SSRIs, fungi, and exotic botanicals

This post is about comparing my experiences with fluoxetine (Prozac – an SSRI), psilocybe mushrooms, lion’s mane mushroom, and yerba mate tea. Of course this is my personal experience, not a medical study. Remember that everyone is affected differently by psychoactive compounds. In fact recently my friend told me an interesting scientific theory in regards to why humans differ a lot psychologically. Have you heard of fungi that make ants climb on top of a leaf, hook themselves, and stay there without eating, basically committing ant suicide? The spores of the fungi then burst from the ant and go on to grow into new fungi. Ophiocordyceps unilateralis is called the zombie-ant fungus.

“Researchers think the fungus, found in tropical forests, infects a foraging ant through spores that attach and penetrate the exoskeleton and slowly takes over its behavior.

As the infection advances, the enthralled ant is compelled to leave its nest for a more humid microclimate that’s favorable to the fungus’s growth. The ant is compelled to descend to a vantage point about 10 inches off the ground, sink its jaws into a leaf vein on the north side of a plant, and wait for death.

Meanwhile, the fungus feeds on its victim’s innards until it’s ready for the final stage. Several days after the ant has died, the fungus sends a fruiting body out through the base of the ant’s head, turning its shriveled corpse into a launchpad from which it can jettison its spores and infect new ants.”

So what does this have to do with humans being different? The theory says that humans evolved to react differently to same psychoactive molecules in order to not become victims to simple fungi organisms. Since the infectious fungi are not very complex organisms, they can only release so many molecules. By evolving to have complex brains and having individuals react differently to the same psychoactive molecule, humans became resistant to being overtaken by simple fungi. The theory is that there is no one molecule that a fungi could produce that would make all humans act the same, stop whatever they were doing, walk to a nice moist and wooded area, lie down, and wait for fungi spores to emerge from them.

Back to fluoxetine and shrooms

Fluoxetine

Fluoxetine is a selective serotonin reuptake inhibitor. N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine.  It delays the reuptake of serotonin, resulting in serotonin persisting longer when it is released. Also dopamine and norepinephrine may contribute to the antidepressant action of fluoxetine in humans.

From wiki: Fluoxetine elicits antidepressant effect by inhibiting serotonin re-uptake in the synapse by binding to the re-uptake pump on the neuronal membrane to increase its availability and enhance neurotransmission. Norfluoxetine and desmethylfluoxetine are metabolites of fluoxetine and also act as serotonin re-uptake inhibitors, so increase the duration of action of the drug. Fluoxetine appeared on the Belgian market in 1986. In the U.S., the FDA gave its final approval in December 1987, and a month later Eli Lilly began marketing Prozac.

fluoxetine

Fluoxetine is one of medications considered to be effective for PMDD (premenstrual dysphoric disorder). Also research indicates that low doses of fluoxetine could help with PMS. PMS appears to be triggered by the fall in secretion of the ovarian sex steroid hormone progesterone that occurs towards the end of the menstrual cycle and leads to a decline in its breakdown product allopregnanolone, which acts in the brain as a potent sedative and tranquilising agent. In other words, women with PMS are undergoing a type of drug withdrawal response from an in-built, tranquilising steroid chemical in their brains. New research shows that antidepressants such as fluoxetine inhibit a specific enzyme in the brain, which deactivates allopregnanolone, therefore maintaining the chemical balance of this in-built tranquiliser in the brain. Recent findings published in the British Journal of Pharmacology, show that short-term treatment with a low dose of fluoxetine immediately prior to the rat’s premenstrual period not only raised brain allopregnanolone and prevented the development of PMS-like symptoms but also blocked the increase in excitability of brain circuits involved in mediating the stress and fear responses that normally occur during this phase of the cycle.

Enzyme identified that could lead to targeted treatment for PMS

A review of studies found that fluoxetine was more tolerabled by female patients than tricyclic amine antidepressants (Amitriptyline, Imipramine). ” In this study, a retrospective analysis of 11 randomized, double-blind, well-controlled trials was done to compare data from 427 female patients on fluoxetine and 423 female patients on TCAs. Both fluoxetine and TCAs significantly reduced the HAMD17 total mean score from baseline to end point, week 5 (fluoxetine, 24.35 to 14.37; TCAs, 24.57 to 14.43; p < 0.001). Both treatment groups were associated with significant reductions in the HAMD17 anxiety/somatization and insomnia subfactor scores. Abnormal vision, constipation, dizziness, dry mouth, and somnolence occurred more frequently (p < 0.05) in the TCA group. Insomnia and nausea were the only adverse events more common (p < 0.05) in the fluoxetine group. This study demonstrates that fluoxetine is an effective and tolerable agent for the treatment of major depressive disorder in women.”

