thyroid

Fasting and calorific restriction- Increased longevity or just a slower death?

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Intermittent fasting and calorific restriction (CR) seem to be the Zeitgeist of today’s nutrition and wellness sphere and has comparisons with the raw green sludge breakfast smoothie and these approaches to health. CR is often being touted as health enhancing because of a premise that sounds something like this. You fast or eat less than X calories and that has the capacity to slow down metabolism, ensuring that you produce less oxidative stress, autophagy ensues, and this opens up your 8th chakra ready for your beyond meat whopper. It’s true that fasting and CR can probably enhance your health when you are prone to over eating, and beyond that nothing else. Yes you will lose weight (seen as that’s the only variable that many people care about these days), but that result is down to one key fact. You are in a calorie deficit. Can you rebound from that restriction is the question that most need to evaluate.

CR and fasting promotes improvements to health and extending lifespan but the main reasons that it promotes longevity is probably for several reasons that include.

1. The restriction of polyunsaturated fats or PUFA.

2. The restriction of methionine, cysteine and sometimes tryptophan.

3. Perhaps less consumption of pesticides and metals.

The question of do you need to fast, should be rephrased with do you even need to fast? What about addressing what can extend lifespan and still maintain an optimal level of metabolism?

PUFA and mitochondrial uncoupling

Let’s start with PUFA which are commonly known as vegetable, seed, fish, soy and other oils, including olive oil (which is the better of the lot and when used cold has some useful qualities). The other oils share similarities, as they are all unstable especially so when heated. The most unstable oils in general use and over recommended are the omega 3’s particularly DHA and EPA. I’ve recently seen so called holistic practitioners recommending in excess of 6 grams of DHA to improve anti-inflammatory responses and so-called membrane fluidity. One of the key problems with this approach is that increased DHA levels are known to occur in the obese and diabetics (Madison Sullivan et al., 2018) and this increase is associated with reduced mitochondrial enzymes (metabolic enhancers).

 

PUFAs like DHA are often touted as protective because they induce a process called mitochondrial uncoupling. This can occur when your’e cold, when you don’t produce enough thyroid hormone and other stressors. It can indeed be protective but DHA for example creates something called proton leak within the cells, and decreases the efficiency of the cell. Oxygen efficiency is lost and production of energy or adenosine triphosphate (ATP) is also wasteful. This sits well with many who promote theoretical mechanisms of longevity such as the rate of living theory (Speakman et al., 2004) (Vaanholt, Daan, Schubert, & Visser, 2009) and the membrane pacemaker theory (Hulbert, 2007; Hulbert, Kelly, & Abbott, 2014). A. J Hulbert is a well-respected thyroid researcher who completed a large body of work on the role of thyroid hormones and fatty acids and their role in ‘membrane fluidity’. Interestingly Hulbert proposes that mammals and birds with a high metabolic rate (much like Elie Metchnikoff’s theories that link low gut bacteria with metabolism in birds, mammals and longevity) and increased longevity often have this key feature in common. They generally have low saturation of PUFAs as determined by something called the peroxidation index (PI). Conversely animals with high PUFA and PI have decreased longevity, but the membrane pacemaker theory postulates it as high metabolic rate, inducing uncoupling and characterized by increased reaction oxygen species (ROS) and the production of superoxide and superoxide dismutase (SOD).

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“There’s an inverse relationship between the peroxidation index of skeletal muscle phospholipids and maximum lifespan of mammal and bird species of different sizes.” A.J.Hulbert

 

 This forms a major component of the rate of living theory or that increased metabolism generates ROS ergo slowing metabolism down, produces less ROS and that’s productive. Although it’s not and this is where many people get confused about efficient thyroid function, enhanced metabolism and potential oxidative stress. I was reminded by a Ray Peat Newsletter earlier on the year how SOD remains elevated throughout the lifespan of those with Down syndrome and that serotonin increases SOD, contributing to decreased longevity. With excess PUFA consumption and tissue saturation, SOD increases as does uncoupling, lipid peroxidation and high levels of malondialdehyde (MDA) are observed with excess lipid peroxidation (Chen & Li, 2016). SOD can be counteracted by glutathione (SOD/G ratio) but this diminishes over time. This enhances the reductive state and perpetuates the gain of electrons, which are a hallmark of damaged physiology and shift efficient energy production away from oxidative metabolism of glucose and metabolic inflexibility.

 

PUFA, like DHA does initiate mitochondrial uncoupling but it’s inefficient and increases SOD degrading aerobic metabolism, which comes at a cost to lifespan. Hulbert notes that a 24% decrease in PI, is associated with doubling of lifespan and that calorific restriction alters the acyl composition of the cell membrane. Why?  Because PUFA are removed from the cell membrane to be used as fuel. Again this can be problematic if you persistently use unsaturated fatty acids as fuel. Not to mention that refeeding fasted subjects and those on a ketogenic diet are well known to depress thyroid hormone responsiveness, thyroid hormone receptors and glucose tolerance(Boelen, Wiersinga, & Fliers, 2008)(Garbow et al., 2011)(Kose, Guzel, Demir, & Arslan, 2017). Yes there are indeed many short-term studies showing positive changes from CR and ketogenic dieting. If one can benefit from these modalities great but if not metabolically flexible, it isn’t always going to be as fruitful as you think. It’s often these interactions that muddy the water between carbohydrate restriction and beneficial results. Hint, it’s never usually the carbohydrate, and if you’ve been prone to over eating, then that calorie deficit is always going to show a temporary positive effect.

If you’re someone that has tried many different interventions for improved health or even body composition and failed to get the results that you need, then the body requires a level playing field of energy and nutrients to create balance. Further stress from skipping meals, long hours without eating and failure to meet metabolic demands are some of the reasons why many develop metabolic inflexibility. The more stressed your physiology, the more prone it is to activating stress pathways and suppressing thyroid hormone, decreasing insulin responses and creating inflammation. More often than not those with tis existing inflexibility may not benefit from increased fatty acid oxidation mediated by a lack of available glucose.

Thyroid, PUFA and membrane composition and fluidity

My understanding of the so-called membrane, membrane pump theory and even membrane fluidity is certainly not of an expert but If I’m wrong here, I’m certainly willing to throw my hands up on in the air and say – I told you I wasn’t an expert.  I am reasonably sure of the interactions of thyroid hormone, its generality, it’s actions, organizational qualities and much like the theories of low serotonin, low estrogen, high cholesterol treated by statins, and that glyphosphate is a safe and friendly compound, that people with vested interests promote otherwise. I’m not going to go into the complexities of Gilbert Ling’s work (Gilbert N. Ling, 1965 1997, 2014) I’d be lying if I said I truly understand it but my attempt to summarize such a vast body of work.

The membrane pump theory has been a widely accepted unproven theory that appears on paper, to be unable energetically to support and each pump requiring unaccountable levels of ATP. Ling’s work suggests that membrane interactions are largely supported by organised or structured water interfaces and that there is no cellular membrane to speak of. Thyroid hormone, proteins and cholesterol are other integral components of this interface.

It’s always contentious when someone ends up disproving a theory that’s widely accepted without being proven.

Does it make sense that during fasting, these essential PUFA’s are depleted from this so-called membrane and replaced with cholesterol? Can they really be that essential? Thyroid hormones have been shown to modify this “membrane permeability”, cooperatively influencing behavior of enzymes and can penetrate the phospholipid bilayers  (Issé, Yunes Quartino, Fidelio, & Farías, 2013). Triiodothyronine or T3 appears similar to cholesterol’s action, increasing fluidity in ordered gel phases and decreasing in liquid crystalline states of phospholipids. I’m guessing that alterations in structured water through positive/ negative charges, and interactions between organisational qualities of thyroid hormones and cholesterol could be the ideal interface. This may explain why in hypothyroidism the so-called membrane, becomes more disorganised, less gel like and more abundant in PUFA (PUFAs degrade cholesterol).

