Some say Lion's Mane mushroom is the Jungle's King in fighting neurodegenerative diseases

Very recently, an incredible docuseries debuted on Netflix. It covers the highly interesting world of Fungi, their emergence as kings of the ecosystems, debunking the public generalised idea of an apparent vulnerability. We couldn't be 'more wrong'!!!! If there is a resilient species, clever for their societal dynamics, incredibly adapted to making their presence noticed with the sporulation of millions of very light microspores that get carried away by the weakest breeze, FUNGI are the deal. I wouldn't be able to reduce their tenacity and biological cleverness in a small book, let alone a paragraph in a blog post. 

Please watch the series 'Fantastic Fungi' (hopefully the link will be available for the years to come for everyone to savor the educational quality of its content).

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Fungi are very adaptable and in the game of survival that all species play for their own sake, they went from absurdly evolved underground networks to making other species do exactly what they want; a process as bizarre as the morbid zombie-like approach I have written about in a previous post entitled 'Survival of the Poisonous: "Ophiocordyceps vs. Ant'.

Nevertheless, a particular species of mushrooms that immediately caught my attention was the one known as Lion's Mane (Hericium erinaceus). This mushroom has been identified as having very interesting properties that can help solve, once and for all, the most challenging aspects of the neurological decadence in humans, especially those related to Alzheimer's. In a time where researchers try their very best in gathering the most clinically relevant information concerning this disease, and where predictors of incidence in humans are now starting to emerge from these research projects (like the one from the Lund University [1] that might help tackle the price and diagnosis' limitations that see around 20 to 30% of patients with Alzheimer’s disease ending up wrongly diagnosed even within specialised healthcare [1]. The project lead by Professor Oskar Hansson generated a prototype online algorithm that makes use of the combination of a simplified blood test ('measuring a variant of the tau protein [phosphylated tau] and a risk gene for Alzheimer’s') associated to a short (~10 minutes) triplet of cognitive tests. Alongside the simplicity of the process, especially when considering how challenging these patients can be when facing complex tasks, is the fact that the diagnosis predicts correctly with over 90% certainty exactly which patients would be in risk of developing dementia due to Alzheimer’s disease within a period of four years. 

This tool will not only increase the quality of care of patients in a predictive and planning fashion, but also concentrate and focus the targeting of the different developed drugs in more accurate indicators and variables, treatment-wise.

It is here, when it comes to treatment, that some researchers have been interested in the incredible potential that Lion's Mane Mushroom is reporting from the different investigational projects around the globe. For example, some investigators have observed this mushroom to have therapeutic properties that promote recovery of nerve and brain health [2] due to its erinacine production in the mycelia of its organism. The same authors even propose an optimised process for an advantageous fermentation process, so the content in erinacine A (the only erinacine substance that has been confirmed as having pharmacological activity in the central nervous system in rats) is increased [2]. Their rat models have helped identify protective properties in Ischemic Stroke (showing capacity to reduce neuronal apoptosis and stroke cavity size in the studied rat brains), Parkinson's Disease (a disease with a profile of gradual loss of dopaminergic cells in the substantia nigra pars compacta region of the brain, and that ultimately ends up resulting in motor problems such as 'resting tremor, rigidity, bradykinesia, and postural instability') - however, with Lion's Mane erinacine A, the dopaminergic injuries and accumulated oxidative stress in the stratum and substantia nigra were significantly improved. And even with transgenic rat-models of Alzheimer's disease where the occurrence of amyloid-β plaques that participate also in the increasing of secondary brain comorbidities such as 'inflammation, excitotoxicity, and apoptosis', and add on to the negative effects associated to the deposition of hyperphosphorylated tau proteins - in this study the observed transgenic mice treated with H. erinaceus mycelia were able to 'recover behavioral deficits after 81 days of administration'.

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The range of protective/recovering activities observed in the brain of different transgenic mice mimicking the different aforementioned neurodegenerative complications, reveal a promising way forward, as some studies have recently established:

Li, I-C. et al 2020 with the 'Prevention of Early Alzheimer’s Disease by Erinacine A-Enriched Hericium erinaceus Mycelia Pilot Double-Blind Placebo-Controlled Study' studied the effects of capsules containing two contrasting concentrations (350 mg/g and 5 mg/g) of erinacine A per day in treating mild Alzheimer's patients and observed that the highest concentration is well-tolerated and beneficial to their neurocognition.

Their cytotoxicity has already been established a long time back as low by other studies, I hereby mention solely two as an example to avoid a longer text [3] [4]; but this study by Li et al (2020) [5] where a 70-fold higher concentration has been used without observed clinical cytotoxicity is ever so promising for the future paths this realm of investigation may take.

Post picture kindly taken from https://www.healthline.com/nutrition/lions-mane-mushroom.

[1] Simple Diagnostic Tool Predicts Individual Risk of Alzheimer’s, Neuroscience News, [https://neurosciencenews.com/individulaized-alzhiemers-risk-tool-18484/], last visited on the 3rd of August 2021, last update on the 24th of May 2021

[2] Li, I-C., Lee, L-Y., Tzeng, T-T., Chen, W-P., Chen, Y-P., Shiao, Y-J., Chen, C-C. (2018). "Neurohealth Properties of Hericium erinaceus Mycelia Enriched with Erinacines". Behav Neurol. 2018.

[3] Mori, K., Inatomi, S., Ouchi, K. et al. (2009). "Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial". Phytother Res.; 23: pp. 367–72.

[4] Nagano, M., Shimizu, K., Kondo, R. et al. (2010). "Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake". Biomed Res.; 31, pp. 231–7.

[5] Li, I-C., Chang, H-H., Lin, C-H et al (2020). "Prevention of Early Alzheimer’s Disease by Erinacine A-Enriched Hericium erinaceus Mycelia Pilot Double-Blind Placebo-Controlled Study". Front. Aging Neurosci.; 12 (155), pp. 1-13.