Fluoxetine vs. tricyclic antidepressants in women with major depressive disorder

My experience with fluoxetine – the first time that I took 10mg of fluoxetine, I felt a difference in less than three hours. It was as if I was taken out of a dark basement and into a sunny day in July. Unfortunately I also experienced insomnia that did not go away and I had a sense of apathy, in the end I stopped taking fluoxetine, but I know many women who swear by it.

Psilocybin

Next I will mention psilocybin. Psilocybin is a psychedelic compound produced by more than 200 species of mushrooms. Psilocybin is quickly converted in human body to psilocin. Psilocin is a prtial agonist for several serotonin receptors. An agonist is a chemical that binds to a receptor and activates the receptor to produce a biological response. Recently there has been increased reseach interest in psilocybin and how it could help with depression.

“A landmark study conducted by the Beckley/Imperial Research Programme has provided the first clinical evidence for the efficacy of psilocybin-assisted psychotherapy to treat depression, even in cases where all other treatments have failed. We gave oral psilocybin to 20 patients with treatment-resistant depression, all of whom had previously tried at least two other treatment methods without success. Participants had suffered from depression for an average of 18 years, with severity ranging from moderate to severe. Each patient received two doses of psilocybin (10 and 25mg) 7 days apart, accompanied by psychological support before, during, and after each session. All participants also underwent brain scans to investigate the neural underpinnings of psilocybin mechanisms of action on depression. Follow-up examinations were carried out at 5 weeks, and three and six months. Results highlights All patients showed some reductions in their depression scores at 1-week post-treatment and maximal effects were seen at 5 weeks, with results remaining positive at 3 and 6 months. Notably, reductions in depressive symptoms at 5 weeks were predicted by the quality of the acute psychedelic experience. The drug was also well tolerated by all participants, and no patients sought conventional antidepressant treatment within 5 weeks of the psilocybin intervention. While it is important to note that this was a relatively small study with no control group, placebo, or ‘blinding’ (meaning participants were fully aware what they were getting), the results are extremely encouraging and confirm that psilocybin is safe to give to depressed patients, warranting further research into this area.”

Sceletium tortuosum (Kanna) – a plant commonly found in South Africa.  Laboratory studies have found that Sceletium alkaloids are selective serotonin reuptake inhibitors (SSRIs). Thus, they have the same action as pharmaceutical SSRIs such as Prozac. Animal studies have found that Sceletium can improve mood and reduce anxiety-related behaviours.

 

 

Restarting probiotic foods

So I am restarting probiotic foods. I suppose I had a bad start when I went all in and started consuming everything at once – yougurt, kefir, sourdough, yeast supplements, probiotic capsules. I was also fermenting apples, vegetables, plantains, trying to make my own chickpea tempeh. Home fermentation could go wrong at some point, also I think the supplements were a bad choice. Maybe taking saccharomyces boulardii for a week could improve gut microbiome, but taking the capsules everyday for several months I think for me led to SIBO (small intestinal bacterial overgrowth, in this case there was also yeast).

I think at first when I started eating goat yougurt and drinking homemade kefir, I felt better. I remember there were several days when I was helping put up posters for a missing person – the man was my close friend’s co-worker. He was last seen at a bar on a Friday night but never made it home. I didn’t personally know the guy, but since I was putting up the posters and was part of a Facebook search group, I’ve learned a lot of details about his girl friend, his parents. A week later his body was found in lake Ontario and it really got to me. I know that this tragic ending of a search for a missing person would be painful for anyone in the search group, but with depression I think such event further triggers a cascade of negative thoughts about your own life. I didn’t know the guy, I didn’t know his parents, nor his girl-friend. It was their loss, this was not about me, but anxiety and depression always find a way to relate events to your own personal issues. I remember feeling overwhelmed with anxiety and physical pain, as if it was me who let something bad happened and now I would be punished for it. I couldn’t let go of the fear of punishment for things that were happening in the world. There was a sense that I had to fix them. Maybe when I was younger I would imagine that I have these feelings because I am a morally better person, but now I know that no, feelings of guilt and fear of punishment is depression showing through.

That weekend coincidentally was also when my first batch of goat kefir was ready. The day when I tried the first cup of kefir, I had continued sense of guilt and fear. I felt guilty for trying to feel well when such tragic things were going on in the world. I have already been through a lot of cognitive behavioural therapy by that point, so logically I understood that I was not obliged to feel unwell or be responsible for the world,  but the feeling was still there. This was more than a year ago, but I do remember feeling more calm the next day after starting goat kefir and letting go of some of the guilt. It wasn’t a complete relief, but I remember  no longer feeling overwhelmed and on the verge of tears.

