This constitutes the third and last episode of our carotenoid saga.  I would have thought, before preparing the topic, to finish in a minor mode… 
But no such thing!  I am in fact fascinated to keep learning such fundamental biological facts thanks to working on these educational 4S emails. 
We all know that beta-carotene represents the vitamin A elective precursor, as one molecule gets oxidized by specific enzyme into 2 vitamin A. 
By the way, I profit by this occasion to remind you the enzymatic transformation occurs in the intestinal lining (enterocytes) thanks to thyroid T3. 
Well, that remains true, but please bear in mind when are sources of beta-carotene available?  They are all summer fruits and vegetables, OK? 
The question then obviously becomes: where do we get our vitamin A from during the winter, when we cannot miss such critical immune player? 
You have your answer: from beta-cryptoxanthin, which is abundant in winter fruits such as persimmons and citrus fruits; satsuma is best source. 
The fact that beta-cryptoxanthin can be converted into vitamin A by the same enzyme as beta-carotene has only been uncovered quite recently. 
However, beta-cryptoxanthin seems to represent a poorer substrate for vitamin A production given reduced efficacy of its enzymatic conversion. 
But that is compensated by much higher beta-cryptoxanthin bio-availability from its foods than what we absorb from foods rich in beta-carotene. 
Take home message: rely on beta-carotene rich foods for the summers, but do not forget about beta-cryptoxanthin rich foods during the winters! 
That is not the end of beta-cryptoxanthin story: it performs wonders on its own.  Once you’ll have read 8 attached articles, you will be impressed. 
I keep attaching our LIST CAROTENOIDS because I have been updating it a lot, recently, especially regarding beta-cryptoxanthin: have a look! 
I wish you a lot of learning and loads of sunshine to wonderfully start July, which is why I unusually send 4S26 on Saturday rather than Sunday. 
2012.04 - A. Role of carotenoid beta-cryptoxanthin in bone homeostasis.pdf
2015.07 - B. Beta-cryptoxanthin as a source of vitamin A.pdf
2016.02 - C. Absorption, metabolism, and functions of beta-cryptoxanthin.pdf
2017.04 - D. Nonalcoholic Fatty Liver Disease and Insulin Resistance - New Insights and Potential New Treatments.pdf
2017.05 - E. Daily oral intake of β-cryptoxanthin ameliorates neuropathic pain.pdf
2017.07 - F. Amelioration of the Development of Osteoarthritis by Daily Intake of Beta-Cryptoxanthin.pdf
2017.09 - G. Beta-Cryptoxanthin ameliorates metabolic risk factors by regulating NF-κB and Nrf2 pathways in insulin resistance induced by high-fat diet in rodents.pdf
2017.10 - H. Beta-Cryptoxanthin exerts greater cardioprotective effects on cardiac ischemia-reperfusion injury than astaxanthin by attenuating mitochondrial dysfunction in mice.pdf


Do you know what is the Migrating Motor Complex?  If not, I am sorry to say that you should know! 
You should because MMC represents a fundamental physiological activity within our digestive tract. 
Of course, you know the other motility pattern leading to digestion, but that’s only half of the story… 
I recommend you read the five attached articles (2 abstracts and 3 full-texts) all highlighted as usual. 
For once, because the topic is of such major importance, I invite you to raise any questions with me. 
What’s for sure: preserving this motility pattern critical for our digestion is incompatible with snacking. 
The best timing for food intake corresponds to two / three meals per day with at least 5-hour interval. 
Overnight fast should last 12 hours at least, ideally expand to 14 hours… or even more if OGG1 SC! 
I wish you an exciting reading despite heat and football.  In fact, I think you can enjoy three together. 
2012.03 - A. The migrating motor complex- control mechanisms and its role in health and disease.pdf
2014.03 - B. Interdigestive migrating motor complex - Its mechanism and clinical importance.pdf
2016.02 - C. Redefining the functional roles of the gastrointestinal migrating motor complex and motilin in small bacterial overgrowth and hunger signaling.pdf
2017.01 - D. Underlying mechanism of the cyclic migrating motor complex in Suncus murinus - a change in gastrointestinal pH is the key regulator.pdf
2017.06 - E. mportance of the enteric nervous system in the control of the migrating motility complex.pdf


Only two articles today to illustrate the topic of the day, i.e. the amazing amino acid “L-theanine". 
But two major reviews, very recently published, that completely cover such fascinating molecule. 
Please read all that is highlighted for you because we should all use that non-protein amino acid. 
It is a prominent central nervous system / CNS active molecule with unique anti-stress properties. 
I frequently use it for myself and for patients to improve sleep especially if waking-up in the night. 
However, its scope appears much larger, boosted by the absence of side-effects and total safety. 
Worth exploring further, I can guarantee… 
I wish you an enjoyable read and Sunday, 
2017.05 - A. L-theanine, unique amino acid of tea and its metabolism, health effects, and safety.pdf
2018.03 - B. L-Theanine - An astounding sui generis integrant in tea.pdf

4S29 - GABA

Insomnia represents a massive issue for many patients and all traditional chemical solutions bring concerning side effects. 

