Green Tea and its Extracts for Healthy Brains

The second most popular beverage after water, consumed either hot or cold, is prepared from brewing the leaves of Camellia sinesis: green tea. Different from the equally popular black tea, the fermentation of the leaves is prevented, retaining the eponymous original green color [1].

For a long time, consuming green tea was associated with longevity and increased health, and indeed, green tea was shown to contain the highest concentrations of different polyphenols (flavinoids, catechins, caffeine, theanine, theobromine, theophylline, phenolic acids) as well as antioxidants (epigallocatechin gallate, catechin, epicatechin gallocatechin, gallocatechin gallate, and epicatechin gallate), all of which were shown to be associated with health benefits [2].
A multitude of studies, mainly performed in Asian countries where the plant is cultivated and drinking green tea has a tradition of almost 5000 years [3], reported the health benefits of green tea consumption in various diseases ranging from atherosclerosis, high cholesterol, diabetes, obesity, liver and bowel pathologies to almost all types of cancers [1,4]. In many different types of brain and peripheral nerve tumors, green tea and its extracts were found to inhibit cancer cell growth and render them more vulnerable to chemo- and radiotherapy while simultaneously sparing normal brain cells [5,6].

Source: Will Spark

Prof. Hunstein, a former internist and hematologist, provided a very intriguing self-report on the application of green tea in disease. He suffered from the rare condition lambda light-chain amyloidosis. Whilst the common therapeutic approach was rather ineffective, daily consumption of 1.5 to 2 liters of green tea per day reduced his symptoms substantially [7].
Meta-analyses of studies investigating the effects of daily green tea consumption reveal that there are major variations in the daily intake, concentration, and preparation methods of green tea, and have not found definite proof of clinically relevant benefits [1]. However, more recent studies have relied on chemically pure green tea extracts, more specifically epigallocathechin-3-gallate (EGCG).
This compound was shown to be beneficial for the central nervous system. Since green tea is associated with healthy aging, researchers investigated its effects in diseases of the elderly: Alzheimer's and Parkinson's disease.

Source

In vitro and in vivo models, similar to Prof. Hunsteins amyloidosis report, showed that EGCG decreases A-beta plaque burden by inhibiting peptide aggregation and promoting production of non-cytotoxic peptides through the modulation of secretase activity [8,9]. Additionally, green tea extract acts as an anti-inflammatory compound, scavenging free radicals and promoting hippocampal neurogenesis, all of which are beneficial in Parkinson's disease[10]. The extract does not only prevent cognitive decline by slowing down neurodegenerative processes, but was found to improve cognition even in healthy brains [11]. In small animal as well as human studies, researchers found evidence for the psychological relevance of green tea and its extracts. Reports indicate that green tea reduces stress and even has an antidepressant-like activity. [12,13]
Moreover, there is evidence that EGCG prevents cognitive deficits after stroke, in Huntington's disease and Down syndrome patients [14-16]. Another very promising trial - which was recently performed here at the Charité - investigated the anti-inflammatory actions of EGCG in multiple sclerosis (MS), an autoimmune disease with unknown origin that causes CNS damage by attacking the myelin sheath and causing inflammation and neuronal death [17]. Previous research groups, now present on the Charité campus, had found that EGCG strongly reduces symptoms in the EAE mouse model of MS. The green tea extract is a neuroprotectant and reduced general neuroinflammatory activity [18]. Regarding the now completed clinical trial, project leader Dr. Judith Bellmann-Strobl stated: “We currently evaluate the results of the SuniMS trial. We are about to unblind the data and only then we will know the effects. So far, I can only say that the investigational product was very well tolerated even at relatively high dosages.”

Camellia Sinensis, Source

In conclusion, green tea consumption is very likely beneficial for the body, soul and disease prevention. However, treating individual diseases may require chemically pure compounds found in green tea extracts, which seem to exert few, if any, side effects. It appears that a healthy lifestyle is not only about veggies and exercise; have some green tea to pamper your brain!


[1] bit.ly/1azL2q3
[2] Johnson et al, Maturitas, 2012
[3] http://inventors.about.com/od/tstartinventions/ss/tea.htm
[4] Hursel et al, Am J Clin Nutr, 2013
[5] Das et al, Cancer, 2010
[6] Shervington et al, Mol Biol Rep, 2009
[7] Hunstein, Blood, 2007
[8] Jayasena et al, Ageing Research Reviews, 2013
[9] Lee  et al, J Nutr, 2009
[10] Lee, Neurosignals, 2005
[11] Haque et al, J Nutr, 2006
[12] Zhu et al, Pharmacol Res, 2012
[13]Kimuras et al, Biol Psychol, 2007
[14] Suzuki et al, Med Sci Monit, 2004
[15] Kumar and Kumar, Food Chem Toxicol, 2009
[16] De la Torre, Mol Nutr Food Res, 2013
[17] http://www.gesundheitsforschung-bmbf.de/de/1053.php
[18] Aktas et al, J Immunol, 2004


by Bettina Schmerl, MSc Student Medical Neurosciences
this article originally appeared 2013 in CNS Volume 6, Issue 4, Integrative Medicine

Nature as a Toolbox for Drugs in Neuroscience and Beyond

One of the most difficult steps in developing a drug to treat an illness is finding a biological target for the compound to act on. In many cases, nature has solved this problem for us, and all it takes are a few astute observations from people to figure out how we can make use of our surroundings to improve and maintain our health. Once the effects of a certain plant or animal product on the human body are observed, the exact substance causing these effects must be extracted. Pharmaceutical chemists then synthesize these compounds or compounds closely related to them as a potential drug that undergoes further safety and effectiveness testing.