Studies on probiotics and mental health are inconclusive. “A recent article in Annals of General Psychiatry reviewed the currently available medical literature on using probiotics to treat anxiety and depression. The doctors identified 10 studies that were well done (in other words blinded and placebo-controlled), and looked at each study in depth. All of these studies had relatively small numbers of patients, ranging as from as few as 42 to as many as 124. The results of these studies were mixed; some suggested that there may be mild benefits of taking probiotics if you have anxiety or depression while other studies showed no benefit. Overall, the authors concluded “the clinical effects of probiotics on mental health have yet to be studied comprehensively.” 

Can probiotics help treat depression and anxiety?

Probably just adding kefir to your diet will not cure mental issues, but I do enjoy drinking it, the sour yet creamy taste. It is also a source of calcium and protein. A glass of kefir has less sugar than a glass of milk since the bacteria and yeast from kefir grains break down the milk sugar lactose and convert it into lactic acid. “The only sugar naturally present is milk is lactose (is a sugar composed of galactose and glucose subunits). Most microorganisms lack the enzyme lactase which is required to break lactose into its two component sugars, namely, glucose and galactose. Lactic acid bacteria which do have lactase readily break down lactose and use glucose as an energy source. Lactic acid bacteria, therefore, have a competitive advantage in milk; that is, they are able to out grow other bacteria which are unable to obtain glucose from lactose. Further, some lactic acid bacteria are able to convert galactose to glucose.” Therefore when we drink kefir, the bacteria had already used up glucose and galactose for energy and therefore we don’t get glucose from the drink. When humans drink milk, it contains the sugar lactose. We have a protein named lactase that is produced in our small intestine. Lactose is then broken down by lactase into galactose and glucose, which is then absorbed into bloodstream. Therefore drinking non-fermented milk raises blood sugar more than kefir.

Is it safe to make kefir at home?

The good news is that fermentation of warm milk by lactic acid bacteria reduces milk pH to less than 4.0 and in turn makes the environment unlivable for pathogenic bacteria. Most organisms grow best at pH near physiological pH of 6.8, and not in acidic environments. I assume it would be great though for microbes from Yellowstone National Park acidic pools. these pools are usually of temperature ranging from 65 to 90 degrees Celsius and contain high sulfur contents, either as hydrogen sulfide (H2S(g)) emitted as a volcanic gas, or as elemental sulfur crystals. Who lives there – thermoacidophiles, a unique group of bacteria that are a combination of acidophiles and thermophiles. Thermoacidophiles are characterized by their exclusive ability to live in both highly acidic environments and also high temperatures. The typical conditions these thermoacidophiles live under include pH at around 2 with temperatures ranging from 80 to 90 degrees Celsius.

I am not sure if thermoacidophiles  are likely to contaminate homemade kefir, but I do sterilize my jars by pouring boiling water over them. Then I let the jar cool, place the kefir grains in, pour in milk, and cover with a coffee filter. I ferment my kefir at room temperature for 24 hours. Kefir is a versatile food as it can be drank on its own, used for smoothies, used to make tvorog (quark), syrniki (fried quark pancakes), and oladyi (fritters). Easy breakfast recipe – in the evening combine kefir, sorghum flour, ground oatmeal, egg, salt, and avocado oil in a bowl and let it stand overnight in the fridge. In the morning preheat a frying pan and then use the dough for fritters. Consume with honey and yougurt on top.

Who inhabits kefir?

The kefir grains initiating the fermentation consist of a symbiotic culture of lactic acid bacteria and yeasts embedded in a matrix of proteins, lipids, and polysaccharides. The matrix is formed by microbial activity, with color ranging from white to creamy yellow. Grains can include lactic acid bacteria, acetic acid bacteria, and yeasts. During fermentation, changes in the composition of ingredients occur. Lactose, the sugar present in milk, is broken down mostly to lactic acid (25%) by the lactic acid bacteria, which results in acidification of the product. Propionibacteria further break down some of the lactic acid into propionic acid. Other substances that contribute to the flavor of kefir are pyruvic acid, acetic acid, diacetyl and acetoin (both of which contribute a “buttery” flavor), citric acid, acetaldehyde, and amino acids resulting from protein breakdown. The slow-acting yeasts, late in the fermentation process, break lactose down into ethanol and carbon dioxide. Usually ethanol concentrations are 0.2–0.3%, so kefir is not much of an alcoholic beverage.