Together with melatonin, 5-HTP, and different herbs, Gamma Aminobutyric Acid (GABA) offers an interesting alternative. 
I am very pleased to announce you that the Journal of Clinical Neurology has just published a GABA study, in July 2018. 
I attach the study as highlighted full-text to save you time reading plus 4 earlier studies that introduce and expand the topic. 
You will find out that giving GABA to enhance sleep shows both effective and safe, with only minor, unfrequent side effects. 
My view is that such publication should comfort us in using GABA as a food supplement well indicated to address insomnia. 
I do my best to keep you updated with latest scientific findings in order to better treat our patients! 
If you have any practical question about this topic, I would be very pleased to answer your emails. 
I wish you a nice summer weekend and I hope you don’t blame me for suggesting some learning?
2002.05 - A. GABA mechanisms and sleep.pdf
2015.01 - B. The Improvement of Sleep by Oral Intake of GABA and Apocynum venetum Leaf Extract.pdf
2015.10 - C. A study on quality components and sleep-promoting effects of GABA black tea.pdf
2016.09 - D. Sleep-promoting effects of the GABA--5-HTP mixture in vertebrate models.pdf
2018.07 - E. Safety and Efficacy of Gamma-Aminobutyric Acid from Fermented Rice Germ in Patients with Insomnia Symptoms - A Randomized, Double-Blind Trial.pdf


Diindolylmethane, better known as DIM, results from the polymerization of indole-3-carbinol better known as I3C. 
Both substances are famous to prevent breast cancer and in fact they do.  But DIM (maybe also I3C) does more! 
I strongly recommend you reading through these 5 attached articles, or at least all texts I have highlighted for you. 
I am not always going to uncover in my short email presentations what comes in scientific articles I found for you. 
Part of your learning journey comes from becoming familiar with publications, their limitations and contradictions. 
What I can tell you right now is that DIM represents another key phytochemical that we should recommend more. 
Enjoy your reading, enjoy your studious summer, and don’t hesitate raising questions about all considered topics! 
2014.05 - A. Attenuation of Carcinogenesis and the Mechanism Underlying by the Influence of Indole-3-carbinol and Its Metabolite 3,3′-Diindolylmethane - A Therapeutic Marvel.pdf
2016.01 - B. Indole-3-Carbinol and Its Role in Chronic Diseases.pdf
2016.07 - C. Chemopreventive properties of 3,3′-diindolylmethane in breast cancer - Evidence from experimental and human studies.pdf
2017.10 - D. 3,3'-Diindolylmethane suppresses high-fat diet-induced obesity through inhibiting adipogenesis of pre-adipocytes by targeting USP2 activity.pdf
2018.07 - E. 3,3'-Diindolylmethane Enhances Glucose Uptake Through Activation of Insulin Signaling in 3T3-L1 Adipocytes.pdf


I hope that you may test patients for zonulin and, if not yet, that you will consider doing it after having read these 6 articles. 
The first one was published in 2016 by Professor Alessio FASANO who has discovered this human protein (back in 2000). 
This article (in full-text) provides a summary of zonulin fundamentals and its involvement in chronic inflammatory diseases. 
I think that you will appreciate five more recent articles that explore innovative connections between zonulin and diseases. 
I feel the most exciting is the 2018 article showing low zonulin level could be a novel biomarker for exceptional longevity
This is not the first time that I spot scientific evidence associating optimal intestinal function with increased life expectancy. 
Do you understand how much all this research is critically important and that sharing such knowledge with patients is key? 
I wish you an enjoyable weekend and above all some fruitful reading, 
2016.10 - A. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases.pdf
2017.04 - B. Increased intestinal permeability, measured by serum zonulin, is associated with metabolic risk markers in overweight pregnant women.pdf
2017.07 - C. Evaluation of circulating zonulin as a potential marker in the pathogenesis of nonalcoholic fatty liver disease.pdf
2017.09 - D. Increased Serum Zonulin Levels as an Intestinal Permeability Marker in Autistic Subjects.pdf
2017.09 - E. Intestinal Permeability Biomarker Zonulin is Elevated in Healthy Aging.pdf
2018.04 - F. Serum Zonulin and Endotoxin Levels in Exceptional Longevity versus Precocious Myocardial Infarction.pdf


