dementia

Improving brain health - amyloid, tau, and energy

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

The Verve - The Drugs Don't Work

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

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

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

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

Dietary fats, glucose and thyroid.

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

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

Endotoxin, gut and blood brain barrier.

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

 

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

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


References:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

 

A Bioenergetic Approach to Restoring Gut Function: Part 2

Copy of Your bowel function might be an expression of your biology.jpg

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.

Metchnikoff.png

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.

Your bowel function might be an expression of your biology.jpg

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