Probiotic bacteria found in kefir products include: Lactobacillus acidophilus, Bifidobacterium bifidum, Streptococcus thermophilus, Lactobacillus delbrueckii subsp. bulgaricus, Lactobacillus helveticus, Lactobacillus kefiranofaciens, Lactococcus lactis, and Leuconostoc species. Lactobacilli in kefir may exist in concentrations varying from approximately 1 million to 1 billion colony-forming units per milliliter, and are the bacteria responsible for the synthesis of the polysaccharide kefiran. In addition to bacteria, kefir often contains strains of yeast that can metabolize lactose, such as Kluyveromyces marxianus, Kluyveromyces lactis, and Saccharomyces fragilis, as well as strains of yeast that do not metabolize lactose, including Saccharomyces cerevisiae, Torulaspora delbrueckii, and Kazachstania unispora.

Kefir is made by adding kefir grains to milk typically at a proportion of 2-5% grains-to-milk. The mixture is then placed in a corrosion-resistant container, such as a glass jar, and stored preferably in the dark to prevent degradation of light-sensitive vitamins.

Hymenolepis diminuta observations and paper

As described in my previous posts, I have started HDC helminth therapy on June 4th. It has now been over a month. So far I have taken HDC three times – 10 on June 4th, 10 on June 9th, and 20 on June 25th. I have also updated my NA by adding three more on July 6th. It has now been over two weeks since my last HDC dose, helminth therapy wiki suggests dosing every two weeks and adult dosing is in range 30-60 HDC bi-weekly. I am waiting for my next order of 20, the delivery has been slow, and it’s expected to arrive on Friday. After that I plan to increase the dose to 30 as is advised, 20 may be not enough of a therapeutic dose for an adult.

One important observation is that during my period, which happened soon after the third dose of HDC, I did not have to take any pain relievers. I see this as not just a coincidence because last such occurrence happened almost a year ago in July 2018, after I started NA therapy. After that one time unfortunately pain levels during periods went back to usual unbearable and as usual I would take at least two Naproxen gels, sometimes also an ibuprofen. Several times I had to leave work early or work from home. Therefore I was quite surprised that when my period occurred in the end of June the pain began as usual but did not increase to unbearable levels. I went to work as usual, I always keep Naproxen in the drawer in the office and at home, but the pain never rose to the level where I would need a pain killer. I would say that just for this benefit HDC is already worth continuing as not being crippled by pain made me feel more free. Even though it’s not my fault, I often feel guilty leaving home early or asking to work from home every month. I am also not pleased with having to take Naproxen as for me it causes acid reflux and it makes me think that I am undoing the benefits of my efforts to heal the gut.

Another observation was recently increased heat tolerance.  In beginning of July temperatures rose to over 30 degrees Celsius and there is no central AC where I live. In order to cool down the house, I usually have to install two window air conditioner units. These units were taken down for the winter, so there were several days of temperatures around 30 degrees inside. I noticed that my sleep was not as disrupted as it previously would during heat. Also in general I was not as incapacitated by the temperature, I did feel lethargic, but did not have as severe indecisiveness nor mood swings exacerbation that often occur for me during summer heat.

The new lab test results are also encouraging. Free T4 and T3 stayed at the same levels, within normal range. TSH went down to 2.0, which is below the previous value of 2.58. This is a positive result, since some research indicates that the optimal cut- off value of TSH is 2.5 MIU/L. Anti-TPO antibodies have also decreased.

TSH cut off point based on depression in hypothyroid patients

test_jul2019

On a side note, I found that someone wrote their undergrad honors thesis on Hymenolepis diminuta. “Impacts of Hymenolepis diminuta (benign helminth worm) colonization on chronic pain and the central nervous system in Sprague Dawley rats“. If I would go back in time, I would prefer to also study neuropsychology. Unfortunately in my undergrad I was calculating bond and option prices. Glad to hear whenever someone is doing research on treatments for autoimmune disorders, specifically the connection between neuropsychiatric problems and inflammation. “The results from this project partially support the tenets of the hygiene hypothesis. Though behavioral results following CCI surgeries were inconclusive, molecular investigation of cytokine levels in the hippocampus showed promotion of an anti-inflammatory cytokine milieu due to the upregulation of IL-10 and downregulation of its receptor. These promising results guide future research toward investigation of cytokine levels in other brain regions, such as the amygdala.