 Restriction of PUFA, methionine and other agents which reduce biology need to be compared with so called decreased rate of living theories to ascertain what really increases longevity. If we keep looking at theories that promote decreased function instead of maintaining and improving order. The end result may be decreased lifespan and a slow death of cellular function.

 

References:

Boelen, A., Wiersinga, W. M., & Fliers, E. (2008). Fasting-Induced Changes in the Hypothalamus–Pituitary–Thyroid Axis. Thyroid, 18, 12–129. https://doi.org/10.1089/thy.2007.0253

Chen, Y., & Li, P. (2016). Fatty acid metabolism and cancer development. Science Bulletin, 61(19), 1473–1479. https://doi.org/10.1007/S11434-016-1129-4

Garbow, J. R., Doherty, J. M., Schugar, R. C., Travers, S., Weber, M. L., Wentz, A. E., … Crawford, P. A. (2011). Hepatic steatosis, inflammation, and ER stress in mice maintained long term on a very low-carbohydrate ketogenic diet. American Journal of Physiology - Gastrointestinal and Liver Physiology. https://doi.org/10.1152/ajpgi.00539.2010

Hulbert, A. J. (2007). Membrane fatty acids as pacemakers of animal metabolism. In Lipids. https://doi.org/10.1007/s11745-007-3058-0

Hulbert, A. J., Kelly, M. A., & Abbott, S. K. (2014). Polyunsaturated fats, membrane lipids and animal longevity. Journal of Comparative Physiology B: Biochemical, Systemic, and Environmental Physiology. https://doi.org/10.1007/s00360-013-0786-8

Issé, B. A., Yunes Quartino, P., Fidelio, G. D., & Farías, R. N. (2013). Thyroid hormones-membrane interaction: Reversible association of hormones with organized phospholipids with changes in fluidity and dipole potential. Chemistry and Physics of Lipids. https://doi.org/10.1016/j.chemphyslip.2013.08.007

Kose, E., Guzel, O., Demir, K., & Arslan, N. (2017). Changes of thyroid hormonal status in patients receiving ketogenic diet due to intractable epilepsy. Journal of Pediatric Endocrinology and Metabolism. https://doi.org/10.1515/jpem-2016-0281

Ling, Gilbert N. (1997). Debunking the Alleged Resurrection of the Sodium Pump Hypothesis. Physiological Chemistry and Physics and Medical NMR.

Ling, Gilbert N. (2014). Canwe see living structure in a cell? Physiological Chemistry and Physics and Medical NMR.

Ling, Gilbert Ning. (1965). THE PHYSICAL STATE OF WATER IN LIVING CELL AND MODEL SYSTEMS. Annals of the New York Academy of Sciences. https://doi.org/10.1111/j.1749-6632.1965.tb45406.x

Madison Sullivan, E., Pennington, E. R., Sparagna, G. C., Torres, M. J., Darrell Neufer, P., Harris, M., … Shaikh, S. R. (2018). Docosahexaenoic acid lowers cardiac mitochondrial enzyme activity by replacing linoleic acid in the phospholipidome. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.M117.812834

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

Vaanholt, L. M., Daan, S., Schubert, K. A., & Visser, G. H. (2009). Metabolism and Aging: Effects of Cold Exposure on Metabolic Rate, Body Composition, and Longevity in Mice. Physiological and Biochemical Zoology. https://doi.org/10.1086/589727

http://raypeat.com/articles/

http://www.gilbertling.org/

 

Improving brain health - amyloid, tau, and energy

Neurological and neurocognitive diseases have often been associated with the peptide amyloid beta (AB) and considered a main culprit in the onset of Alzheimer’s disease (AD) due to its elevations in the central nervous system (CNS) or brain. Initial ideas behind AB accumulation were derived from Dr Alois Alzheimer’s observations in 1906 that peptide deposits, entangled structures and plaques were present in a patient with severe neurological and neurocognitive function. Much of the research over the last three decades has focused on AB which has two pathways, non amyloidogenic forming 3 soluble fragments and the amyloidogenic pathway providing the AB associated with AD (Gosztyla, Brothers, & Robinson, 2018).

The Verve - The Drugs Don't Work

The drugs don’t work they just make you worse but I know I’ll see your face again.

Despite many promising drugs, interventions ( y secretase inhibitors) focusing on lowering AB have been found to worsen cognitive function and increase susceptibility to infection (Penninkilampi, Brothers, & Eslick, 2016). Estrogen has often been touted as a protective hormone against both cardiovascular disease and cancers despite large bodies of conflicting and unsupportive data (Derwahl & Nicula, 2014)(Felty & Roy, 2005) (Benjamin, Toles, Seltzer, & Deutsch, 1993). In the last ten years or so further confusion has been added to most people’s (including doctors) understanding of  estrogen and its so called protective mechanisms. In AD and dementia studies, estrogen was shown to decrease AB production, therefore it must be protective. The only downside to this observation is that it decreased AB, worsened cognition and increased susceptibility to infections (Gosztyla et al., 2018).

These observations tie in well to the current hypothesis that AB is found in most life forms, is protective, and increases as a form of anti-microbial action against certain agents such as viral and bacterial. Another interesting observation is the comparison between the actions of estrogen and progesterone in AD and dementia. Estrogen lowers AB but progesterone does not. Progesterone also decreases another key component of AD,  a structure in the CNS called tau. Tau is a neuronal microtubule associated protein and a structural factor within the brain, which major functions are the promotion of self assembly and tau stabilisation (Carroll et al., 2007). The commonality of AD and dementia like states is tau aggregation and can be elevated in AD and also  traumatic brain injury (TBI). Progesterone not only decreases damaged/entangled (hyperphosphorylated) tau it’s shown to be protective in TBI cases.

Increased estrogen is associated with increased excitability, seizures and neuronal degradation and this appears elevated in the premenstrual and estrous phases (Broestl et al., 2018). With increased aspects of pollution such as aluminium, mercury and cadmium and air and water borne pollutants that mimic estrogen, the potential of increased neurological damage is at an all-time high (Exley, 2013) (Annamalai & Namasivayam, 2015). Perhaps instrumental in the incidence and prevalence of neurological disease in the industrialised world?

Dietary fats, glucose and thyroid.

There’s far too much resistance in medicine to consider both neurological decline and diseases such as cancer as issues of metabolism. Mutations occur when biology degrades, when the mitochondrial aerobic function is compromised and there’s much that can be done to improve that area of function. The insistence that unsaturated fat is protective to neuronal structures appears problematic. In Parkinson’s disease for example degradation of polyunsaturated fats (both n3s and n6s) appears to increase lipid peroxidation, neuronal damage and that maintaining cholesterol levels appears to be protective (Alecu & Bennett, 2019). A common theme between all the neurological and oncological diseases is an abundance of PUFA and their oxidation, decreased glucose efficiency, decreased thyroid availability and mitochondrial damage(Schönfeld & Reiser, 2013)(Choi et al., 2017)

Some of the conflicts between the connection of low thyroid function and decreased neurological function are grounded in the persistence that biochemical evaluation of TSH and thyroid hormones  (FT4 and FT3) are reliable and indicators of tissue saturation both in the hypothalamus, pituitary, neuronal and other tissues. Given the vast aspects of organisation allowed by adequate thyroid hormone and its effects on metabolism, movement, digestion, temperature, pulse rate, sleep, blood sugar, cholesterol and blood pressure, these variations might be of more value than reliance on poorly defined blood tests.