We are now going to study two wonderful herbs benefiting adrenal glands among other things, Ashwagandha (‘4S32’ today) and Rhodiola (‘4S33' next week). 
I am attaching 6 articles about Ashwagandha, 3 full-texts and 3 abstracts - all highlighted to help you cover the information without consuming too much time. 
Withania somnifera is efficient and safe.  Indications go well beyond adrenals: stress, anxiety, thyroid function, male infertility, memory, weight management… 
Plus: “ Ashwagandha is used in traditional Indian medicine (Ayurveda) for general debility, consumption, nervous exhaustion, insomnia, and loss of memory. ” 
The first article considers usefulness of ashwagandha in neurodegenerative diseases, which is also new.  Don’t you think all that information is worth reading? 
2014.06 - A. Effects of Ashwagandha (roots of Withania somnifera) on neurodegenerative diseases.pdf
2014.12 - B. An alternative treatment for anxiety - A systematic review of human trial results reported for the Ayurvedic herb ashwagandha (Withania somnifera).pdf
2017.01 - C. Body Weight Management in Adults Under Chronic Stress Through Treatment With Ashwagandha Root Extract - A Double-Blind, Randomized, Placebo-Controlled Trial.pdf
2017.11 - D. Efficacy and Safety of Ashwagandha (Withania somnifera (L.) Dunal) Root Extract in Improving Memory and Cognitive Functions.pdf
2018.03 - E. Role of Withania somnifera (Ashwagandha) in the management of male infertility.pdf
2018.03 - F. Efficacy and Safety of Ashwagandha Root Extract in Subclinical Hypothyroid Patients - A Double-Blind, Randomized Placebo-Controlled Trial.pdf


Rhodiola rosea has gained a significant reputation to help stressed patients,  but do we have scientific evidence? 
I attach 5 articles showing that we do have such evidence and that prescribing this herb is indeed evidence-based. 
I invite you to read these 5 articles, two full-text and three abstracts, all highlighted to save your time while reading. 
Not only will you obtain confirmations about stress, but you'll find out that Rhodiola achieves much more than that. 
Have a nice reading and enjoy your studious Sunday! 
2015.12 - A. The Effects of Rhodiola rosea L. Extract on Anxiety, Stress, Cognition and Other Mood Symptoms.pdf
2017.02 - B. Rhodiola rosea in Subjects with Prolonged or Chronic Fatigue Symptoms - Results of an Open-Label Clinical Trial.pdf
2018.01 - C. Stress management and the role of Rhodiola rosea - A Review.pdf
2018.05 - D. Antioxidant and hepatoprotective effects of purified Rhodiola rosea polysaccharides.pdf
2018.07 - E. Antioxidant and Antibacterial Activity of Roseroot (Rhodiola rosea L.) Dry Extracts.pdf

4S34 - 8-OH-DG

We have covered the other major biological marker for oxidative stress in our email 4S23, i.e.oxidized LDL cholesterol
Today, we study 8-OH-dG that in fact represents in full8-hydroxy-2’-deoxyguanosine, an oxidized nucleotide from DNA. 
If radical-induced damage affects DNA, repair occurs thanks to OGG1 (studied in 4S10) and 8-OH-dG is excreted in urine. 
This urinary biological test should be run as preventive measure, especially for patients who show OGG1 variant genotype. 
I attach five articles, 3 abstracts and 2 full-text (all highlighted) to facilitate your study, that summarize all you need to know! 
I wish you an excellent StudiouS Sunday and a very enjoyable bank holiday (in the UK), 
2004.01 - A. Urinary 8-OHdG - A marker of oxidative stress to DNA and a risk factor for cancer, atherosclerosis and diabetics.pdf
2009.04 - B. 8-hydroxy-2'-deoxyguanosine (8-OHdG) - A critical biomarker of oxidative stress and carcinogenesis.pdf
2015.08 - C. Transcriptional mutagenesis by 8-oxodG in α-synuclein aggregation and the pathogenesis of Parkinson's disease.pdf
2016.04 - D. 8-Hydroxy-2-Deoxyguanosine Levels and Cardiovascular Disease - A Systematic Review and Meta-Analysis of the Literature.pdf
2017.03 - E. 8-Hydroxy-2-deoxyguanosine levels and heart failure - A systematic review and meta-analysis of the literature.pdf