Impacts of Hymenolepis diminuta (benign helminth worm) colonization on chronic pain and the central nervous system in Sprague Dawley rats

HDC Therapy for autoimmune disorders

HDC, hymenolepis diminuta cysticercoids, is a larvae stage of a nice and friendly rat tapeworm, an adult of this species can be 20-60cm long. You might have a thought now “what am I reading and why?”, but hold on. Humans are not the usual host of hymenolepis diminuta, rats are, and in humans this helminth does not develop into an adult. There have been very few cases documented of humans being infected with adult HD. For this reason the HD larvae, HDC, is one of the species chosen for helminthic therapy as it does not reproduce inside humans, stays in the gut, does not reach adult size, and yet modulates the immune system as it tries to survive.

HDC survive in humans only for about two weeks, therefore for continuous therapy, HDC would need to be ingested at these intervals. HDC will live in the small intestine and attach to the intestine wall. There are no reports in the scientific literature of H. diminuta mis-migrating to other organs in humans. In a scientific review of helminthic therapy from 2016, HDC was listed as one of the more popular helminths:

Five physicians monitoring more than 700 self-treating patients were interviewed. The results strongly support previous indications that helminth therapy can effectively treat a wide range of allergies, autoimmune conditions and neuropsychiatric disorders, such as major depression and anxiety disorders. Approximately 57% of the self-treating patients observed by physicians in the study had autism. Physicians reported that the majority of patients with autism and inflammation-associated co-morbidities responded favourably to therapy with either of the two most popular organisms currently used by self-treaters, Hymenolepis diminuta and Trichuris suis. However, approximately 1% of paediatric patients experienced severe gastrointestinal pains with the use of H. diminuta, although the symptoms were resolved with an anti-helminthic drug. Further, exposure to helminths apparently did not affect the impaired comprehension of social situations that is the hallmark of autism. These observations point toward potential starting points for clinical trials, and provide further support for the importance of such trials and for concerted efforts aimed at probing the potential of helminths, and perhaps other biologicals, for therapeutic use.

Practices and outcomes of self-treatment with helminths based on physicians’ observations

Here is another paper from 2017 reviewing HDC use by self-treating individuals. Unfortunately there are not many clinical trials with treatment and control groups, therefore we have to rely on information on experiences from people like me who are obtaining helminths and treating themselves. ” In this study, we describe the production and use of HDCs in a manner that is based on reports from individuals self-treating with helminths, individuals producing helminths for self-treatment, and physicians monitoring patients that are self-treating.” The authors from Duke University are quite optimistic about helminthic therapy: “Helminthic therapy, the use of helminths to treat disease, offers the best hope of decreasing inflammation via immunomodulation rather than immunosuppression, and probably also improves mucosal barrier function.”

Production and Use of Hymenolepis diminuta Cysticercoids as Anti-Inflammatory Therapeutics

I was glad to read that I already have access to the most hopeful treatment for inflammation. I have to say that I tried a lot of supposedly anti-inflammatory treatments  and was quite disappointed with most. Turmeric lattes, green tea extract, probiotic capsules, licorice root tincture…  Personally, I don’t really want to buy any more supplements, except basic ones such as vitamin D, since I live in cold and dark Canada, and occasionally I take fish oil on days that I don’t eat seafood.

The idea behind helminthic therapy, on the other hand, is quite logical to me. It’s not a promotion of another one magical super inflammatory ingredient. The logic is that humans and certain helminths have evolved to co-exist in a symbiotic relationship and therefore our immune system has also evolved  to be modulated by molecules that helminths produce. Recent eradication of helminths in humans in developed countries could be resulting in a destruction of a beneficial symbiotic relationship and increase in rate of autoimmune diseases.

“Graph the data points, and the trend is unmistakable. Since the 1950s, rates of multiple sclerosis, Crohn’s disease, type 1 diabetes, and asthma have soared by 300% or more (1). Similar graphs depict concurrent spikes in hay fever and food allergies (2).”

“Prevalence of food allergy in preschool children is now as high as 10% in Western countries, but remains just 2% in areas like mainland China (). The number of new cases of type 1 diabetes (T1D) in Finland per year is 62.3 per every 100,000 children, compared with just 6.2 in Mexico and 0.5 in Pakistan (). Ulcerative colitis, a form of inflammatory bowel disease (IBD), is twofold higher in Western Europe than in Eastern Europe—6.5 per 100,000 people versus 3.1 per 100,000 ().”

In each of these disorders, either the immune system is overreacting to a trigger, such as pollen, peanuts, or pollution, or it’s attacking tissues it shouldn’t, such as beta cells in the pancreas in the case of T1D and in the intestines in IBD.”