Endotoxin, gut and blood brain barrier.

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Chronic digestive stress increases endotoxin, serotonin and histamine and can cross the blood brain barrier

 

Intestinal hyperpermeability or leaky gut syndrome has been very fashionable for the last ten years and holistic narratives of detoxing, raw green foods and probiotics seems to still be the Zeitgeist. Endotoxin or LPS (lipopolysaccharides) are well known to induce stress responses, stimulating the production of both serotonin and histamine and adrenal pathways. Histamine and serotonin can increase the permeability of the blood brain barrier to  endotoxin induced increases of damaged tau structures is another aspect of neurological degradation(Wang et al., 2018). It also increases AB but know we have an idea that increasing AB is protective and it’s progression to plaques might be problematic. Attempting to lower AB is a reductionism that should best be avoided.

The concepts of detoxing and fasting might temporarily decrease endotoxin but they also have the capacity to make you colder, metabolically less efficient, decrease liver efficiency and lower thyroid hormone responsiveness that does not automatically increase after re-feeding (Boelen, Wiersinga, & Fliers, 2008). Ensuring adequate energy availability, endotoxin reducing foods like orange juice, carrots (Peat, 1997) (Ghanim et al., 2010) (Babic, Nguyen‐the, Amiot, & Aubert, 1994), and promoting restoring oxidative metabolism with compounds like methylene blue and caffeine (Eskelinen & Kivipelto, 2010)(Berrocal, Caballero-Bermejo, Gutierrez-Merino, & Mata, 2019), moderate exercise, engaging in life affirming activities and light exposure might be the some of the most effective factors in the fight against neurological disease.


References:

Alecu, I., & Bennett, S. A. L. (2019). Dysregulated lipid metabolism and its role in α-synucleinopathy in Parkinson’s disease. Frontiers in Neuroscience. https://doi.org/10.3389/fnins.2019.00328

Annamalai, J., & Namasivayam, V. (2015). Endocrine disrupting chemicals in the atmosphere: Their effects on humans and wildlife. Environment International. https://doi.org/10.1016/j.envint.2014.12.006

Babic, I., Nguyen‐the, C., Amiot, M. J., & Aubert, S. (1994). Antimicrobial activity of shredded carrot extracts on food‐borne bacteria and yeast. Journal of Applied Bacteriology. https://doi.org/10.1111/j.1365-2672.1994.tb01608.x

Benjamin, F., Toles, A. W., Seltzer, V. L., & Deutsch, S. (1993). Excessive estradiol secretion in polycystic ovarian disease. American Journal of Obstetrics and Gynecology, 169(5), 1223–1226. https://doi.org/10.1016/0002-9378(93)90286-R

Berrocal, M., Caballero-Bermejo, M., Gutierrez-Merino, C., & Mata, A. M. (2019). Methylene Blue Blocks and Reverses the Inhibitory Effect of Tau on PMCA Function. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms20143521

Boelen, A., Wiersinga, W. M., & Fliers, E. (2008). Fasting-Induced Changes in the Hypothalamus–Pituitary–Thyroid Axis. Thyroid, 18, 12–129. https://doi.org/10.1089/thy.2007.0253

Broestl, L., Worden, K., Moreno, A. J., Davis, E. J., Wang, D., Garay, B., … Dubal, D. B. (2018). Ovarian cycle stages modulate alzheimer-related cognitive and brain network alterations in female mice. ENeuro. https://doi.org/10.1523/ENEURO.0132-17.2018

Carroll, J. C., Rosario, E. R., Chang, L., Stanczyk, F. Z., Oddo, S., LaFerla, F. M., & Pike, C. J. (2007). Progesterone and estrogen regulate Alzheimer-like neuropathology in female 3xTg-AD mice. Journal of Neuroscience. https://doi.org/10.1523/JNEUROSCI.2718-07.2007

Choi, H. J., Byun, M. S., Yi, D., Sohn, B. K., Lee, J. H., Lee, J. Y., … Lee, D. Y. (2017). Associations of thyroid hormone serum levels with in-vivo Alzheimer’s disease pathologies. Alzheimer’s Research and Therapy. https://doi.org/10.1186/s13195-017-0291-5

 Derwahl, M., & Nicula, D. (2014). Estrogen and its role in thyroid cancer. Endocrine-Related Cancer. https://doi.org/10.1530/ERC-14-0053

Eskelinen, M. H., & Kivipelto, M. (2010). Caffeine as a protective factor in dementia and Alzheimer’s disease. In Journal of Alzheimer’s Disease (Vol. 20). https://doi.org/10.3233/JAD-2010-1404

Exley, C. (2013). Human exposure to aluminium. Environmental Sciences: Processes and Impacts. https://doi.org/10.1039/c3em00374d

Felty, Q., & Roy, D. (2005). Estrogen, mitochondria, and growth of cancer and non-cancer cells. Journal of Carcinogenesis. https://doi.org/10.1186/1477-3163-4-1

Ghanim, H., Sia, C. L., Upadhyay, M., Korzeniewski, K., Viswanathan, P., Abuaysheh, S., … Dandona, P. (2010). Orange juice neutralizes the proinflammatory effect of a high-fat, high-carbohydrate meal and prevents endotoxin increase and toll-like receptor expression. American Journal of Clinical Nutrition. https://doi.org/10.3945/ajcn.2009.28584

Gosztyla, M. L., Brothers, H. M., & Robinson, S. R. (2018). Alzheimer’s Amyloid-β is an Antimicrobial Peptide: A Review of the Evidence. Journal of Alzheimer’s Disease. https://doi.org/10.3233/JAD-171133

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

Penninkilampi, R., Brothers, H. M., & Eslick, G. D. (2016). Pharmacological Agents Targeting γ-Secretase Increase Risk of Cancer and Cognitive Decline in Alzheimer’s Disease Patients: A Systematic Review and Meta-Analysis. Journal of Alzheimer’s Disease. https://doi.org/10.3233/JAD-160275

Schönfeld, P., & Reiser, G. (2013). Why does Brain Metabolism not Favor Burning of Fatty Acids to Provide Energy? - Reflections on Disadvantages of the Use of Free Fatty Acids as Fuel for Brain. Journal of Cerebral Blood Flow & Metabolism. https://doi.org/10.1038/jcbfm.2013.128

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). https://doi.org/10.1371/journal.pone.0114455

Wang, L.-M., Wu, Q., Kirk, R. A., Horn, K. P., Ebada Salem, A. H., Hoffman, J. M., … Morton, K. A. (2018). Lipopolysaccharide endotoxemia induces amyloid-β and p-tau formation in the rat brain. American Journal of Nuclear Medicine and Molecular Imaging.

 

Why Veganism won’t save the planet

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If you’re influenced by the left to save the planet, a plant-based diet strategy has been suggested as a factor in saving us from ecological ruin. From the right, the blind faith in technological advances that may or may not come but as long as we make as much cash in the mean-time who cares. From an environmental standpoint the concept of a plant-based diet has many factors that on paper appear useful but under scrutiny don’t add up. One of the reasons, in my opinion is that methane, is not as significant factor in global emissions compared to the effects of pollution and health and switching to a plant-based diet will not improve health or ecological interaction by any significant means.

