methylene blue

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.

Hyperphosphorylated tau.jpg

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.

 

How to keep your energy chain maintained. Protective compounds.

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

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

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

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

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

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

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


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

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

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

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

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

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

Cell enhancers

Cell enhancers

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

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

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

References:

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

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

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

  4. Masterjohn, C. Thyroid Toxins Report. 2007

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

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

http://www.keithlittlewoodcoaching.com

Sunlight, health and cancer

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

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

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

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

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

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

Promoting better conversations between structures     

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

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

Estrogen

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

Thyroid failure

Hypothyroidism is well known to create disorganised tissue and its effects extend to all areas of physiology which include metabolism, fertility, mood, cognition and is instrumental in heart disease. As the need for thyroid hormone increases or the gland fails TSH or thyroid stimulating hormone - the pituitary hormone used to stimulate thyroid hormone increases, or at least it should do as a normal response. TSH has been associated with many pathological states but has been increasingly linked with melanoma (Ellerhorst et al., 2006). It appears that nearly all TSH receptors (TSHR) are present within melanoma cells and play a role in proliferation. Whilst the pituitary response and TSH is known to rise to increase thyroid hormone in response to increased need or thyroid failure. This action is a back-up and comes at a cost of increasing pituitary stimulation. Another factor for protection of the skin is that thyroid blood tests may not be accurate when individual nutrition, environmental pollutants and other stressors are present. Increased TSH is one factor, low undetectable thyroid function, poorly defined by blood tests could be another factor in skin damage that may not be picked up by clinicians.

Fat status of tissues.

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

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

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

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

References:

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

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

Ellerhorst, J. A., Sendi-Naderi, A., Johnson, M. K., Cooke, C. P., Dang, S. M., & Diwan, A. H. (2006). Human melanoma cells express functional receptors for thyroid-stimulating hormone. Endocrine-Related Cancer. https://doi.org/10.1677/erc.1.01239

Mungenast, F., & Thalhammer, T. (2014). Estrogen biosynthesis and action in ovarian cancer. Frontiers in Endocrinology, 5(NOV). http://doi.org/10.3389/fendo.2014.00192

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

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

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

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

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

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

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

Methylene Blue - Let’s play the blues.

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

MB.jpg

Restoring respiration with colour.

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

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

  • Tissue hypoxia

  • Hyper dynamic circulation of the liver post cirrhosis

  • Improved low blood pressure states

  • Hepato-pulmonary syndrome

  • Anti malarial agent

  • Improves mitochondrial function

  • Detects parasites such as h-Pylori

  • With additional treatment of red light has anti-parasitic effects.

  • Anti-microbial-kills MRSA

  • Hepatitis C and other conditions also effectively treated in tandem with red light application.

  • Anti-Alzheimer’s agent- attenuates amyloid plaques (which are often protective and responsive to bacterial/endotoxin/pollutant damage so presumably threat is decreased) and improves mitochondrial function.

  • Improves Parkinson disease states

  • Improves thyroid hormone availability

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

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

Metabolic enhancer:

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

I managed to find several papers on the restorative and protective effects of MB to improve T3 levels within the blood and lower TSH. MB also seems to arrest estrogen stimulated pituitary growth and tumour development (Schreiber, Nedvídková, & Jahodová, 1993) (Haluzik, Nedvidkova, & Schreiber, 1995) (Nedvídková, Pacák, Haluzík, & Nedvídek, 2000).

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

Anti parasitic

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

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

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

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

I quote Ray Peat with the following:

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

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

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

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

A neurological restorer?

There are plenty of studies (in rodents) supporting the restorative effects of MB to the central nervous system. Improvements to cognition, smell, movement and other factors related to senescence and neuro degeneration seem to be improved or at least slowed (Smith et al., 2017) (Atamna et al., 2008) (Biju et al., 2018). Often when pollutants and endotoxin are able to cross the blood brain barrier an increase in protective beta amyloids (AB) can be observed often as an antimicrobial response and to prevent damage but also affects the tau structures in the brain. Damaged/entangled tau appear to be improved and decrease necessary AB with use of MB. The resistance of pro-metabolic therapies in areas of disease such as dementia, Parkinson’s and even cancer should be questioned when compounds like MB seem to have such restorative effects to the oxidative system, neurological function and beyond.

What I have learnt from taking MB.

I found that if I took doses of more than 5mg total within a day or two of each other, my urine turned blue. A self -limiting factor that probably suggests that I was taking too much. I also had the odd crazy dream. I generally found that a total intake of 2.5 mgs or around 5 drops 2-3 days per week seemed to serve me well. I titrated up and found the optimal dose, something which I strongly recommend doing for all but much higher doses have been found to medically safe (whatever that means these days). It should also be noted that medical IV dosing, which probably has more beneficial effects on blood borne parasites will differ from oral administration.

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

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

References:

Atamna, H., Nguyen, A., Schultz, C., Boyle, K., Newberry, J., Kato, H., & Ames, B. N. (2008). Methylene blue delays cellular senescence and enhances key mitochondrial biochemical pathways. FASEB Journal. https://doi.org/10.1096/fj.07-9610com

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

Biju, K. C., Evans, R. C., Shrestha, K., Carlisle, D. C. B., Gelfond, J., & Clark, R. A. (2018). Methylene Blue Ameliorates Olfactory Dysfunction and Motor Deficits in a Chronic MPTP/Probenecid Mouse Model of Parkinson’s Disease. Neuroscience. https://doi.org/10.1016/j.neuroscience.2018.04.008

Ginimuge, P. R., & Jyothi, S. D. (2010). Methylene blue: revisited. Journal of Anaesthesiology, Clinical Pharmacology, 26(4), 517–20.

Haluzik, M., Nedvidkova, J., & Schreiber, V. (1995). Methylene blue--an endocrine modulator. Sb Lek.

Meissner, P. E., Mandi, G., Coulibaly, B., Witte, S., Tapsoba, T., Mansmann, U., … Müller, O. (2006). Methylene blue for malaria in Africa: Results from a dose-finding study in combination with chloroquine. Malaria Journal, 5. http://doi.org/10.1186/1475-2875-5-84

Oz, M., Lorke, D. E., & Petroianu, G. A. (2009). Methylene blue and Alzheimer’s disease. Biochemical Pharmacology, 78(8), 927–932. http://doi.org/10.1016/j.bcp.2009.04.034

Nedvídková, J., Pacák, K., Haluzík, M., & Nedvídek, J. (2000). The regulation of adenohypophyseal prolactin secretion: Effect of triiodothyronine and methylene blue on estrogenized rat adenohypophysis. Physiological Research.

Schreiber, V., Nedvídková, J., & Jahodová, J. (1993). Anterior pituitary weight, cAMP, cGMP and prolactin levels after combined treatment with estradiol and methylene blue. Physiological Research / Academia Scientiarum Bohemoslovaca.

Smith, E. S., Clark, M. E., Hardy, G. A., Kraan, D. J., Biondo, E., Gonzalez-Lima, F., … Lee, H. J. (2017). Daily consumption of methylene blue reduces attentional deficits and dopamine reduction in a 6-OHDA model of Parkinson’s disease. Neuroscience. https://doi.org/10.1016/j.neuroscience.2017.07.001

Ray Peat quote originally taken from a YouTube interview with Andrew Murray. (cant recall which one)

https://www.google.com/patents/WO2007038201A1?cl=en 6. http://valtsus.blogspot.ae/ contains over 2500 LLLT studies and is by far the best resource available on the actions of LLLT.