News Feature: Cleaning up the hygiene hypothesis

 

Celiac disease, vitamin and mineral deficiencies, and a beef patty

I’ve done something today that I probably haven’t done for at least a year or more. I bought a beef patty. I felt very guilty because I don’t want to eat large mammals. Ideally I wouldn’t eat any birds or animals, but we have to make practical choices. From my experience, having celiac disease, I don’t absorb vitamins and minerals well. A chicken leg of 100 grams has approximately 6% daily value of cobalamin, 6% DV magnesium, 7% DV potassium, and 25% DV B-6. Without eating meat or fish, you could try to get vitamin B-6 from beans, also fortified cereals contain B-6. Here is the issue – with celiac you cannot eat most fortified cereals and breads since they are not gluten-free, also eating too many beans causes digestive problems. So I had to make a choice and about a year ago  I chose to eat seafood and poultry, but not mammals. My reasoning is that compared to chickens and turkeys, large mammals such as pigs and cows have more complex brains and nervous systems and therefore have more complex emotions and might suffer more during their short life in a cage at a factory farm. I have no proof of that, but I had to make a choice.

Unfortunately recently I had to make another choice to start eating red meat again. I was experiencing lethargy and noticed white bands on my nails. Some sources stated that white spots on nails could be a sign of zinc deficiency, while others indicated that there was no correlation. This did lead me to wondering whether I was getting enough zinc, selenium, and B vitamins from chicken and salmon. 100 grams of beef on average contain 43% DV (daily value) of B12, 20% DV of B6. Dietitians of Canada also list beef as top sources of zinc, 75 grams of beef containing 4.0 – 8.6 mg of the mineral (women need 8 mg per day).  Chicken is much lower in zinc, 1.3 – 2.2 mg per 75 grams. Salmon was not listed as it is not a good source of zinc, it contains about 0.64 mg per 100 grams. Some studies indicate that it’s harder to absorb zinc from a plant based diet, in addition to that my absorption may be worse due to gut inflammation caused by autoimmune disease.

With reduced intake of meat and increased intake of phytate-containing legumes and whole grains, movement toward plant-based diets reduces dietary iron and zinc absorption.

Moving Toward a Plant‐based Diet: Are Iron and Zinc at Risk?

zinc1

Why do we need zinc and what happens if there is a zinc deficiency? Zinc is found in cells throughout the body and is needed to make proteins and DNA. Zinc plays a role in cell division, cell growth, wound healing, and the breakdown of carbohydrates. It is important for the function of the immune system and also the senses of smell and taste.

zinc2

Zinc deficiency can cause appetite loss, poor immune system function, diarrhea, eye and skin lesions, feeling lethargic, strange taste sensations, hair loss, weight loss, poor wound healing. Individuals with chronic conditions and poor absorption are more likely to be zinc deficient.

Zinc performs its biochemical functions as a divalent cation (positively charged ion) primarily when bound to enzymes and other proteins. Zinc is essential as a catalytic, structural, and regulatory ion and is involved in homeostasis (the tendency to maintain a stable, relatively constant internal environment), immune responses, oxidative stress, apoptosis (the death of cells which occurs as a normal and controlled part of an organism’s growth or development), and aging. Zinc is recognized as being important for stabilizing DNA and appears to reside in the nucleus longer than any other cell compartment. Therefore, it is possible that as intracellular levels of zinc increase, more iron will be displaced from nucleoproteins and less OH-driven DNA damage will occur.

Biological consequences of zinc deficiency in the pathomechanisms of selected diseases

A study on zinc deficiency in relation to psychiatry:

“Zinc participation is essential for all physiological systems, including neural functioning, where it participates in a myriad of cellular processes. Converging clinical, molecular, and genetic discoveries illuminate key roles for zinc homeostasis in association with clinical depression and psychosis which are not yet well appreciated at the clinical interface. Intracellular deficiency may arise from low circulating zinc levels due to dietary insufficiency, or impaired absorption from aging or medical conditions, including alcoholism. A host of medications commonly administered to psychiatric patients, including anticonvulsants, oral medications for diabetes, hormones, antacids, anti-inflammatories and others also impact zinc absorption. Furthermore, inefficient genetic variants in zinc transporter molecules that transport the ion across cellular membranes impede its action even when circulating zinc concentrations is in the normal range. Well powered clinical studies have shown beneficial effects of supplemental zinc in depression and it important to pursue research using zinc as a potential therapeutic option for psychosis as well. Meta-analyses support the adjunctive use of zinc in major depression and a single study now supports zinc for psychotic symptoms.”