Global methane emissions and mitigation opportunities suggest that global methane emissions will rise 15% from approximately 6875 million metric tons of CO2 to the equivalent of 8904 MMTCO2 by 2020. Their chart above (although almost a decade old is open to revision and critique) highlights the sources and notes that the most prominent source (29%) is derived from enteric fermentation, or cows’ farts to you and me.

Global methane emissions and mitigation opportunities suggest that global methane emissions will rise 15% from approximately 6875 million metric tons of CO2 to the equivalent of 8904 MMTCO2 by 2020. Their chart above (although almost a decade old is open to revision and critique) highlights the sources and notes that the most prominent source (29%) is derived from enteric fermentation, or cows’ farts to you and me.

If you take a look at the combined total of other sources of methane such as rice farming (10%) landfills (11%) and other agricultural sources (7%) , that makes a total combined total of 28%, if cow farts decrease because we all go vegan, you can rest assured that a) landfill will continue to increase and b) vegetables, rice, beans  and other sources of agricultural methane levels will keep increasing  as replacement meat and dairy food sources are needed.  Land fill from both food and other consumer waste is bound to increase as us humans are still not adjusted for life beyond consumerism and waste. A factor hammered home with each new phone, beauty or unnecessary hygiene product.

It’s not a trivial point suggesting that the requirements of meeting nutritional needs by increasing plant-based nutrition, will increase both CO2 and methane levels. But hey less cows fart must mean less methane. I’ve rarely seen anyone who recommends the decreasing meat/increased plant-based approach discuss the devastating ecological effects that is a side effect of growing vast amounts of crops in monoculture. Palm Oil is a useful description of what happens globally when crops are grown in monoculture, designed for industrial profits. This philosophy decimates indigenous wildlife, often increases pesticide use (and accumulation in human tissue) reshapes land and does nothing to address the over farming phenomena that depletes soil of essential nutrients.

The transfer and haulage of a predominantly plant-based diet still requires the standard means of transport of all food stuffs. Clearly industrial pollution, combustion engines and fuels are the real elephant in the room? Contributing to an increase in disease globally through airborne pollution, which runs into many millions each year. Poly cyclic aromatic hydrocarbons and other fine particulate matter are contributing to increased emissions and pollutants that are doing more to the environment and health, yet the focus is still predominantly on cow’s farts.

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The Prolongation of Life.

Elie. Metchnikoff whose work on digestion earned hime the Noble science prize showed that exclusive diets such as purely plant based or meat had increased intestinal putrefaction and disease compared to species that ate a varied diet. Most animals that rely on plants and grasses fail to achieve longevity of other species (However outliers are elephants - 60 years or so and giant tortoises 150 years or so but known to eat fruit.


If these decisions were philosophical, I can understand the vegan’s plight to a degree. Industrialised farming is a problem, animal welfare in prison like  cow sheds are problematic. Animals that aren’t raised in normal habitats is an issue. Raising stressed animals creates less nutritious meats. So shouldn’t we be considering devolving industrialised farming practices that are designed to line large corporations’ pockets with no disregard to animal welfare or quality of the nutrition that is provided. There are many factors that influence meat quality and health (3). Surely if we integrated farming practices in line with aspects of permaculture, waste is decreased, local community needs are met and the need for transporting large distances reduces environmental impact is also reduced.  

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“The illusion of unlimited powers, nourished by astonishing scientific and technological achievements, has produced the concurrent illusion of having solved the problem of production. The latter illusion is based on the failure to distinguish between income and capital where this distinction matters most. Every economist and businessman is familiar with the distinction and applies it conscientiously and with considerable subtlety to all economic affairs – except where it really matters: namely, the irreplaceable capital which man has not made, but simply found, and without which he can do nothing.”

Is eating other organisms really an unhealthy practice? I see on a daily basis birds plucking dragonflies out the air, crows eating other birds remains, cat’s eating birds, geckos eating ants and a whole manner of carnivore behaviour. From an evolutionary perspective this practice in part played a role in our development as conscious beings. One theory of evolutionary enhancements might be the increased consumption of thyroid rich tissues.

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Thyroid hormone and increased central nervous system capacity?

For me the philosophical points of veganism have some merit, but the practice ignores millennia of evolution and nature as a whole, it’s just another reductionism that’s poorly thought through with limited outcomes. We should strive for better animal welfare and that means taking a more rounded view of what’s broken. This blog isn’t dealing with all of the exhaustive factors involved with what’s problematic (and even the larger concepts and theories at work such as the Vernadsky view of biosphere and self regulating processes), such as over-production and wastefulness but from a nutrition perspective, I’ve worked with and met too many people, who over years have decided that meat eating was advantageous, compared to the knee jerk reactions of short term nutritional interventions.

References:

  1. Rhythms of Life: Thyroid Hormone & The Origin of Species. By Susan J Crockford. Victoria (Canada): Trafford Publishing. 2006.

  2. Metchnikoff, E. (1907) The prolongation of life: Optimistic studies. G. P. Putnam & Sons, London.

  3. http://raypeat.com/articles/articles/meat-physiology-stress.shtml

  4. Schumacher, E. F. (Ernst Friedrich), 1911-1977. Small Is Beautiful; Economics as If People Mattered.

Why fruit juice won’t give you cancer.

But it can protect you against it.

But it can protect you against it.

You may have noticed the carbohydrate fearing headline stating that - "One small glass of juice a day raises cancer risk, " yesterday. Do you know when you’ve been tangoed?

This is based upon the study by Chazelas et al (Chazelas et al 2019) and being used to justify the swathe of dogmatic headlines in the press.Apart from the study being based on food questionnaires (mean food log was 5.6 days over 5 years hardly conclusive) which are not reliable indicators of actual consumption, the authors suggest that the mechanisms that might drive the association are as follows.

1.    Excessive sugar consumption could contribute to obesity driven mechanisms. There's no doubt that excess carbohydrate, fat and protein contribute to obesity when an EXCESS of calories are consumed (and the other multifactorial issues associated with obesity.

2.    Sugar from juice contributes to increased glycaemic load and inflammation. This point doesn't add up because many fruit juices have a low glycaemic load, associated with anti- inflammatory responses (polyphenols, vitamin c, capacity to lower endotoxins, improve blood sugar regulation and cholesterol levels). Many grains have higher glycaemic loads and index than juices. So is this really a valid argument?

Of the 101, 000 or so participants the increased risk associated with sugary drinks was found in those who exercised less. In an important factor, if you combine over consumption and decreased activity. Another point that the authors suggest on sugary drinks is that additives to sweetened beverages like sodas could also contribute to risk. Indeed a valid point.

It starts with a hint of truth and a headline or meme tends to become written in folklore, the myth of the carbohydrate rich food churning out death in its path. These small, half or even quarter truths often disappear when you scratch beneath the surface. That’s why I actively encourage carbohydrate and specifically carbohydrate consumption in my programs. Even most people I have met rarely chug down large amounts of fruit juices in isolation and even if glycemic index\load were an issue, when you consume carbohydrate rich foods with proteins and fats, these concepts are somewhat irrelevant.

Orange juice (or any juices) is one of those foods that still seems to be getting a bad rap but many people who demean its nature often fail to look at the studies that have shown it to be protective. You might have heard...but the sugar levels or but it’s acidic. Just take a look at the tabloid’s permanent vilification of the simple juice drink, which is based on half-truths of small increased risk with limited data. To play devil’s advocate, there’s no doubting that some people with less money available have been seduced into purchasing more junk food. It’s cheap, it’s filling and it’s full of sugar, vegetable oils, preservatives, GMOs, fillers, emulsifiers, additives like flavouring, enhancers, gums and much more. Yet still, the sugar is the demon in this list. Not even the pollution that’s shown to increase cancer, heart diseases, diabetes and neurodegenerative diseases, it’s still sugar and even if you drink fruit juice, it’s the sugar that will kill you.