What are 'The effects of plant-based diets on pancreatic beta-cell function'? - Part 2 of 2

On the second part of this analysis I would like to focus entirely and immediately on the study findings rather than dwelling too much on the strengths, limitations and possible confounders of the same. Anyone can read the paper and become aware of where further necessary investigations should go to account for reducing the limitations of this study, enhancing their strengths and rid of possible unnecessary confounders.

The results obtained in the study by Janko et al., 2021 objectivates certain information that, even though could and is also directly and indirectly related to additional variables, since the body is a holistic system, do attribute value to the plant-based diet in managing glycaemia:

1) The review used three randomised controlled trials which immediately offers an unbiased perspective on the study populations as it intends to account for significant heterogeneity between the different applied trials. However, the author is clear on a decision to not performing a meta-analysis that could have made the identified observations far more robust, but being allegedly the first systematic review covering this topic, a meta-analysis would be almost impossible, ergo the decision to not opt for such, I suspect. I assume I was not entirely sure that this was the reason behind the researcher's decision so I contacted my friend who confirmed that a meta-analysis was not a valid option 'because the individual studies weren't comparable, and didn't use the same intervention or biomarker". Makes perfect sense and it's a sensible decision.

2) The authors also observed that 'glycaemic control and beta-cell function, as measured by insulin secretion, can be improved by a plant-based diet' and that insulin synthesis pertaining to the period after dinner or lunch 'was significantly higher after a vegetarian burger compared with a meat burger' something that derives directly from a referred study by Kahleova et al, 2019 [1]. 

3) The reference normal levels of C-peptide (the endogenous pancreatic substance that informs one of the insulin secreted concentrations) in people without diabetes sits between 0.5-2.7 ng/mL. The observed reductions (see Kahleova et al, 2018) [2] of 0.5 ng/mL in fasting levels is  obviously  a medically significant one, especially when compared with an increment of around ~19-20% (0.5 ng/mL) (a possible indication of hyperinsulinaemia, as the authors infer from results obtained with the control group).

4) The reduction in glycated haemoglobin [HbA1c - see part 1 for more information on this indicator) 'at 24 weeks' as observed by Kahleova et al, 2011 [3] was also understood by the authors as clinically significant when compared to the control group. 'HbA1c levels and a reduction in diabetes medications may not be a direct measure of beta-cell function, but they are certainly a measure of glycaemia and diabetes management, and the plant-based diet groups experienced improvements in both measures in this trial'.

If you are interested in reading the first part of this post, please access HERE.

[1] Kahleova, H., Tura, A., Klementova, M. et al (2019). "A plant-based meal stimulates incretin and insulin secretion more than an energy - and macronutrient-matched standard meal in type 2 diabetes: a randomized crossover study". Nutrients, 11: 486.

[2] Kahleova, H., Tura, A., Hill, M. et al (2018). "A plant-based dietary intervention improves beta-cell function and insulin resistance in overweight adults: a 16-week randomized clinical trial". Nutrients, 10: 189.

[3] Kahleova, H., Matoulek, M., Malinska, H. et al (2011). "Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with type 2 diabetes". Diabet Med, 28: 549–59.

What are 'The effects of plant-based diets on pancreatic beta-cell function'? - Part 1 of 2

My good friend Robert Janko has published a systematic review on a very relevant topic for all of us in this day and age, especially because diabetes is still a recurrent topic for any age section, but also because vegetarianism has been the preferred punchbag for so many deniers out there; as if vegetarianism or veganism (perhaps fomented by the extremism of hipsters and their counterparts) was the monster who came to take over and impose, rather than just offer an optional view for a better life.

Robert researched intensively and published his findings in the Journal of Diabetes Nursing this year. The topic is ever so crucial and definitely adds on to the formula looking to partially contribute to the understanding of obesity, dietary habits, lifestyle behaviours and the row of physiological impairments caused by 'acquired' diabetes type-2. Plant-based diets have been linked to the betterment of blood glucose levels, glycated haemoglobin (complex of glucose + haemoglobin = HbA1c) levels, as well as improvements in insulin resistance. Through a systematic review of results obtained by three different clinical trials, Robert was able to show that, with intra-identified limitations, non-plant diets do not contribute as effectively as plant-based diets to a better controlled insulin secretion (healthy pancreatic beta-cell functioning) and weight loss.

But prior to jumping to the most relevant findings identified in Robert's review, it is important to define a few basic concepts beforehand. This will help us to better recognise, in a simple manner, the different implications of both diets in the human physiological system. The first question we should ask ourselves is...

Why is insulin secretion levels so important to one's health?

The higher the levels of HbA1c the greater the risk of developing diabetes-associated comorbidities [2]. If diet is directly or indirectly promoting higher levels of Hb1Ac then going back to the source and tweaking the physiological iterations, is a smart approach. For a healthy individual the levels of Hb1Ac should be below 42 mml/mol [2] and a slight change in obtained levels of glycated haemoglobin can have a huge impact even for people already diagnosed with Type-1 or Type-2 diabetes. Good management of glycated haemoglobin can contribute to reducing the occurrence of microvascular issues in about 25% [2]. Imagine being able to actually control the body to a point where one avoids retinopathy (that can cause permanent blindness) and neuropathy (that can cause permanent nerve damage) [3]. In  a nutshell, holding in one's dietary habits the power to not only control obesity and the extraneous emotional and physical burden to it associated, but also avoiding cataracts, heart failure, diabetic nephropathy, and even worse, the need for amputation as a result of peripheral vascular disease [2]. Another huge factor that needs to also be taken into account is the insulin resistance syndrome marked by the irresponsiveness of different cellular tissues (such as the muscular, hepatic and adipose) to effectively using insulin [4]. Glucose is left 'hanging' in the blood stream, more insulin is needed by the body for the necessary uptake of glucose by cells, and consequently the pancreas will have to work more to produce even more insulin to get the blood glucose levels within a healthy range.

Why measuring glycated haemoglobin?

The response is simple and direct. Whilst blood glucose levels offer an idea of the glucose levels in our blood at a precise point in time, Hb1Ac levels offer a more robust idea of the issue since it delivers an average over a period of time.

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The second part of this post will dive deep into Robert's article in order to share observed conclusions. I hope you visit the blog to stay informed, and who knows, make an informed decision regarding your dietary habits.