I am providing you today with 4 full-text highlighted articles about an unusual topic entitled “NDT Treatment”. 
Indeed, I am sure that you are not all familiar with the acronym: NDT stands for ‘Natural Desiccated Thyroid’. 
We access and prescribe prescriptive NDT as well as non-prescriptive NDT for a number of thyroid patients. 
Prescriptions consist of American (expensive) ARMOUR THYROID or Canadian (cheaper) ERFA THYROID. 
Non-prescriptive brands are these: Nutri Advanced; Energetica Natura; Biotics Research; Procepts Nutrition. 
You must document yourselves about what exactly these brands contain, as the types of extracts differ a lot. 
I can answer questions, of course.  Besides, you need being aware about the pitfalls met with all these NDT. 
That is main reason for attaching four articles, which besides will enable you to learn historical facts about it. 
I am sure you will be delighted to learn that use of animal thyroid extracts already started 22 centuries ago… 
I wish you an excellent reading and a delightful Sunday to get you prepared for resuming full-speed activities! 
2018.02 - D. LETTER TO THE EDITOR.pdf


Many of us use guggul, i.e. Ayurvedic herb Commiphora mukul, to boost conversion of thyroid prohormones T4 into active hormones T3. 
In fact, guggul delivers more than that, even if numerous activities can finally be linked to improving thyroid function by boosting T3 level. 
I have selected seven articles, two full-text and five abstracts, in order to fast-track you to more understanding of what this herb can bring. 
It is a pretty easy, quick read - for once, will you tell me - because I feel that you are struggling with switching from a lazy summer to now! 
Enjoy the education and your Sunday, 
1999.01 - A. Gugulu (Commiphora mukul) induces triiodothyronine production - Possible involvement of lipid peroxidation.pdf
2005.01 - B. Guggulu (Commiphora mukul) potentially ameliorates hypothyroidism in female mice.pdf
2007.12 - C. Therapeutic Effects of Guggul and Its Constituent Guggulsterone - Cardiovascular Benefit.pdf
2014.09 - D. The appetite regulatory effect of guggulsterones in rats - A repertoire of plasma hormones and neurotransmitters.pdf
2016.01 - E. Guggulsterone and Its Role in Chronic Diseases.pdf
2016.01 - F. Guggulsterone for Chemoprevention of Cancer.pdf
2017.06 - G. Beneficiary effect of Commiphora mukul ethanolic extract against high fructose diet induced abnormalities in carbohydrate and lipid metabolism in wistar rats.pdf


Several among you have seen me often test this enzyme in my patients’ blood. 

It takes a lavender tube, which implies intracellular testing (opposed to serum). 
Myeloperoxidase is expressed in WBC / leucocytes; we look for its deficiency.
This aspect is well summarized in article ‘B’, which uncovers its consequences. 
These show absolutely relevant to intestinal health: impaired microbial killing… 
Articles ‘A’ and ‘C’ tell you more about myeloperoxidase and its basic functions. 
Recently published articles ‘D’ and ‘E’ expand into new findings related to MPx
I hope that you will enjoy a new scientific learning and your Sunday altogether! 
2016.01 - A. Neutrophil-Mediated Regulation of Innate and Adaptive Immunity - The Role of Myeloperoxidase.pdf
2017.12 - B. Myeloperoxidase Deficiency.pdf
2018.02 - C. Myeloperoxidase - Its role for host defense, inflammation, and neutrophil function.pdf
2018.04 - D. Myeloperoxidase as an Active Disease Biomarker - Recent Biochemical and Pathological Perspectives.pdf
2018.05 - E. Myeloperoxidase in the inflamed colon - A novel target for treating inflammatory bowel disease.pdf


Oh yes, this is an overwhelming topic, as you can expect. 
No stress, I just want to bring a few interesting updates… 
I have spotted 5 major reviews published since May 2018. 
I attached all of them here, duly highlighted for quick reading. 
I wish you excellent reading and restful StudiouS Sunday! 
2018.05 - A. Use of Curcumin, a Natural Polyphenol for Targeting Molecular Pathways in Treating Age-Related Neurodegenerative Diseases - FT edited.pdf
2018.05 - B. Curcumin, A Polyphenolic Curcuminoid With Its Protective Effects and Molecular Mechanisms in Diabetes and Diabetic Cardiomyopathy - FT edited.pdf
2018.06 - C. The Role of Curcumin in Prevention and Management of Metastatic Disease - FT edited.pdf
2018.07 - D. Curcumin in Liver Diseases - A Systematic Review of the Cellular Mechanisms of Oxidative Stress and Clinical Perspective - FT edited.pdf
2018.08 - E. Evidence of curcumin and curcumin analogue effects in skin diseases - A narrative review - FT edited.pdf
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