So, with that in mind let’s consider what a simple food like orange juice could do to hasten, I’m sorry I meant prevent neurological and metabolic decline. Let’s first add some context. It should be no surprise that if you just drink large amounts of juice on their own, without balancing their ability to enter the blood stream with fats and or proteins, it isn’t going to be as beneficial. This is also why throwing large amounts of sweetened fizzy drinks down one’s neck can be problematic. The Glycemic index becomes redundant when you add another food into the mix, therefore drinking fruit juices with fats and proteins helps to normalise blood sugar responses in isolation. So why orange juice? Here are just a couple of reasons

Orange juice decreases inflammation

Eating a variety of foods has the capacity to increase inflammatory and damaging agents like endotoxin. Endotoxin or lipopolysaccharides is well known to increase in high fat and carbohydrate meals, especially so when fibrous poorly digested foods are consumed. High fat diets also induce endotoxin, and this is well known to induce intestinal hyperpermeability or the more well-known leaky gut syndrome. Consumption of orange juice appears to significantly reduce the levels and effects of inflammation induced by endotoxin (Ghanim et al., 2010) . Unfortunately, many foods are often kept stable longer with additives like carrageenan and gums, which also promote increased endotoxin.

Orange juice attenuates metabolic dysfunction

 “ Despite media concern, daily orange juice consumption did not result in adverse metabolic effects, despite providing additional dietary sugars. Data from epidemiological and in vitro studies suggest that orange juice (OJ) may have a positive impact on lipid metabolism. “ (Simpson, Mendis, & Macdonald, 2016)

During times of stress, under eating or consuming foods low in carbohydrates the response is to liberate energy from stored fats in the form of triglycerides. As metabolism becomes compromised high levels of triglycerides are known to be present in blood sugar dysregulation. There’s much in the press to suggest that sugar from fruit juice consumption increases cardiac risk but there are many studies that suggest otherwise, with the observed effect being reduced triglycerides and cholesterol (Aptekmann & Cesar, 2013). The cardiac protective factors aren’t limited to orange juice alone, pomegranate and other juices also seem to offer similar results (Moazzen & Alizadeh, 2017)

Orange juice decreases carcinogen production

A very relevant and protective mechanism of orange juice (and others) and fruit peel consumption is the decreased risk of gastrointestinal cancers (Xu, Song, & Reed, 1993). Nitrates and nitrates are naturally occurring compounds found in a variety of foods. Nitrates are often used in preservatives and sodium nitrites are ubiquitous in preserved meats and have a significant relationship between cancers in many of the mucosal areas including the mouth, bowel and lungs.. Nitrates have been implicated in not just intestinal and stomach cancers but increasingly thyroid cancers (Hernández- Ramírez et al., 2009). This occurs through increases in N-nitroso compounds (NOC) which increase the capacity of cell mutation but there are extensive studies that show many classes of NOC inhibitors which include vitamin e and vitamin C that negate that risk.

Of course, for optimal effects, ensuring adequate protein and fats are consumed will always be beneficial. We’ve known that compromised blood sugar and insulin responses are rarely to do with consuming carbohydrates. Unless excessive eating and obesity are the association, there’s plenty more relevant relationships such as environmental pollutants and other stressors that show a clear effect on all aspects of metabolism and increased metabolic disease. Yet many people seem intent on shooting the messenger and vilifying protective carbohydrates such as fruit juice.

 

References: 

 1.    Aptekmann, N. P., & Cesar, T. B. (2013). Long-term orange juice consumption is associated with low LDL-cholesterol and apolipoprotein B in normal and moderately hypercholesterolemic subjects. Lipids in Health and Disease. https://doi.org/10.1186/1476-511X-12-119

2.   Chazelas Eloi, Srour Bernard, Desmetz Elisa, KesseGuyot Emmanuelle, Julia Chantal, Deschamps Valérie et al. Sugary drink consumption and risk of cancer: results from NutriNet-Santé prospective cohort BMJ2019; 366 :l2408

3.    Ghanim, H., Sia, C. L., Upadhyay, M., Korzeniewski, K., Viswanathan, P., Abuaysheh, S., … Dandona, P. (2010). Orange juice neutralizes the proinflammatory effect of a high-fat, high-carbohydrate meal and prevents endotoxin increase and toll-like receptor expression. American Journal of Clinical Nutrition. https://doi.org/10.3945/ajcn.2009.28584

4.    Hernández-Ramírez, R. U., Galván-Portillo, M. V., Ward, M. H., Agudo, A., González, C. A., Oñate-Ocaña, L. F., … López-Carrillo, L. (2009). Dietary intake of polyphenols, nitrate and nitrite and gastric cancer risk in Mexico City. International Journal of Cancer. https://doi.org/10.1002/ijc.24454

5.    Moazzen, H., & Alizadeh, M. (2017). Effects of Pomegranate Juice on Cardiovascular Risk Factors in Patients with Metabolic Syndrome: a Double-Blinded, Randomized Crossover Controlled Trial. Plant Foods for Human Nutrition. https://doi.org/10.1007/s11130-017-0605-6

6.    Simpson, E. J., Mendis, B., & Macdonald, I. A. (2016). Orange juice consumption and its effect on blood lipid profile and indices of the metabolic syndrome; A randomised, controlled trial in an at-risk population. Food and Function. https://doi.org/10.1039/c6fo00039h

7.    Xu, G. P., Song, P. J., & Reed, P. I. (1993). Effects of fruit juices, processed vegetable juice, orange peel and green tea on endogenous formation of N-nitrosoproline in subjects from a high-risk area for gastric cancer in Moping County, China. European Journal of Cancer Prevention. https://doi.org/10.1097/00008469-199307000-00007

 

 

Chronic stress, appetite suppression, control and metabolic inflexibility.

It was the famous stress scientist Hans Selye who suggested that stress can be a positive or negative force. But how do we know whether we are dealing with stress effectively? There’s a common theme among clients both male and female who have got used to feeling in control of their health by suppressing appetite, symptoms and a false sense of health by perhaps feeling in control. Is this control a false economy? A well-known symptom of stress is a loss of appetite and skipping breakfast, it feels better to perpetuate the production of stress hormones like adrenaline and cortisol to liberate energy from stored fats and stride through the day with their endorphin like qualities. A common theme of females suffering from poly cystic ovary syndrome (PCOS) is chronic irregular eating or over eating in the obese. High stress can be chronic and perceived as the norm. I’ve observed the former in my eldest daughter through under eating as a product of emotional stress

‘For those habituated to high levels of internal stress since early childhood, it is the absence of stress that creates unease, evoking boredom and a sense of meaningless. People may have become addicted to their own stress hormones, adrenaline and cortisol, Hans Selye observed. To such person’s stress feels desirable, while the absence of it feels like something to be avoided.’ Gabor Mate

It should come as no surprise why some studies suggest that short term fasting, and calorific restriction seem to be productive in reversing aspects of inflammation and auto immune disease. When the body is stressed even eating certain foods becomes stressful. Dairy, sugar, fruits, grains all get the blame. I feel better when I don’t eat these some say. I feel better when I don’t eat others say. Is it the food or is it you? Can you be so fragile that eating some fruit for example is enough to send your biology into a tail spin. Eating sugar in excess can be problematic but then so can eating fat or anything in excess.