[1] Janko, RK, Wilson, P., Nworie, C. (2021). "The effects of plant-based diets on pancreatic beta-cell function: A systematic review". Journal of Diabtetes Nursing, 25(2), pp. 1-7.

[2] Guide to HbA1c, Managing Blood Glucose, [https://www.diabetes.co.uk/what-is-hba1c.html#:~:text=HbA1c%20is%20a%20measure%20of,take%2C%20usually%20from%20your%20arm], last access on the 29th of March 2021, last update on the 15th of January 2019

[3] Mackay, JD and Page, MM (1980). "Diabetic autonomic neuropathy". Diabetologia, 18, pp. 471-478.

[4] Insulin resistance and Prediabetes, National Institute of Diabetes and Digestive and kidney Diseases, [https://www.niddk.nih.gov/health-information/diabetes/overview/what-is-diabetes/prediabetes-insulin-resistance], last access on the 29th of March 2021, last update on May 2018

Photo by Markus Spiske on Unsplash

Can this Devil operate miracles? On the anti-inflammatory potential of the harpagophytum procumbens (Devil's Claw)

The World Cup started a few days ago, Mr Kim has met Mr Trump and apparently we are postponing another global armed conflict. I guess we can say the devil is losing this battle and all because our awareness has been raised lately. We are gradually investing in empathy rather than media displays of vulgar superiority. Just help sort out the plastic epidemics by buying less plastic-wrapped products, by demanding a serious environmental consciousness from your wholesalers and from yourself, and we must have a dandy world to show our grandchildren.

Yeah, the devil must not have the upper hand. Unless, of course, we are talking about autoimmune diseases such as Sjogren's syndrome, Lupus, and the whole rheumatic paraphernalia.... and so on and so forth. When it comes to anti-inflammatory issues we must give the devil a chance. OK, now that those who are crazy religious freaks and do not listen/read 'til the end are already painting banners stating God hates homosexuals and bashing biological evolution theories, let's focus on the devil for a moment. But merely on its claw, the Devil's Claw (known by the botanists as Harpagophytum procumbens).

You know, I got one of those emails that is so paradoxical and disturbing (a bit like when Jesse Lee Peterson goes on TV rebranding racism) - bear in mind I haven't taken a stance here. This is not a political blog and I do not dispute idiosyncrasies unless I am asked my opinion on it. But on such occasion the email I was sent explained that this Devil's Claw was the Father of all Miracles and would really fix any Sjogren's, Lupus, Cushing's etc etc etc patients suffering with pain and inflammation to a degree that Hell would become a vast garden of scented flowers.

I had to search the web for articles that would clarify all my concerns and ease my doubts. I ended up finding a video on YouTube, by a certain Dr. James Meschino, that pretty much throws a flaming scare alarm on the lenient use of this plant. Hence, I decided to review a few articles just to be sure that this product can actually be used for treating certain autoimmune diseases with an inflammatory profile. Huge disclaimer here - please ALWAYS resort to your medical doctor or pharmacist for they are the ones who know about your medical history, and use this information for educational support (Each Case Is a CASE!).

In summary this Dr. Meschino states that in fact this native plant from South West Africa, Angola, Madagascar, Botswana, Zimbabwe, Namibia and Kalahari Desert - Devil's Claw - shows enormous anti-inflammatory potential. He says:

1) one of its active constituents is the harpogaside that is believed to be the agent responsible for counteracting inflammation;

2) due to its bitterness it stimulates acid release in the stomach promoting better protein metabolisation;

3) He advises on a quarter to half a gram, two to three times daily (an amount that will roughly correspond to about 5% in harpagoside content);

4) and that harpagosides are believed to hold powerful anticoagulant effects, and for that matter can reactivate or aggravate ulcers, thus should not be combined with other anti-inflammatories (non-steroidal or steroidal ones), nor with anti-coagulants (even if new generation ones). The risk is simple to understand and serious in its own nature - INTERNAL BLEEDING.

Pharmacological active molecules

Not all molecules show the same anti-inflammatory potential, as shown by Fiebich et al (2001) [1] who conducted a very interesting study using a Devil's claw commercial extract to inhibit lipopolyssacharides of bacterial nature. In fact, McGregor et al (2205) [2] also confirmed such, a few years later, when attesting the pharmacological/therapeutic potential of this plant, especially the role of the iridoid glicosides present in its list of constituents (namely harpagoside, procumbide, harpagide, and the 8-para-coumaroyl-harpagide). But warnings were simultaneously published as to the limitations imposed by the test models used.

Toxicity

Well, in regard to toxicity, al-Harbi et al (2013) [3] subjected mice to different official treatment protocols (as suggested by the World Health Organisation): The chronic toxicity study used 100 mg/Kg/day (representing 1/5 of the pharmacologically active dose) administered for a period of 3 months, and focusing on vital organ weight variation, external general symptoms of toxicity, and body weight changes and mortality (up to the end of the trials and not for long-term periods); and concluded that the subjected cohorts experienced low toxicity.

The same study also covered acute toxicity where the subjects were presented to oral doses (0.5, 1 and 3 g/Kg body weight) of the drug suspended in water. This time the analysis focused on autonomic responses, motor activity and central nervous system excitation. One interesting finding is related to 0.5 g/Kg treatment of Devil's claw that  significantly reduced blood glucose levels when compared to untreated cohorts.  However, these were merely preliminary studies and only point towards general assumptions for future studies to consider.

Applications in rheumatic diseases

The incidence of musculoskeletal disorders responsible for disabling many people's lives is high, and any possible natural treatments with pharmacological potential must be analysed for future remedies. Brien et al (2007) [4] compiled a review on the topic that pointed towards safe use of Devil's claw in comparison to non-steroidal anti-inflammatories in reducing pain associated to this disease. The same positive results were also supported by Warnock et al (2007) [5] that focuses their analysis on a number of rheumatic diseases (including arthritis) and a single group of 259 patients for eight weeks with tolerance, liver tests and blood analysis performed. But the main concern could not be answered to, meaning its safe use is still not guaranteed especially because there are no long-term safety assessments and the populations studied are quite limited in number.