The Emerging Role for Zinc in Depression and Psychosis

From my own experiment with N=1, I did feel better after eating a beef patty. This could be a coincidence, a placebo effect, or an actual effect of the minerals/vitamins in beef on my mood. I also thought of a substitute for beef that is not a mammal – mussels and clams. A 3-ounce serving of cooked mussels contains about 15% of daily value of zinc. The same amount of moist-cooked clams also provides 15% of the daily value for zinc. Clams and mussels contain high amounts of vitamin B12, selenium, and iron, as well as omega-3 fats. I think therefore it’s possible for me to continue avoiding beef if I include chicken, fish, mussels, and clams.

Depression and TSH levels

I continue to track my thyroid hormone levels and thyroid antibody levels. As my endocrinologist predicted, after a thyroid inflammation event (as indicated by ultrasound test results), and a state of hyperthyroidism, my thyroid hormone levels went the opposite way and now I am hypothyroid. I will say that for me personally the hyperthyroid state did not feel as bad as the current hypothyroid state, though I am hopeful that hypothyroidism can be treated with levothyroxine, which was recently prescribed to me. My antibody levels continue to be high and my endocrinologist stated that with Hashimoto’s autoimmune disease in general antibody levels stay chronically elevated. I might be receiving IVIG treatment soon, in April, and hopefully that will reduce the inflammation of the thyroid.

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In terms of emotions, during hyperthyroidism, I did feel jittery and very hungry, but I also experienced a roller coaster of more positive emotions such as more interest in men, infatuation, desire for adventure. I can’t say that my depression went away, but I do remember having moments of making plans to travel to Guatemala to attend a Spanish course, thinking of having an affair, wanting to perform in a band with my violin. Recently with hypothyroidism, as I described in a previous post, what I had been feeling is complete disinterest and grief. As if your life is somehow passing by, the world keeps going without you. There is a feeling of slowness in your movements and speech, a sense of painful emotional weight, inability to fully engage in an activity. Well if you have experienced hypothyroidism, you might know what I’m talking about. It’s feeling lonely and yet having no energy to call someone to make plans. Thinking that in theory I do enjoy playing violin, but today doing that would be just too difficult. Exercising definitely was becoming impossible, my legs have been feeling very heavy, and my whole body in general.

Today I started levothyroxine 0.025mg and I am hopeful that this will lower my TSH and therefore relieve all the symptoms that I am experiencing, at least I am very hopeful that levothyroxine in combination with IVIG will really help. I found an interesting study in which the authors seek a TSH threshold for depression. Two thirds of the study participants were female, as expected. There were 174 hypothyroid patients who were receiving levothyroxine treatment and were considered euthyroid. “Individuals who had developed euthyroid state under treatment with levothyroxine with TSH levels of 0.5–5 MIU/L with no need for dosage change were included in the study. After comprehensive history taking, laboratory tests including TSH, T4 and T3 were performed. Beck depression questionnaire was completed for all patients by trained interviewers. TSH cut-off values based on depression was determined by Roc Curve analysis.” Basically, as I understand, the researchers wanted to find out whether there is correlation between TSH levels and depression for patients who were diagnosed with hypothyroidism and are receiving levothyroxine.

Results were the following: “According to Roc curve analysis, the optimal cut- off value of TSH was 2.5 MIU/L with 89.66% sensitivity. The optimal TSH cut- off based on severe depression was 4 MIU/L. The present study suggests that a clinically helpful TSH cut-off value for hypothyroidism should be based on associated symptoms, not just in population studies. Based on the assessment of depression, our study concludes that a TSH cutofff value of 2.5 MIU/L is optimal.” I think what they are trying to say here is that based on large population studies there was a range for normal TSH levels determined, for example on my lab tests that range is stated as 0.32 – 4.00. Their study shows though that even though my individual TSH could be within this range, it doesn’t mean that I won’t be having any hypothyroidism symptoms, such as depression. Maybe for me personally TSH of 3.80 would be too high and my mood would be influenced and I would be better off at a level of levothyroxine that would bring my TSH below 2.5. Therefore it’s important to consider the symptoms of a specific patient and not just the determined ‘normal’ range.

TSH cut off point based on depression in hypothyroid patients

Also different countries and labs don’t state the same ‘normal’ ranges. In the study the TSH range is indicated as 0.5 – 5 MIU/L, while my lab states 0.32 – 4. So if I went to a doctor in another country, he could have said that my thyroid hormone levels are normal, but based on my lab’s range, my endocrinologist said that I might be becoming hypothyroid, since TSH is out of range, and therefore prescribed me levothyroxine. Also he did take into account the symptoms that I was experiencing, which is what the authors suggest – don’t just look at the TSH, how does the patient feel?