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A foundation of good health is built upon biological flexibility, potential and far away from equilibrium states.

The inability to utilise carbohydrate is a snapshot of the inflexibility of an individuals’ metabolism and not the carbohydrate. Evolutionary biology has provided efficiency by aerobic metabolism of carbohydrate and fat. The loss of efficient use of carbohydrate/sugar is the hallmark of a loss of function or flexibility and the chronic use of fats as a fuel is problematic due to increased oxidation of these lipids which can damage the aerobic apparatus within the mitochondria. The Randle cycle or glucose fatty acid cycle should allow flexibility between using either fats or carbohydrate as a fuel (Randle, Garland, Hales, & Newsholme, 1963). It’s often the lack of flexibility, decreased oxidation of carbohydrate and perpetual use of fats that damage the energy producing cells. Saturated fats are the preferred fuel of aerobic (oxidative) metabolism but in aggressive metabolism of cancer cells, unsaturated fats are utilised perpetuating the damage, promoting inefficient glycolysis or anaerobic metabolism that creates the acidic state of the cell.

The dogma that persists in nutrition circles is not based on sound reasoning but limited ideas that look at short term studies related to carbohydrate restriction. When a system loses its capacity to regulate sugar, we blame sugar instead of looking at the variety of factors that are responsible for degraded biology, carbohydrate utilisation and insulin responses.

Whether excessive exercise or inadequate nutrition the end result may be similar and its effects are far reaching into metabolism, cardiovascular, sexual and reproductive physiology.

By improving life conditions (in many ways) the hormones of pleasure can have a bigger role in our physiology. I think the experience of pleasure (whatever capacity for pleasure there is) increases the ability to experience pleasure, but I don't offer this with much hope as a therapeutic approach, since I know of people who say that running to exhaustion makes them "feel good" - neither "feeling good" nor "having orgasms" has a clear meaning, at present. Ray Peat

I’m not suggesting that going long periods without eating are necessarily bad, nor if you enjoy running is that bad either. Context is key. If you enjoy running run. If you have the capacity to go long hours without eating, then do that too. However if you have a system that lacks flexibility these actions can be problematic.

Have you ever considered not engaging in intense exercise for a couple of weeks to see how your body really feels?

I think this is a useful test to discover where your biology is really at. It can help determine whether you have been propping up a dysfunctional biology with intense exercise that falsely elevates your body temperature through activation of the sympathetic stress pathway. Slowing down and just focusing on walking and a few stretches shouldn’t feel stressful. Equally an individual who switches to eating regularly every 3 hours or so with the same amount of calories they were previously eating shouldn’t feel stressful. We all have patterns, routines and to the extent that they are effective or not is dictated by the metabolic flexibility that one should have. I’ll also suggest that metabolic flexibility could be analogous to emotional flexibility and mood states. A sign of improvements to metabolic flexibility and flux is return of energy, ability to tolerate exercise, good sleep, libido and emotional responses among other aspects of function. How do you know if it’s working? This diagram suggests what drivers are necessary and how to overcome your unwanted symptoms with the right inputs.

Metabolic inflexibilitY.jpg

Some patience seeking the return of these aspects of function is needed. After all, if you have spent decades constrained by negative symptoms then it may take more than a few weeks or months to fully resolve these patterns. In addition to the foundational work on hormones and chemistry, some people might find a need to address belief systems or require counselling for trauma or emotional grief to help resolve emotional stressors.

 References

Mate, G. (2008). In the realm of hungry ghosts. Close encounters with addiction. Canadian Family Physician.

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. https://doi.org/10.1016/S0140-6736(63)91500-9

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

Selye, H. (1987). Stress without distress. In Society, stress, and disease, Vol. 5: Old age. (pp. 257–262). http://doi.org/10.1080/00228958.1983.10517713

 

Autoimmunity

Spring is here!.jpg

My previous motivation to write blogs was to inform everyone of all the things I knew, how I could help them and why I was probably correct with a healthy smattering of dogma. These days my motivation has changed and I suppose it goes with the old adage - The more you know, the less certain you become of a subject. Sometimes my purpose to write is to take what I have learnt or discovered and set it down for others to contest it, or to go back years later to compare current to previous writings and if my thoughts have stood the test of time.

 With auto immune disease (AI) protocols, I intend to discuss some of the problems associated with assuming that

a)    that the immune system has lost sense of self and is attacking itself at will.

b)    most of the foods suggested are optimal from an AI perspective

 For an example let’s take one of the most common AI diseases related to thyroid function such as Hashimoto’s which is the most common cause of hypothyroidism.

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‘Hashimoto/lymphocytic thyroiditis is an immunologic disorder in which lymphocytes become sensitised to thyroidal antigens and auto-antigen bodies are formed react with those antigens (Gardner et al., 2011).’

 Many recommend and invoke a drastic change to diet. The suggestion of an auto immune paleo type diet, which actually has some merit segmentally but perhaps loses sight of the main issues that drive an auto immune reaction. I’ll address the positives and negatives in the next blog but a common theme that dairy is problematic, and should be removed might better serve an individual if they were aware that it’s their stressed system that drives the response. Much like the assumptions that fruit should be restricted due to sugar content, which matches the dogma that sugar causes diabetes and removes key nutrients that enable efficient metabolism.

 So, on to what might be the most pertinent point of this post. A definition of an auto immune disease (AI) is the following:

 Auto-immune disease may result from the interaction of the genetic load of the individual, modification of self-tissue antigens by environmental agents such as virus or drugs and abnormalities of the immunological system itself such as the loss of controlling or suppressor T cells with age. In the majority of people the outcome is tolerance, maintenance of normal tissue architecture and function. In the unfortunate few the outcome is auto-immune disease, that is, failure to recognize ‘self’. (Panayi, 1976)

 This seems quite logical doesn’t it? The body must be attacking itself because it’s producing antibodies against its own tissues, a clear case of autoimmunity. Diagnosis of Hashimoto’s is usually based upon levels of the anti thyroid peroxidase (ATPO) and thyroglobulin antibodies (TgAb). The higher the levels the increased likelihood of autoimmunity. Increased and sustained antibodies must mean increased autoimmunity and the nefarious nature of attacking oneself.

However there are some that theorise a different view. Enter the Danger Theory proposed by Dr Polly Matzinger who suggests that the immune system is particularly good at recognising damaged and potentially dangerous tissue.

Invoking Occam’s razor and the simplest explanation seems the best choice, although the issues are just as complex. Using the example of the thyroid again as it’s the most common cancer diagnosed and susceptible to a number of insults namely pollution, stress, poor nutrition, preservatives like nitrates/nitrites and a significant factor is estrogen. Matzinger’s suggestions that heat shock proteins (HSP’s) could be at the heart of the AI response to a viral infection and increased temperatures. Estrogen’s actions would be slightly different but their action ultimately decreases body temperature by inhibition of thyroid function, inactivating enzymes, leading to unfolding of proteins.

Estrogen and disorganised tissue has long been implicated in cancer.  L.C. Strong who bred mice for genetic evaluation found back in the 1930’s the implications of estrogen and mutations.

Leonell Strong.png

Leonell C. Strong

‘“ The second contribution of genetics was the production and control of biological states that differed in cancer susceptibility and cancer resistance. This contribution made possible the discovery that the female hormone estrogen, was involved in the origin of several kinds of cancer in mice.”


AI disease is 80% more likely in females and estrogen can be considered a primary driver. Increasingly the role of environmental pollutants and their estrogen like effects have been implicated in diabetes, heart disease, thyroid dysfunction and fertility and AI disease doesn’t escape its noose (Gawda, Majka, Nowak, & Marcinkiewicz, 2017).

