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I wrote this book several years again and am in the process of creating a new, more complete text on the subject. Please feel free to download and share. All I ask is that you leave some comments on what you liked or disliked about it.

If you need any assistance with resolving energy, sleep, digestion, mood, libido, pain or other hormone issues then please check out the members area for more information or even the free resources section.

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A Bioenergetic Approach to Restoring Gut Function: Part 2

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Oops - A bioenergetic approach to restoring gut function part 1 was almost two years ago, my studies got the better of me, I’m sorry. Following on from the information of how to restore energy and digestion by simply removing foods that are difficult to digest, promote endotoxin, decrease energy and digestion. Replacing them with easily digested, protective nutrients can negate the need for expensive, reduced testing and a supplement list that causes you to rattle as you stroll down the street. Much like the decreased need for stool testing, I have rarely recommended a food allergy or sensitivity test for the same reason that I haven’t used a stool test for many years (or had the luxury of a nice cash kickback from the labs I used to use). Why? Because these tests show the body in a stressed, energy wasting state that is prone to inflammation and reacts with many foods like dairy. Is it the food? No. Could it be you? It’s possible.

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It’s not the dairy it’s you

Elie Metchnikoff suggested over 100 years ago that as putrefaction within the bowel occurs, function and immunity is compromised

 

Many clients have rolled into the office clutching their food sensitivity tests in a file, with dozens of other tests. Red bars, yellow bars, all highlighting so called problem foods. During bouts of stress (pollution exposure, psychological, under eating etc, excessive exercise, poor sleep) the body is prone to decreasing available levels of organisational hormones such as thyroid and progesterone. Usually the adrenal glands have to pick up the slack and compensatory stress hormones such as cortisol, glucagon, adrenaline and activation of serotonin (not a hormone) which  suppress thyroid and progesterone are perpetuated. This often creates a high sodium (salt) and magnesium wasting state and poor digestive function that facilitates increased sensitivity via increased serotonin and histamine levels. This also increases demand for vitamin C for gut mucosa maintenance and adrenal responses.

If this state is perpetuated increases in endotoxin (the by-product of bacterial metabolism and degradation ) burden the digestive system, liver, and can damage the gastrointestinal lining. Endotoxin levels are also  increasing through airborne environmental pollutants such as polycyclic aromatic hydrocarbons  from fossil fuel use and industry (Annamalai & Namasivayam, 2015), so it’s worth considering that some people in a high pollution area, with poor digestive function are at increased risk of presenting with food sensitivities. They get tested, part with their cash and told to cut out 20 foods that they eat on a regular basis. Problem solved? Well no, it’s an intervention that will have some success but it’s some distance of what the person really needs.

 To simplify some of the well-known digestive issues with two ends of the spectrum.

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Restore function

Restore appropriate movement

Constipation – failure to go to poop daily, hard to pass.

 

IBS irritable bowel like issues. Loose often more than 3 times per day.

 

There’s plenty of reasons to link constipation with a low energy, functionally hypothyroid, subclinical or overt hypothyroid state (Lauritano et al., 2007) and increased bacterial overgrowth like SIBO or small intestinal bacterial overgrowth. The digestive system is energy and thyroid hormone dependant and restoring energy by supplying easily digested high energy foods can be a simple intervention with effective results.

Often when you dig into a person’s history, you might find that those with IBS like states often describe a period of constipation. It’s not impossible to suggest that sustained constipation will lead to increased endotoxin, serotonin and histamine that damages the bowel lining. When this environment is perpetuated by stress, poorly digested foods and low energy, the digestive system is maintained in a high stress state, sensitive and ready to reject any remotely objectionable substance. Any food can become problematic when the digestive system is over-burdened or sustains damage to enzyme producing structures in the villi and microvilli.

 If you follow the chart suggested in restoring gut function part 1, you should find yourself in a much improved state. If you need further improvement then the following factors have always worked well:

 

Constipation:

 Magnesium in forms such as chloride and glycinate or very useful for decreasing perceived stress and lowering the incidence of sensitivities and 400mgs to 1g is useful to experiment with and complements dietary changes suggested.

To restore bowel movement magnesium sulphate or Epsom salts will mobilise the digestive tract and I have found that clients if needed try half to a full teaspoon to grease the wheels.

Vitamin C is a great way of decreasing constipation. A few years back I would recommend a dose of 1-2 grams  but equally I feel adequate intake of orange juice will do a great job. The added benefit of orange juice (polyphenols) has been shown to decrease inflammation and endotoxin which is often present in both high fat and carbohydrate meals (Ghanim et al., 2010).

 

Cascara Sagrada If you need a good clear out to restart function then cascara is an extremely effective solution.


‘ An effective laxative (besides preventing inflammation) causes not only coordinated contraction of the smooth muscles of the intestine, but also adjusts secretions and absorption, so that an appropriate amount of fluid stays in the intestine, and the cells of the intestine don’t become water-logged.’ Ray Peat.

 

Caffeine seems a logical choice and the research on caffeine as a potent factor in the fight against cancer and neuro degenerative diseases such as dementia and Alzheimer’s disease is very positive. Coffee stimulates bowel function and like the suggestions above is useful to decrease the reabsorbed metabolites and toxins that may be instrumental in systemic inflammation. The aerobic/respiratory system is enhance and protected by coffee consumption, providing protection to the mitochondria (Eskelinen & Kivipelto, 2010).

 

Irritable bowel

Carrots I have posted about the power of grated carrot to reduce the irritated state many times and have seen some clients with over 20 years of IBS resolve with this simple addition. Carrots act as a natural antibiotic, lowering endotoxin and other bacterial end products (Babic, Nguyen‐the, Amiot, & Aubert, 1994) and bamboo shoots have the same effect. As increased bacterial issues stimulate endotoxin production the daily use of a carrot salad can be one of the simplest yet most effective tools that you can have to improve bowel function.

Bone broth, gelatin and glycine are also great for helping to support gastrointestinal mucosa, improve the brush border enzyme function and decrease the proinflammatory effects of eating tryptophan and iron rich muscle meats that can also irritate the bowel when excessive.

Mushrooms  when boiled also have a similar effect as the carrot by decreasing aromatase enzymes and estrogen  acting as a natural antibiotic.

I would challenge anyone who either has paid money for a food sensitivity test or who is thinking about it ,to simply try the suggestions set out in these two posts. Over the last few years I haven’t seen anyone who has failed to improve digestive function. Although sometimes other mechanisms involving hormones may need to be explored.

References:

Annamalai, J., & Namasivayam, V. (2015). Endocrine disrupting chemicals in the atmosphere: Their effects on humans and wildlife. Environment International. http://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. http://doi.org/10.1111/j.1365-2672.1994.tb01608.x

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). http://doi.org/10.3233/JAD-2010-1404

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. http://doi.org/10.3945/ajcn.2009.28584

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

 Peat, R. http://raypeat.com/articles/articles/cascara-energy-cancer-fda-laxative-abuse.shtml

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.

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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

 

Better gut health with less bacteria?

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

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

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

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

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

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

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

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

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

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

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

References:

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

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

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

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

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