also alternating loose stools), cold hands and feet and pain. Here's an old blog on thyroid and adrenalin issues.

Another assessment of thyroid function is the Achilles return reflex. When stimulating the myotactic reflex a hammer hits the Achilles tendon stimulating, the dorsi flexors or calf muscles. The response should be a quick return of the foot to it’s resting position but with low thyroid the foot returns slowly. Low thyroid output equals low ATP (Adenosine Tri Phosphate – the energy used by the mitochondria/cells). This low energy state does not allow for optimal contraction and relaxation. This is where we can see specific issues with NCF and NBF’s within the muscle spindle cell.

Muscle tendons and associated ligaments provide a feedback loop via the Golgi Tendon Organs or GTO’s. There’s potential for pre-existing GTO dysfunction to drive muscle dysfunction and vice versa. As far back as the 1960s symptoms associated with muscle disorder from low thyroid were.

* Weakness

* Cramps pain and stiffness

* Hypertrophy

* Myotonoid features.

A well-documented feature of hypothyroidism is muscular hypertrophied calf muscles and despite their size may often test weak to stimulation.

Muscle pain, may indeed not be muscle related, it may be due to many factors, suggested above and these may even be related to hormones and neurotransmitters. Many people often deal with muscle aches and pains by constantly focusing on mobility work but these structures continually return to their pre mobility work status (although this could also be an underlying stability issue). In reality there can be many factors that create dysfunction such as crude touch, vibration, nociception, Golgi, Pacini-pressure related structures and many more. But even after seeing a skilled therapist, these still don’t appear to get better, then addressing the chemical aspects of pain and function might be the next sensible thing to do.

References:

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

Ramsay I. Thyroid disease and Muscle Dysfunction. William Heinemann Medical Books. 1974.

Purves, D. et al. Medical Neuroscience. 5th Edition. Sinauer Assocates Inc. 2001

Starr, M Hypothyroidism Type II. Mark Starr Trust 2013.

http://raypeat.com/articles/articles/hypothyroidism.shtml