 In my recent Masters thesis I referenced that malondialdehyde (MDA) as suggested by others is a useful marker for determining the effects of stress on a system why?

 ‘Increased malondialdehyde (MDA) levels have been noted in overt and sub clinical hypothyroidism. As MDA levels reflect increased oxidation of lipids and may represent a suppression of CHO metabolism, this might be another useful marker for analysis when euthyroid serum values are recorded, yet hypothyroidism is suspected.

 Airborne pollutants create changes to reactive oxygen and reactive nitrogen species (RONS), which when increased, are pro-inflammatory and increase MDA via increased fat oxidation . Maybe the primary drivers behind AI action is part of the global response that decreases thyroid hormone communication, production and assimilation? An inability to regulate both blood sugar and utilise carbohydrate through the glucose-fatty acid/Randle cycle is a specific loss of function induced by pollution and thyroid inhibition. Thyroid is organisational, estrogen is a stimulator of growth and suppresses the organisational and protective actions of progesterone increasing growth and disorganisation (Peat 1992).

The strongest predictor for the development of the AI disease Lupus (SLE) is female sex with a female to male ratio of 9:1 (McMurray & May, 2003). Seems to be a pretty constant ratio with development of hypothyroid disease doesn’t it?

The markers below give a common overview of altered hormone levels shown in patients with Lupus. Once again the commonality of increased estrogen/estradiol and its stimulation of the pituitary hormone prolactin is observed. Suppression of the anabolic hormones and thyroid appears to be a key driver of the AI state.

Sex Hormone changes in auto immune disease (McMurray & May, 2003)

Sex Hormone changes in auto immune disease (McMurray & May, 2003)

In a previous blog, I suggested factors that could influence thyroid hormones and their appearance when tested. It might be normal for thyroid antibodies to persist being elevated for some time due to many factors which include use of T4 in isolation, excessive pollution, poor food choices, medical estrogens, lack of selenium and more. Again, blood tests may or may not offer a real time evaluation of thyroid status, which would be the main driver of resolving an AI state. Temperature and pulse rate to track thyroid hormone use and thyroid function at large is extremely useful. Maintaining energy, thyroid hormone and light exposure seems to be the most prudent action when it comes to having better conversations with the environment and what might a long term solution to resolving AI disease.

In part 2 I’ll elaborate on the problems associated with a reduced diet that promotes a decrease in function over time.

References:

  1. Gardner, D. G., Shoback, D. M., Greenspan, F. S. (Francis S., Beers, Mark H., ed.Berkow, Robert, ed. Bogin, Robert M., ed. Fletcher, Andrew J., ed. Merck Rahman, M. I. M. H. B. ; R. B., Schaffer, Alexander J.Avery, Mary Ellen Finberg, Laurence Markowitz, M., Ferrero, Narciso A., dir.Debaisi, Gustavo Ferrero, Fernando C. Gil, Stella Maris Mazzucchelli, María Teresa Nizzo, Dante D. Ossorio, María Fabiana Veber, S. E., … Hoskins, J. D. (2011). Greenspan’s Basic and Clinical Endocrinology. McGraw Hill.

  2. Gawda, A., Majka, G., Nowak, B., & Marcinkiewicz, J. (2017). Air pollution, oxidative stress, and exacerbation of autoimmune diseases. Central European Journal of Immunology. http://doi.org/10.5114/ceji.2017.70975

  3. Matzinger, P. (2012). The evolution of the danger theory. Expert Review of Clinical Immunology. http://doi.org/10.1586/eci.12.21

  4. McMurray, R. W., & May, W. (2003). Sex hormones and systemic lupus erythematosus: Review and meta-analysis. Arthritis and Rheumatism. http://doi.org/10.1002/art.11105

  5. Panayi, G. S. (1976). Auto-immune disease. Rheumatology. http://doi.org/10.1093/rheumatology/15.1.1

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

 

 



Sub Clinical Hypothyroidism

Strange, must-try exotic fruits!.jpg

I’ve seen a number of assumptions from doctors suggesting that there’s no optimal diet for improving thyroid function. If that were the case there would be no optimal diet for heart disease, cancer or autoimmune disease but there are many proposed guidelines of certain foods that should be avoided.

 If you want to slow down the thyroid eating plenty of cruciferous vegetables, fish oils and exposure to oestrogens (environmental pollution, contraception and other medical drugs) seems to inhibit thyroid function dramatically and large amounts of anti-thyroid (goitregens) foods are certainly linked with thyroid cancer. Often an individual’s perceived healthy choices can suppress thyroid function and therefore be resolved with nutrition alone. A functionally suppressed thyroid state that’s treated with thyroid hormone may not yield the best results.

 Sub clinical hypothyroidism (SCH) is an issue that divides endocrinology but when you look at the process of thyroid dysfunction there are some clear indicators that should suggest that it’s treatment would be the most sensible (but not the most money making) action in the long run. Let’s start with defining what SCH is.

SCH is usually defined as an asymptomatic state in which free T4 is normal but TSH (thyroid stimulating hormone or TSH is the pituitary stimulator of thyroid hormone) is elevated. If serum TSH is >10mU/L there is consensus that the patient should be treated with thyroxine because of the likelihood that the patient will develop overt hypothyroidism with subnormal T4 and because this degree of SCH predisposes to cardiovascular disease. When the TSH is in the range of 4.5 to 10 mU/L, there is controversy about the efficacy of T4 therapy (Lavin, N, Ali, Omar., Beall, M.U., Bhutto, 2016).

Although many people with most forms of thyroid disease often present with diverse symptoms due to the systemic effects of thyroid hormone action but are often ignored through reductionist observation. The table below lists most of the major actions of thyroid function and deficits created by a hypothyroid state.


Thyroid hormone is necessary for all aspects of organised biology.

Thyroid hormone is necessary for all aspects of organised biology.

Here’s a short history of some of the contrasting opinions on treating SCH. Biondi cites the original controversies of Wartofsky and Dickey (2005) who favoured a narrower TSH range (Wartofsky & Dickey, 2005), which was in contrast to the opposition to a lower TSH suggested by Surks et al. (2005) (Biondi, 2013).

 The latter authors stated ‘that there was little evidence supporting the treatment of SCH, citing a single small study by Kong et al. treating 40 women with SCH (Kong et al., 2002).  The main findings demonstrated that thyroxine treatment had no impact on lipids, energy expenditure, weight gain or composition despite decreases in TSH levels in the treatment group (8.0 +- 1.5 mU/L change from baseline -4.6 +-2.3 mU/mL compared to 7.3 +- 1.6  -1.7 +-2.0 mU/L in the placebo). However this study, perhaps like many others (Laurberg et al., 2011) (Surks et al., 2005), failed to assess the nutritional status of this small group of patients. For example, if calorific excess were present, these markers may show little change, as weight loss requires a calorie deficit.  Conversely if a patient were chronically undernourished through a low nutrient intake, attempting to enhance metabolic rate and weight loss with TH replacement may be negated when adrenaline, glucagon and cortisol are produced to regulate blood sugar levels.

 Problems associated with some of the smaller seemingly positive older studies, is often the lack of control groups for comparison. A smaller RCT (treatment n-22 control n-19) comparing treatment of subjects with biochemically euthyroid TFTs  yet clinical hypothyroidism with thyroxine, found the intervention no more successful than placebo (Pollock et al., 2001). Whilst the effect of placebo cannot be discounted, the study only focused on cognitive function and wellbeing, factors that are a limited component of thyroid function.  A friend of mine also pointed out that the use of T4 alone and female cohort with an increased weight some 20kgs over the control group are also problematic issues in studies like this.