Safety

Because I could not find many articles that supported the allegations of Dr. Meschino (I am not saying there isn't any, I am just saying I couldn't find that many) I am not going to say he isn't right. One think I am certain of is that the jury is pretty much still out there on the safety of this plant. But its pharmacological efficacy and range of applications is very much attested. Nevertheless, what the doctors suggest is almost common sense for when we are unaware of the mechanism of action [MOA], as it is the case for the Devil's claw herb, and the MOA of many other complementary and alternative medical therapies [6]. One thing is certain, because of its bitterness it will indeed affect stomach acidity, ergo affecting drugs like proton pump inhibitors, H2-blockers (also known as H2 receptor antagonists) and the like, used to reduce stomach acidity. This is the reason why it might be involved in the worsening of ulcers. However, the safety assessments I was able to find are limited in numbers of populations studied and even range of observations performed. Having said that, I found a really nice piece of document that is 69-pages long, written by the European Medicines Agency [7] (access here) that I will eventually read and try and summarise for you. Bear in mind this document covers many different aspects like medicinal application of this plant, to clinical and non-clinical data, clinical safety, pharmacovigilance aspects and what interests you the most, being the risk-benefit assessment. Once again, after a very brief reading (not thorough at all) I could only find a drug interaction study [8] supporting the allegations of Dr. Meschino, but I still have to lay my eyes properly on this document. The article by Patel et al (2008) [8] apparently (as I could not pay for it, but if you want me to read it just be my guest and send me the money :DDDD) suggests putative interactions with anticoagulants (e.g. warfarin) leading to gastrointestinal bleeding. There was also another article I found (access here) [9] but with no listed authors or free-PDF available that suggests that, in practice reports and concerning devil's claw roots exposed-patients, some showed up with upper gastrointestinal disorders.

The jury is pretty much out there as I already said, but I am sure I will have to discuss the topic further in the weeks to come. Until then, play it safe.

[1] Fiebich, B. L., Heinrich, M., Hiller, K. O., Kammerer, N. (2001). "Inhibition of TNF-alpha synthesis in LPS-stimulated primary human monocytes by Harpagophytum extract SteiHap 69". Phytomedicine, 8(1), pp. 28-30.

[2] McGregor, G. Fiebich, B., Wartenberg, a., Brien, S., Lewith, G., Wegener, T. (2005). "Devil's Claw (Harpagophytum procumbens): An anti-inflammatory herb with therapeutic potential. Phytochemistry reviews, 4(1), pp. 47-53.

[3] Al-Harbi, N. O., Al-Ashban, R. M., Shah, A. F. (2013). "Toxicity studieson Harpagophytum procumbens (devil's claw) capsules in mice". Journal of Medicinal Plants Research. 7(42), pp.3089-3097.

[4] Brien, S., Lweith, G. T., McGregor, G. (2007). "Devil's Claw (Harpagophytum procumbens) as a treatment for osteoarthritis: a review of efficacy and safety".  The Journal of Alternative and Complimentary Medicine, 12(10).

[5] Warnock, M., McBean, D., Suter, A., Tan, J., Whittaker, P. (2007). "Effectiveness and Safety of Devil's Claw tablets in patients with general rheumatic disorders". Phytotherapy Research, 21(12), pp. 1228-1233.

[6] Setty, A. R., Sigal, L. H. (2005). "Herbal medications commonly used in the practice of rheumatology: mechanisms of action, efficacy and side effects". Seminars in Arthritis and Rheumatism, 34(6)pp. 773-784.

[7] Assessment report of Harpagohytum procumbens DC. and/or Harpagophytum zeyheri Decne, radix. [http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_HMPC_assessment_report/2016/11/WC500216100.pdf]

[8] Patel, J. A., Gohil, K. J. (2008). ""Warfarin-herb interactions: a review ad study based on assessment of  clinical case reporsts in literature". Boletin LatinoAmericano y del Caribe de Plantas Medicinales y Aromaticas, 7(2), pp. pp. 85-99. [https://www.scribd.com/document/293374607/Warfarin-Vitamin-K-Patel-2008]

[9] No authors listed (2013). "Devil's Claw root: Ulcers and gastrointestinal bleeding". Prescrire Int, 22(144), pp. 296. [https://www.ncbi.nlm.nih.gov/pubmed/24600731]

1st image kindly taken from Harpagophytum procumbens - diseases, [http://flipper.diff.org/app/items/6532], last visited on the 18th of June2018.

2nd image kindly taken from Kew, Royal Botanic Gardens, [https://www.kew.org/science/news/plant-story-devils-claw-found-and-collected-from-botswana], last visited on the 18th of June 2018.

On the health benefits of Pimenta racemosa

A reader (Lary Hirabedian) left me with a question as a comment "On the allergenic potential of bay leaf" about two months ago. I have been so busy with work and my children that it was almost impossible to dedicate any time whatsoever to researching properly and responding to Lary. He asked me if I could comment on Pimenta racemosa vs bay laurel, i.e., establishing a comparative efficacy, health benefits against, for example, cholesterol reduction, diabetes, pain reduction, antiviral and antibacterial effects, etc. He also suggested that Pimenta racemosa in the shape of oil or infusion can be more effective than bay laurel.

I'd like to reinforce that I am not a plant biotechnologist and I am not a plant physiologist, actually I am quite far from enjoying the study of plants per se. My interest lays on the different substances that exist in the world (plant, animal or inorganic) as a scientist interested in those that have a toxicological potential or health benefit to all of us. Having said that, I think I'd like to contribute with a few lines to help responding to this question without presenting a dispute between these two plants. I prefer to provide you with what is out there, literature-wise, concerning the different molecules present in Pimenta racemosa.

But to start with, let's try and understand exactly what plant are we talking about. Pimenta racemosa is the scientific name for the plant that is commonly known as Bay-rum tree, others call it malagueta, and I am sure other people worldwide call it different names for this plant is quite widespread through Asia and Africa. The plant belongs to the Myrtaceae family and is famous for its essential oil with 'alleged' curative properties. That is what we will try to unfold in the coming lines.

