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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

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.

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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