metabolism

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/

 

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

 

 

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

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.

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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.





Adrenal fatigue or reductionist thinking? Part 2: Restoration of metabolic processes

adrenal Restoration of metabolic process- lowering the adrenal load.

Sugar, fat and other mal-aligned  factors.

Saturated fat is bad for you, so they said but it clearly wasn’t. Now it’s sugars turn. Sugar causes diabetes, cancer and many other modern conditions, if you are to believe many of the memes on social media. Well no, it doesn’t. Cancer for example is usually created from a specific defect to the respiratory apparatus of the cell. In English that means part of the cell that utilises oxygen. Sugar or Sucrose whose primary constituents are both Fructose and Glucose are readily available carbohydrates and the brain/central nervous system require plenty. Have you ever noticed that brain fog creep in when on that low carb diet? The reason? Restricted carbohydrates  equals reduced cognitive process’s. Yes we can generate glucose via oxidation of fat, in the form of ketosis and you can also break down protein to generate glucose too, but these methods are less than efficient forms of energy generation and long-term utilisation of these systems is not ideal.

Sugar produces energy and when processed with oxygen is much more efficient than glycolysis or energy production without oxygen (anaerobic). In those who have damaged metabolism, there is a reliance on the production of energy in this manner, lactic acid is often produced even at rest. Therefore trying to exercise at intense levels poses a problem for those with both adrenal and metabolic issues.

Give the body what it needs?  Got cravings? You know those ones where you are dying for some food, starchy carbohydrates, a sugary drink? There are no demons at work here, just a simple case of biology, carbohydrates are a primary fuel source for the body. Want to avoid coming crashing down? Avoid having 3 big meals a day and maintain blood sugar levels by eating frequently. Some do better than others but allowing 4-6 meals a day and noting how you feel is a step in the right direction. Maintaining a body temperature of 37 degrees and a pulse rate of 70-85 beats per minute is ideal. This has been well documented in the work of thyroid researcher Broda Barnes and the work of Ray Peat PhD.

Eating readily available carbohydrates such as ripe digestible fruits, protein and saturated fats (in the right amounts) such as coconut oil help to maintain blood sugar levels throughout the day without the resultant elevations in cortisol, which affect adrenal regulation issues.

Stressful situations often warrant the use of supplements such as Vitamins A, B6, C, magnesium and potassium. In particular sugary foods, which should include fruit, maple syrup and honey are ideal choices to diminish the stress response (even table sugar could play a therapeutic role in lowering stress).

Salt is also a powerful anti-stress compound. During stress sodium is often passed more rapidly from the body. Sodium spares magnesium. If you drink too much water the level of sodium excretion increases, which further decreases available magnesium. The research on lowering salt intake is inconclusive but what is known, is that when a low sodium state exists, aldosterone, a hormone that is used to regulate both salt and blood pressure elevates in response. It would come as no surprise that in a low adrenal state, feeling dizzy when moving from seated to standing exits due to poor blood pressure regulation. Craving salt is a mechanism to improve such a situation.

The current mind set regarding exercise and wellbeing is

Increased exercise + Low carb and raw foods = Health

And in the short term, markers suggest that this could be favourable. So how do you tell if this working for you long term? The monitoring of both pulse and body temperature give a great insight into optimal biological function. Here are some of the symptoms, which combine both compromised cortisol and thyroid function.

  • Cold hands, feet and nose
  • Energy crashes
  • Poor wound healing
  • Poor sleep
  • Fatigue
  • Constipation or alternation between constipation and diarrheoa
  • Weight gain
  • Bloating
  • Skin issues
  • Low libido

In reality:

Intense exercise + low carb/raw food diets= compromised metabolism.

Historically in many, changing both the way you eat and completing more exercise may have worked previously, but as you push the markers of exercising more and eating less or certainly eating foods that do not support your activities. You may see many of those symptoms above start to creep into your daily life. There’s no doubt that eating well and exercising are productive pursuits for optimal body function. However for many the lines are blurred as to what actually is a healthy diet.  Consumption of large amounts of grains, margarine and low fat foods were being touted as healthy a decade or two earlier, now look at the research condemning that approach. The following information seems to be heading a similar route.

For the health conscious exerciser today a diet high in raw green vegetables, green juices, seeds nuts, fish oils, low carb, low starch seems to be the zeitgeist but is it that healthy? From a biological perspective the answer would be no. Eating these foods over a long period of time not only increases the stress response but may actually damage how our body’s cells actually function. Increasing available energy from easily digestible foods helps to assimilate energy for production. In contrast foods such as many raw green vegetables, nuts, seeds and vegetable oils, not only irritate the bowel, sit and accumulate bacteria damaging the intestinal lining, but also provide less than optimal nutrition, which will lower metabolic rate.

Moving is important, no doubt, but exercising to within an inch of total fatigue can be detrimental, especially so when dealing with issues related to both adrenal and metabolic based issues. Finding the right type of exercise and even stepping back and focusing on exercise that doesn’t produce high levels of lactic acid, causes hyperventilation and the loss of carbon dioxide should be considered in the short term. The goal of improving metabolic function, restoring deep sleep and raising energy should always predominate over the loss of body fat reduction. It’s a tricky issue to get your head around for some, but when you start to feel great again. You’ll understand why.