In the article by Contreras (2014) [1] one can find a long list of different research studies on the  putative pharmacological effects and biochemical agents of the different Pimenta species, like for example the capacity to repel insects and its mosquito larvicidal and nematicidal properties, the capacity to reduce/inhibit pain (for example pain associated to dysmenorrhea), anti-inflammatory effects (possibly due to flavonoids, tannins, polyphenols), the capacity to counteract fever (possibly due to quinones), antimicrobial properties (e.g., flavonoids, tannins, triterpenes, steroids), antioxidant properties (e.g., flavonoids, saponins, polyphenols), antimutagenic effects (e.g., flavonoids, tannins, saponins), as an antidote against cobra venom and so on and so forth to a very detailed biochemical level. It is just a matter of getting that article and read thought the other references for the specific effect one is trying to learn more about.

Another very composed article [2] identified 52 components (where 1,8-cineole was the major one) present in the flower itself of this plant, after gas chromatography assays.  But the most interesting observation I could personally identify in this article was the cytotoxic activity against a panoply of human cell lines and the antimicrobial activity against Geotrichum candidum and bacillus subtilis - part of the human microbiome, and where the identified minimum inhibitory concentration  [MIC] is exactly the same as for the common antibiotics applied against these bacteria, Ampicillin and Amphotericin B, respectively. Actually, this article is a great add-up to the Alitonou et al (2012) [3]  where essential oils compositions of Pimenta racemosa from two different sites in Benin were studied thus unveiling the same antimicrobial, antioxidant and even acaricide properties, but only this time no anti-inflammatory effects were recognised.

In fact, great literature is starting to emerge on this topic and it is just a matter of looking in the right articles for gaining the adequate knowledge. Finally, the food industry will definitely want to look into this essential oils for its antioxidant properties, as well as the phamaceutical industry into all the different pharmacological effects identified.

Image kindly taken from Plantogram, Leon Bay Rum Tree, [https://plantogram.com/product/bay_rum_lemon/], last visited on the 10th of April 2018, last update unknown.

[1] Contreras, B. (2014). "Preliminary phytochemical screening of pimenta racemosa var. racemosa (Myrtaceae) from Tachira - Venezuela". Pharmacologyonline, 2, pp. 61-68.

[2] Al-Gendy, A. A., Moharram, F. A., Zarka, M. A. (2017). "Chemical composition, antioxidant, cytotoxic, and antimicrobial activities of Pimenta racemosa (Mill.) J. W. Moore flower essential oil". Journal of Pharmacognosy and Phytochemistry, 6(2), pp. 312-319. 

[3] Alitonou, G. A., Noudogbessi, J-P., Sessou, P. et al (2012). "Chemical composition and biological activities of essential oils of Pimenta racemosa (Mill.) J. W. Moore from Benin". International Journal of Biosciences, 2(9), pp. 1-12.

Candidiasis and Sjogren's

Two things that really piss me off and work my nerves: lazy people that send corporate emails signing only with their first name's initial (guys, honestly, C can be both for Charlie as for Cu... Cummings, so how do you prefer to be called?), and Candidiasis. Yeah, you read right, Candidiasis.  For those less alert Candidiasis has been with us humans for a long time now, and it is dead annoying.

Be it in the shape of an oral thrush, vaginal thrush or the typical Athlete's foot, these fungal infections manifested by the overwhelming presence of the organism Candida albicans, is a resilient sucking microorganism. This fungus does not have segregationist issues, it just goes for anyone and everybody as you see in the accompanying picture. Baby bottoms, men's toenails, woman's vaginal canal, mouths, feet, knees, tongues, it just predates from everywhere if it is given the chance.

Like Interstellar so well portraits in the big screen, one day our beautiful world as a result of our incredible selfishness and stupidity will allow these hyper-collaborative hyphae to forage and eliminate everything as it passes through.

For those affected with certain autoimmune issues, like Sjogren's syndrome patients, candidiasis is a daily battle and one that usually the organism just rubs off their shoulders. Easy-peasy, they win, no biggie!

If you read the fantastic 1980's article by Jones et al [1], you immediately understand that the prevalence of Candida albicans in the intraoral moiety in Sjogren's syndrome is not a joke. Even though the sample population is short I can assure you that it is so significant that it can be almost immediately extrapolated further. 

Because Sjogren's syndrome is marked by a connective tissue disorder, the establishment of Candida albicans associated to low salivary pools (no mechanical flush of the fungus) and the absence of secretory immunoglobulin IgA (the major antibody present in saliva) provides the appropriate environment for proliferation. Jones et al observed that in comparison to healthy controls the ratio of infection density could reach to more than 4-fold higher in areas such as the anterior and posterior tongue, floor of mouth, right cheek, anterior palate, upper denture, right commisure, lower denture, anterior labial sulcus, posterior palate and left commisure.

Add all that to the fact that this fungus is azole-resistant, meaning that antifungal resistance for them is a joke, they 'thrive' on it! Affected individuals have then to resort to domestic remedies because the pharmaceutical weaponry is not making it for them. Some resort to diets rich in apple cider vinegar, coconut oil, cruciferous, ginger, etc etc etc... and remove sugar all together. That arrests the growth of the fungus. Some apply peeled onion to the affected areas which personally I can assume it relieves the hitching for a few days, but does not erase the problem. What can actually reduce the prevalence of Candida albicans is a strict rigid responsible and disciplined attitude where all the bad foods become prohibited and the good ones are for compulsory ingestion. 

Because I don't like to get my hands on stuff that is already excellent, quality-wise, I am not going to write down what you have to do, other people have done it already in the shape of a book I just bought. But I'll tell you where you can find a source of information that will definitely help you in this process - The Candida Diet [2].

Good luck and let me know if you made it. I'm definitely going to try it out. Now, I gotta go scratch my toe :P

[1] Tapper-Jones, L., Aldred, M., Walker, D. M. (1980). "Prevalence and intraoral distribution of Candida albicans in Sjogren's syndrome". Journal of Clinical Pathology, 33, pp. 282-287.