 

Planks, gut health, and mental health

I’ve had many conflicts with my father, but one thing I’ve always agreed with him on is that there is no mental health without physical exercise. Especially for those with emotional instability like me, I find that exercise is a necessity. It’s definitely not easy to do it with an autoimmune disease since sometimes after I get home from work – I feel lethargic, or I feel arm pain, or I feel isolated and a need to go on Facebook and see that people are alive. Well this is where logical thinking comes in – in the end choosing to exercise has the best payoff even though it’s not immediate. Lying down on the sofa and turning on Netflix has an immediate pay off, but if this is what I will do daily after work, after a while I will be worse off.

Currently I am trying to exercise two to three times a day. I do about 10-12 minutes before leaving for work in the morning, I include stretching, planks, downward dog, inversion poses, etc. Recently there have been some articles about positive impact of even very short intervals of exercise. I would like to believe that these statements are true as I am not able to force myself to wake up another twenty minutes earlier and engage in a 30 minute work out before work or breakfast. I do believe that some exercise is better than no exercise. I work in a boring office, so my hours are pretty standard. During lunch I walk around listening to a podcast and currently I signed up at a yoga studio located in the office building downstairs, which offers lunch classes. In the evening I try to do another 20-30 minutes of exercise. Is this exercise plan difficult? Yes, but once you do it several days in a row, I feel that there is some kind of adjustment and you get used to the schedule. Also I find it easier when I know that my exercise interval is only 12 or 20 minutes, I am not trying to push myself into an hour jog. In fact I don’t jog at all. I mentioned this before – one psychiatrist with whom I had a consultation stated that the best way to combat inflammation is exercise and that I should only do the type of exercise that I like, otherwise I will not stick with the routine for long. Therefore no jogging for me, I am doing planks and yoga poses.

The latest research shows that a single 10-minute bout of very light (30% of VO2 Max) physical activity can increase the connectivity between brain regions linked to memory formation and storage.

This potentially groundbreaking study on the cognitive benefits of short periods of mild exertion activity (such as gentle yoga, tai chi, slow dancing, or playing bocce) was conducted by researchers at the University of California, Irvine (UCI) and the University of Tsukuba in Japan.

Ten minutes of mild exercise may improve brain connectivity and enhance memory

From the abstract of the actual paper: ” A single 10-min bout of very light-intensity exercise (30%V˙O2peak) results in rapid enhancement in pattern separation and an increase in functional connectivity between hippocampal DG/CA3 and cortical regions (i.e., parahippocampal, angular, and fusiform gyri). Importantly, the magnitude of the enhanced functional connectivity predicted the extent of memory improvement at an individual subject level. These results suggest that brief, very light exercise rapidly enhances hippocampal memory function, possibly by increasing DG/CA3−neocortical functional connectivity.

Rapid stimulation of human dentate gyrus function with acute mild exercise

I now have some evidence to support my belief that my 10 minute work-outs are useful. Sometimes at work I do yoga poses in the staircase, or run up ten flights of stairs. There are many ways to exercise for free, it’s not necessary to purchase a monthly gym membership or pay $20 for a yoga class.

Some studies also indicate that exercise positively modifies gut bacteria. This change in turn can reduce inflammation and depression.

Recent studies suggest that exercise can enhance the number of beneficial microbial species, enrich the microflora diversity, and improve the development of commensal bacteria.

Collectively, the available data strongly support that, in addition to other well-known internal and external factors, exercise appears to be an environmental factor that can determine changes in the qualitative and quantitative gut microbial composition with possible benefits for the host. In fact, stable and enriched microflora diversity is indispensable to the homeostasis and normal gut physiology contributing also to suitable signaling along the brain-gut axis and to the healthy status of the individual. Exercise is able to enrich the microflora diversity; to improve the Bacteroidetes-Firmicutes ratio which could potentially contribute to reducing weight, obesity-associated pathologies, and gastrointestinal disorders; to stimulate the proliferation of bacteria which can modulate mucosal immunity and improve barrier functions, resulting in reduction in the incidence of obesity and metabolic diseases; and to stimulate bacteria capable of producing substances that protect against gastrointestinal disorders and colon cancer (such as, SCFAs).

Exercise Modifies the Gut Microbiota with Positive Health Effects

From ScienceDaily – “Two studies — one in mice and the other in human subjects — offer the first definitive evidence that exercise alone can change the composition of microbes in the gut. The studies were designed to isolate exercise-induced changes from other factors — such as diet or antibiotic use — that might alter the intestinal microbiota.”

Exercise changes gut microbial composition independent of diet, team reports

I think it’s very crucial to our mental health to exercise daily in any way – on a yoga mat at house, running up the stairs at work, going out for a jog, dancing, playing ping-pong, jogging with your dog, anything really that replaces sitting.