 More studies trickle through that builds upon previous suggestions that measuring TSH is a poor way to accurately assess thyroid function, primarily due to the facts that stress, environmental pollutants and nutrition can cause biochemistry and in particular thyroid blood tests to present as normal. The problem with ignoring SCH is the following scenario.

 You have isolated or a number of hypothyroid symptoms such as weight gain, high blood pressure, high cholesterol, hair loss, fatigue, low libido, altered menstrual cycle, anxiety or depression, poor sleep, constipation, brain fog, inflammation of the brain, altered heart contraction, dry skin etc.

 Good news Mrs X you have normal thyroid function as your blood tests came back within the normal ranges. The symptom/s you have must be in your head. Here you have high blood pressure take this anti-hypertensive medication.

The pituitary should be considered a source of evaluation that could be useful but should be treated with suspicion. There are many factors that alter thyroid feedback which include the disparity between the enzymes in the pituitary (deioidinase 2 supports the conversion of thyroid hormone in the pituitary and can appear normal)  and other tissues, thyroid receptor and mitochondrial damage. Recent meta analysis and other studies support the role of treating SCH to prevent cardiovascular disease, high cholesterol, hypertension (Ochs et al., 2008)(van Tienhoven-Wind & Dullaart, 2015)(Udovcic, Pena, Patham, Tabatabai, & Kansara, 2017) (Sun et al., 2017) and there’s a strong possibility that hypothyroidism in the central nervous system in areas like the prefrontal cortex are associated with dementia and Alzheimer’s (Pasqualetti, Pagano, Rengo, Ferrara, & Monzani, 2015)(Davis et al., 2008).

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Temperature, pulse and symptoms can be a useful indicator of function when bloods appear to support the notion of sub clinical hypothyroidism

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 It’s worth suggesting that endocrinologists should be well aware of all of the factors that can create the perception of normal blood tests, especially when individual’s present with clinical findings of hypothyroidism as suggested above. My previous posts on assessing thyroid function through body temperature and Ray Peat’s well written post should also be considered an integral part of assessment of thyroid evaluation. The concept of SCH is really only related to the blood test, because the other findings should give the game away.  Treating SCH shouldn’t be problematic when a thorough understanding of nutrition and environmental stimulus are known, and the only people at risk from taking a gradually increased dose of thryroxine would be individuals at risk of an immediate heart attack who generally would  present with a certain set of symptoms.

If Broda Barnes, an MD in the last century found that his patients didn’t succumb to heart disease when taking thyroid hormone. Shouldn’t we be looking for the more global implications of health improvements? Rather than treat high cholesterol, blood pressure, blood sugar, menstrual irregularities, metabolic syndrome (and many others) which all have a substantial relationship with thyroid function, with many studies that show substantial improvements when treated with thyroxine. Call me a cynic but perhaps a more detailed understanding of nutrition, environmental pollutants and their effects on thyroid physiology is probably more challenging to integrate into practice than completing genetic analysis with the proposed mutation driving a specific dysfunction.

 

References: 

BARNES, B. O. (1973). On the Genesis of Atherosclerosis. Journal of the American Geriatrics Society. http://doi.org/10.1111/j.1532-5415.1973.tb01239.x

Biondi, B. (2013). The normal TSH reference range: What has changed in the last decade? Journal of Clinical Endocrinology and Metabolism. http://doi.org/10.1210/jc.2013-2760

Davis, J. D., Podolanczuk, A., Donahue, J. E., Stopa, E., Hennessey, J. V, Luo, L. G., … Stern, R. A. (2008). Thyroid hormone levels in the prefrontal cortex of post-mortem brains of Alzheimer’s disease patients. Curr Aging Sci.

Kong, W. M., Sheikh, M. H., Lumb, P. J., Freedman, D. B., Crook, M., Doré, C. J., & Finer, N. (2002). A 6-month randomized trial of thyroxine treatment in women with mild subclinical hypothyroidism. American Journal of Medicine. http://doi.org/10.1016/S0002-9343(02)01022-7

Laurberg, P., Andersen, S., Carlé, A., Karmisholt, J., Knudsen, N., & Pedersen, I. B. (2011). The TSH upper reference limit: where are we at? Nature Reviews Endocrinology, 7(4), 232–239. http://doi.org/10.1038/nrendo.2011.13

Lavin, N, Ali, Omar., Beall, M.U., Bhutto, A. et al. (2016). Manual of Endocrinology and Metabolism (4th Editio). Lippincott Williams and Wilkins.

Ochs, N., Auer, R., Bauer, D. C., Nanchen, D., Gussekloo, J., Cornuz, J., & Rodondi, N. (2008). Meta-analysis: subclinical thyroid dysfunction and the risk for coronary heart disease and mortality. Annals of Internal Medicine, 148(11), 832–845.

Pasqualetti, G., Pagano, G., Rengo, G., Ferrara, N., & Monzani, F. (2015). Subclinical Hypothyroidism and Cognitive Impairment: Systematic Review and Meta-Analysis. The Journal of Clinical Endocrinology & Metabolism, 100(11), 4240–4248. http://doi.org/10.1210/jc.2015-2046

Pollock, M. A., Sturrock, A., Marshall, K., Davidson, K. M., Kelly, C. J., McMahon, A. D., & McLaren, E. H. (2001). Thyroxine treatment in patients with symptoms of hypothyroidism but thyroid function tests within the reference range: randomised double blind placebo controlled crossover trial. BMJ (Clinical Research Ed.). http://doi.org/10.1371/journal.pone.0098254

Sun, J., Yao, L., Fang, Y., Yang, R., Chen, Y., Yang, K., & Limin, T. (2017). The relationship between subclinical thyroid dysfunction and the risk of cardiovascular outcomes: a systematic review and meta-analysis of prospective cohort studies. International Journal of Endocrinology, 2017(2017). http://doi.org/10.1007/s00774-017-0828-5

Surks, M. I., Goswami, G., & Daniels, G. H. (2005). The thyrotropin reference range should remain unchanged. Journal of Clinical Endocrinology and Metabolism, 90(9), 5489–5496. http://doi.org/10.1210/jc.2005-0170

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

van Tienhoven-Wind, L. J. N., & Dullaart, R. P. F. (2015). Low-normal thyroid function and the pathogenesis of common cardio-metabolic disorders. European Journal of Clinical Investigation. http://doi.org/10.1111/eci.12423

Wartofsky, L., & Dickey, R. A. (2005). The evidence for a narrower thyrotropin reference range is compelling. Journal of Clinical Endocrinology and Metabolism. http://doi.org/10.1210/jc.2005-0455

Body temperature and health

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

 

·      Good energy

·      Good Digestion 2-3 bowel movements per day

·      Restorative sleep

·      Balanced mood free of depression or anxiety

·      Desire for life, motivation, hobbies and interests

·      Healthy libido

·      Absence of pain

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

What does your body temperature suggest about your health?

Get cold…read on

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

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

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

Thyroid hormone affects all aspects of biology

 

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

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

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

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

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

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

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

 

References:

 

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

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

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

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

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

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

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

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

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

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

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

 

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 through 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?

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

Being holistic versus (holistic) critical thinking.

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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

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.

Resolving digestion issues, rarely involves the need for expensive testing.

Resolving digestion issues, rarely involves the need for expensive testing.

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

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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

 

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

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