[2] 10 foods that will fight your Candida, The Candida Diet, [https://www.thecandidadiet.com/candida-fighting-foods/], last visited on the 28th September 2017, last update unknown. 

I have a question, or actually three... on bay leaf

Bay leaf and more bay leaf. A million questions...! 

It took me quite a while to find sometime to research on these matters. That, and the fact that I don't want to make this blog talk exclusively of bay leaf. There is loads of important toxicology issues to debate, inform and learn about; why focusing so much on bay leaf.

But the audience likes the topic, I like the audience, matching 2 and 2 together results in 3. Yes, today and only today 2+2 = 3 questions answered on bay leaf.

1) From an anonymous person who's asking us about the properties of bay leave for curing bunions. For those who aren't familiar with the term, a bunion is, according to the NHS website a 'bone deformity of the joint at the base of the big toe'. Considering that I'm no medical doctor and that any patient suffering with such ailment should definitely seek treatment with one, all I can say is that as a home-remedy I have not found scientific information on bay leaf curing bunions. Anecdotal reports??? Loads of them, they're all over the web and you can do with such information whatever you feel like. My personal advice is that for an issue that often derives from autoimmune complications, like rheumatoid arthritis, or emerges from genetic proneness traced back through one's family tree, a simple assessment is not the brightest approach. In addition, these websites base their results on bay leaf as drinking tea and oil as ointment, and on the anti-inflammatory properties of the plant itself. Bay leaves contain Eugenol that is a chemopreventive substance [1], meaning this chemical has the potential to inhibit/stop a certain disease process. In that sense, it might induce anti-inflammatory responses, like when one is afflicted with bunions. 

2) Lolo Gibbins, a reader of The Toxicologist Today, presented me with a very different question concerning the use of bay leaves to get rid of rats. I will not prolong this one request for long. Using specifically bay leaf as a pesticide against rats... or rodents... I never heard of. Not meaning it's impossible, but I never heard of. What I heard about is of a quite recent article by Chaudhary et al (2017) [2] that discusses the advances in the knowledge gained on the potential of Azadirachta indica (also known popularly as neem leaves  - post image) as a biopesticide. As you may know biopesticides also encompass rodenticides (a substance capable of killing rodents). It's worth reading. And if you are willing to pay me for the time invested, I can read  itand summarise it for you ;) 

3) And the last one comes from an unknown reader who have questioned me on if bay leaves combustion fumes are toxic for cats. My answer couldn't be blunter and humbler. I simply do not know and found no information whatsoever on the matter. Probably the best advice is indeed for the reader to revisit that post on the toxicology of burning bay leaf wood as a source of fuel that can be accessed HERE.

1) Hussain, A., Brahmbhatt, K., Priyani, A., Ahmed, M., Rizvi, T. A., Sharma, C. (2011). "Eugenol enhances the chemotherapeutic potential of gemcitabine and induces anticarcinogenic and anti-inflammatory activity in human cervical cancer cells". Cancer Biotherapy and Radiopharmaceuticals, 26(5), pp. 519-527.

[2] Chaudhary, S., Kanwar, R. K., Sehgal, A., Cahill, D. M., Barrow, C. J., Sehgal., R., Kanwar, J. R. (2017). "Progress on Azadirachta indica based biptesticies in replacing synthetic toxic pesticides". Frontiers in Plant Science, 8(610), pp. 1-13.

Post image kindly taken from Neem, Dr. Haushcka, [https://www.dr.hauschka.com/en_DE/knowledge-base/medicinal-plant-facts/neem/].

Closure to homoSOYxuality

I have been a vegetarian for 20 years now, give and take. I've had my share of soy in the meals I cook, and also in the ones I have in restaurants. So far I can assure you that I still feel the same man, i.e., deeply in love with my wife, still feel attracted to the opposite sex (especially to anyone looking like Jennifer Lawrence, Natalie Portman, Monica Belluci or Charlize Theron), no shrinkage of penis has occurred so far (you'll have to trust me on that for I'll never post any proof on Instagram :P, I don't even have an Instagram account), and I am not infertile (two beautiful babies so far, but I'm stopping there and it's not about the soy beans, it's really that now I need to enjoy the kids and travel with them, show them the world, the different cultures and diversities so they don't blame soy beans for male homosexuality in the future).

I understand the political stance played by a scapegoat decoy, but we must be truthful to the available scientific data collected thus far. The best practice is actually to kind of lightly x-ray the previously referred literature (see post here) and see exactly what was measured, what agents were scrutinised and reference levels suggested to produce significant alterations (reference to these articles can be found in the previous post). Let's start then:

"Altered sexualy dimorphic nucleus of the preoptic area (SDN-POA) volume in adult Long-Evans rats by dietary soy phytoestrogens"

A study using Long-Evans female and male rats where a Phytoestrogens-rich diet and a Phytoestrogens-free diet are put to test. There is a significant reduction in body weight and prostate weight observed, however, testosterone levels are not affected by the different diet treatments; and finally the Phytoestrogens-rich lifelong diet delays puberty onset without impacting on the cycle. The study does not check impact on humans and to be fair never intended to, but other questions we can distill are, for example, how many of us humans would indeed make a life based on phytoestrogens-rich diets? Most likely, no one. And how much phytoestrogens is too much? Where is the threshold? What other foods that make part of our diet also contain high levels of phytoestrogens, and what is a 'high level of phytoestrogens'???!

Again, this is not a judgmental analysis of the study, actually it's quite far from that, but instead a judgmental analysis of anyone using it as proof of soy impacting on human sexual maturation, per se.

"A soy supplement and tamoxifen inhibit sexual behaviour in female rats"

A study focusing on the patterns of sexual behaviour in rodents (rats) based on 'chemotrophism' triggered by progesterone and oestrogen. Diets containing different soy contents were studied as impacting agents on sexual mating behaviour a few hours after ingestion and analysed against a progesterone injection. Overall, the results indicated soy supplement as an oestrogen antagonist - bad news to certain people,  crude news in the overall picture -, but again, how much soy is too much, where's the threshold? I am not considering the study a limited one as to be fair it did study what was proposed in itself, but who can consider phenotypical/biochemical/endocrine changes to male biology simply based on these values? No one.

And to be fair I could go on and one with every single study discussed in the previous soy post, but it wouldn't take us anywhere. So I chose to discuss the hot topic, the one that really has been driving criticism against soy presence in diets go crazy, i.e., soy-based infant formulas.

"Safety of soy-based infant formulas containing isoflavones: The clinical evidence"

For starters, soy-based infant formulas provide a healthy alternative to those children who are lactose-intolerant. Moreover, they agree with the most strict regulatory and safety standards. A comparison study conducted at the University of Iowa, comparing between soy-based infant formula (SBIF) and human milk/cow's milk, and analysing mean weight in infants, resulted in no differences in the first 4 months of development. And a follow-up study of the adults who were fed either SBIFs or cow's milk showed that no differences were produced in their adult weight, for both males and females.

In terms of reproductive development the presence of isoflavones that some scientists attribute to impacting agents affecting sexual maturation stages of those fed with SBIFs, was also evaluated. But this article refers also other research articles written by intelligent people and not by lazy prophets of doom, that backup the complexity of extrapolating potential adverse effects (seen occurring in animal models) into the human biology.

I must quote the article on a few remarkable/excellent observations:

"...rodent studies investigating in utero exposure to isoflavones need to be interpreted in the light of the relatively lower estradiol levels in pregnant rodents compared with pregnant women. The fetal rat is exposed to picomole levels of estradiol whereas the human fetus is exposed to micromole levels of estradiol" [1].

"Fielden et al (2003) [2] studied the effect of gestational and lactational exposure to genistein on testicular weight and sperm quality in adult mice at levels comparable with or greater than human exposure. Results showed no significant treatment-related effects on male offspring body weight, anogenital distance, seminal vesicle weight, or testis weight. However, not all studies concur with these findings [3]". 

"In contrast, clinical studies showed that infants fed SBIF have normal reproductive development and later health. In an abstract, Businco et al (1999) [4] studied 34 children who had been fed SBIFs who were then evaluated at a median age 29 mo. A detailed physical exam included signs of sexual maturation and bone density, metabolic markers of bone, and one marker of estrogen. The investigators’ conclusion was that phytoestrogens in SBIFs did not induce hormonal effects".

And we could go on and on for weeks and get exactly the same feedback we have been comprising thus far. There isn't enough evidence that can suggest that phytoestrogens, to the levels that are fed to people, especially infants, can impact on sexual maturation. As to people turning gay because they are fed SBIF, what can I say???? Homosexuality has been among us since ever and now we need to blame soy for personal options??? What are people going to come up with next? That our politicians don't really want to corrupt, it's the air we breath that is making them selfish pricks?

Well, the judge is still out there for an eventual need to relate phytoestrogens to different sexual orientations. In terms of sexual maturation and aberrant sexual organs' development, we could very much blame parents for smoking, the tones of rubbish put into consumed meat, the completely makeshift foods that are sold in our supermarkets, the quality of our lives filled up with stress and anxiety, the incredible irrational intake of sugar and hydrogenated fats that are generating super obese newborns, the levels of lead that back in the 60s was present in the paint used in cradles and other furniture for children, or even the nail polish solvent ethyl acetate in toothpaste,  etc etc etc. 

I might bring up some hysterical/historical facts on that matter if you guys comment on this post and make me believe it's worth. See you soon and keep using soy, moderately as anything else... you wouldn't drink a whole cow would you? 

Bye!


[1] Clark, J. H. (1998) Female reproductive and toxicology of estrogen. Korach, K. S. eds. Reproductive and Developmental Toxicology 1998:259-276 Marcel Dekker New York.

[2] Fielden, M. R., Samy, S. M., Chou, K. C. & Zacharewski, T. R. (2003) Effect of human dietary exposure levels of genistein during gestation and lactation on long-term reproductive development and sperm quality in mice. Food Chem. Toxicol. 41:447-454.

[3] Wisniewski, A. B., Klein, S. L., Lakshmanan, Y. & Gearhart, J. P. (2003) Exposure to genistein during gestation and lactation demasculinizes the reproductive system in rats. J. Urol. 169:1582-1586.

[4] Businco, L., Bruno, G., Giampietro, P. G. & Furcolo, G. (1999) No oetrogens hormonal effects in long-term soy formula fed children. J. Allergy Clin. Immunol.103:S169.

Introduction to HomoSOYxuality

Every month I try my very best to get in touch with my relatives, especially now that I live over 985 miles from what used to be home. In one of those events I routinely label 'The Round', I call basically all my family (usually my aunts and grandma because I come from a very matriarchal family).  They love hearing from us, knowing about how the kids are growing so fast, their funny personalities, my day-to-day chores, how I've recently been threatened by a right-wing extremist in the middle of the streets, the good and the bad of a migrant's life. Some calls get to be super funny because one of my aunts always falls for my classic pranks where I play the role of a Brazilian salesman trying to get her to buy the newest internet package, or a Ukrainian construction engineer asking for a cab... I don't know why, but her naivety is so contagious that the whole family ends up laughing of her incapacity to recognise me amongst my million voices.

In one of those calls I ended up talking to my godmother. She is a secondary school teacher... I guess she is retired now, but the indoctrination spirit is still there, and quite alert! And she loves pharmacology in the 'hypochondriac' way. Well, not that she is a hypochondriac, I must say, but she knows basically everything a real hypochondriac needs to know to be a hardcore professional hypochondriac. 

And on that specific day she went on and on about stuff I am still trying to digest, advice after advice, nothing very technical or scientific in the data sense of the topic; but quite accurate, to say the least. It was all good until she started, like many other times in the past, complaining about my vegetarian options and my soy milk breakfasts. Straight away she told me she read somewhere, somewhen, that soy milk breakfasts end up giving you soy milk breasts... 'Do not feed that to your child, please avoid it'. I came to know that the web is filled with scare-articles about boys growing with reduced-size testicles and boobies so big they look like silicon implants. 

But what is in fact true about this new wave of articles relating soy (and its potent phytooestrogen daidzein - belonging to a group of isoflavones) to the appearing of female traits in male children? I had to investigate.

I immediately recalled having read an article, long time back, written by a redneck religious prophet bragging about soy being the cause of high homosexuality incidence rates in America. And when I read that article I honestly felt towards those prophets, like Albert Camus, when he once said:

But after, I realised that the best way to refute a secular supposed scientific preconception is by analysing the alleged scientific foundations that give roots to such false-belief. Could it be possible that there was a dash of scientific grounds to even remotely assume that soy consumption, due to its high oestrogen levels, can make you physically/behaviourally effeminate? I had to go straight to the scientific facts, the studies with no moral judgements from any third-parties whatsoever. I needed to make sure the assessed studies were based on physical and endocrine alterations and not a witch hunt everyone is already so sick of.

Study Title	Methodology and/or Goals	Relevant Endocrine/Physical observations
Altered sexually dimorphic nucleus of the preoptic area (SDN-POA) volume in adult Long–Evans rats by dietary soy phytoestrogens [1]	Animals were fed either a phytoestrogen-rich (Phyto-600) or a phytoestrogen-free (Phyto-free) diet. And also males or females fed the Phyto-600 diet (from birth) were switched to the Phyto-free diet.	Consumption of phytoestrogens via a soy diet, significantly: (1) decreases body and prostate weight, (2) delays puberty onset, and (3) alters SDN-POA volumes during adulthood.
A soy supplement and tamoxifen inhibit sexual behaviour in female rats [2].	Examined the impact of the selective oestrogen receptor modulator tamoxifen and a popular soy phytoestrogen dietary supplement on female sexual behaviour in rats. Ovariectomised female rats were given either tamoxifen or the soy supplement, then injected with oestradiol benzoate or oil (followed with an injection of progesterone) and tested for sexual behaviour after the progesterone injection.	Soy significantly attenuated paced mating behaviour in animals compared to controls acting as an oestrogen antagonist on female rats.
Safety of Soy-Based Infant Formulas Containing Isoflavones: The Clinical Evidence [3].	Discusses the available clinical evidence regarding isoflavones in soy infant formulas in relation to nutritional adequacy, sexual development, neurobehavioral development, immune function, and thyroid disease.	Available evidence from adult human and infant populations indicates that dietary isoflavones in soy infant formulas do not adversely affect human growth, development, or reproduction.
Oestrogens and phytoestrogens: brain plasticity of sexually dimorphic brain volumes [4].	Examined the consumption of phytoestrogen (using a phytoestrogen-rich versus a phytoestrogen-free diet) s from conception to adulthood (and shifting) to characterise (a) circulating plasma phytoestrogen levels, (b) testosterone levels in males, (c) sexually dimorphic brain volumes and (d) the presence of apoptotic cells in these brain structures in Long-Evans rats.	Consumption of dietary phytoestrogens can alter hormone-sensitive hypothalamic brain volumes in rodents during adulthood.
Changes in male reproductive system and mineral metabolism induced by soy isoflavones administered to rats from prenatal life until sexual maturity [5].	Determined the influence of high-dose soy isoflavones (daidzein and genistein) administered from prenatal life to sexual maturity on testosterone and oestradiol levels, testicular and epididymal morphology, the number of epididymal spermatozoa, and mineral metabolism in rats.	Relatively mild effects of phytoestrogen administration on the morphology of testes and epididymides and the number of epididymal spermatozoa were observed despite the high dose used.
Soy, phyto-oestrogens and male reproductive function: a review [6].	Examined the evidence regarding the potential detrimental effects of soy and phyto-oestrogens on male reproductive function and fertility in humans and animals.	Overall, there are some indications that phyto-oestrogens, alone or in combination with other endocrine disruptors, however, these results must be interpreted with care, as a result of the paucity of human studies and as numerous reports did not reveal any adverse effects on male reproductive physiology.

After analysing the overall observation of these carefully selected studies I came to the easy conclusion that there are so many latent questions to answer that it is almost impossible to do a proper job with a single post. Questions as simple as what can be considered a soy-rich diet, how much is too much for the human endocrine system, what daily consumption can be assumed to produce significant results, what exact indicators shift behaviour, and what is their significance in the holistic perspective of things?..., etc etc etc.

Like most of these articles suggest, the results need extreme care in their analysis and none favour a specific trend or school of thought. They are in need of yet a lot more data to actually impose anything conclusive. Therefore, I decided to give it yet another go. In the next post I'll be summarising the significant physical/endocrine/behavioural alterations that are indeed observed and described in the above mentioned articles.

***

[1] Lund, T. D., Rhees, R. W., Setchell, K. D. R., Lephart, E. D. (2001). "Altered sexually dimorphic nucleus of the preoptic area (SDN-POA) volume in adult Long–Evans rats by dietary soy phytoestrogens". Brain Research, 914(1-2), pp. 92-99.         

[2] Patisaul, H. B., Luskin, J. R., Wilson, M. E. (2004). "A soy supplement and tamoxifen inhibit sexual behavior in female rats". Hormones and Behavior, 45(4), pp. 270-277.

                       

[3] Merrit, R. J. and Jenks, B. H. (2004). "Safety of Soy-Based Infant Formulas Containing Isoflavones: The Clinical Evidence". The Journal of Nutrition, 134, pp. 1220S-1224S.

[4] Lephart, E. D., Rhees, R. W., Setchell, K. D. R., Bu, L. H., Lund, T. H. (2003). "Estrogens and phytoestrogens: brain plasticity of sexually dimorphic brain volumes". The Journal of Steroid Biochemistry and Molecular Biology, 85 (2-5), pp. 299-309. 

[5] Piotrowska, K. et al. (2011). "Changes in male reproductive system and mineral metabolism induced by soy isoflavones administered to rats from prenatal life until sexual maturity". Nutrition, 27(3), pp. 372-379.

[6] Cederroth, C., Auger, J., Zimmermann, C., Eustache, F., Nef, S. (2009). "Soy, phyto-oestrogens and male reproductive function: a review". International Journal of Andrology, 33(2), pp. 304-316.