In areas of the world where malaria is endemic, quinine is one of the most effective treatments for this parasitic infection. Now reserved for the most severe cases of malaria, this drug has been used for centuries in South America and Europe to treat fever and shivering. Quinine is an alkaloid (compounds containing basic nitrogen atoms) derived from the bark of the cinchona tree, and possesses the characteristic bitter taste of this plant. Reserpine, another alkaloid, is a drug used to treat hypertension and psychosis. Although not commonly used nowadays, it remains an option for treating those with high blood pressure who are resistant to other medications. The compound was first isolated from the Indian snakeroot Rauvolfia serpentine. This plant also contains another chemical – yohimbine – which acts on the alpha 2 receptors of adrenaline and is used as a remedy for erectile dysfunction.

The willow tree (genus Salix) has provided humanity with one of the most important drugs we have ever used. The plant contains the active compound salicin, used for centuries to relieve pain and fever by Native Americans as well as the Ancient Egyptians. In fact, salicin was the drug at the centre of the first clinical trial in scientific history, conducted in 1763 [1]. In the late 1800s, it was used for the production of acetylsalicylic acid (Aspirin) - the most widely used drug in history, which single-handedly converted Friedrich Bayer’s company from a small dye manufacturer to a pharmaceutical titan. The cardiac glycoside digoxin is extracted from Digitalis lanata (foxglove). Early attempts at medicinal use of this plant were hindered by its toxicity and fatality in overdose.  It currently has an important role in the treatment of heart failure as well as abnormal rhythmicity of the heart, yet requires stringent monitoring and careful dosage prescription to avoid its harmful effects.

The aptly named plant Atropa belladonna was once used by women in Italy to dilate their pupils and make them look more attractive. It contains a mixture of toxic alkaloids (known to cause hallucinations) that inhibit the action of the autonomic nervous system (the part of the nervous system devoted to controlling the automatic, unconscious functions of the body). Derived from this plant is the widely used anticholinergic drug atropine, which is used in ophthalmology to dilate the pupils, to treat cases of organophosphate (insecticide) poisoning, and to treat those with abnormally low heart rates. Another anticholinergic drug, curare, acts on a distinct set of receptors and was once widely used as a muscle relaxant during anaesthesia. Derived from the Strychnos toxifera plant, this paralyzing poison was historically used by South American tribes to cover the tips of their hunting arrows.

Angiotensin-converting enzyme (ACE) inhibitors were derived in the 1960s from the venom of the Brazilian pit viper, Bothrops jararaca. The venom kills by causing a severe drop in arterial pressure through blockage of the renin angiotensin aldosterone system, an essential physiological mechanism which controls blood pressure. ACE inhibitors such as lisinopril, captopril and enalapril have become first-line agents for high blood pressure, particularly in younger Caucasian patients, and have a good safety profile. It is noteworthy that their selective mechanism of action means that ACE inhibitors may not be effective for everyone in terms of lowering blood pressure. Despite this, the drugs have several other unique benefits including protecting the kidneys in diabetes and improving heart function in patients with heart failure [2].

A more recent drug yielded from nature’s gift basket is exenatide, an anti-diabetic agent licensed for use in 2005. This drug was isolated from lizard (Gila monster) saliva and has been shown to stimulate insulin release from the pancreas [3]. Unlike other anti-diabetic drugs, exenatide has an important feature – it only increases insulin secretion when glucose levels are high and therefore, does not lead to an abnormally low blood glucose (hypoglycaemia). It also has numerous other beneficial effects including promoting weight loss. Similarly, a new agent proposed for the treatment of stroke is also derived from saliva - that of the vampire bat Desmodus rotundus. This drug, called desmoteplase, is still in the testing phases of development (phase III trials), but has already shown great promise [4]. It stays in the body for a longer time than other thrombolytics (drugs which dissolve blood clots), is more selective in its action, and does not lead to neurotoxicity. It is possible that it may represent a breakthrough in the treatment of stroke, which is currently a highly debated and complicated issue.

People have been using natural resources for medicinal purposes for millennia

Nowadays, we are in possession of complex methods to design, test and use medicines. Despite this, it’s not uncommon that a drug crosses our path which reminds us that no matter how technologically advanced we are, our dependence on nature is eternal. People have been using the earth’s natural resources for medicinal purposes for millennia, and continue to do so. However, only a handful of these substances - which include both animal and plant products - have been scientifically deemed safe and effective enough for modern use.


[1] Stone, Philos Trans, 1763
[2] Pahor et al, Diabetes Care, 2000
[3] Gavin, Ethnic Dis, 2007
[4] Schleuning, Pathophysiol Haemos Thromb, 2001


by Ahmed Khalil
this article originally appeared 2013 in CNS Volume 6, Issue 4, Integrative Medicine

Research on Researchers: Dr. Michael Teut

Dr. Michael Teut does clinical research about the effects of traditional, alternative or complementary therapies and works as a physician at the Institute of Social Medicine, Epidemiology and Health Economics, Charité Universitätsmedizin Berlin.




MZ: What is your academic background?
MT: I was trained as a physician, mainly in Internal Medicine, Geriatrics, Family Medicine, Hypnotherapy and Complementary and Alternative Medicine. Since 2007, I have been working as researcher and physician at the Institute of Social Medicine, Epidemiology and Health Economics, Charité Universitätsmedizin Berlin.

You studied in the Netherlands and in India. What did you experience there?
Both countries have completely different cultures. In 1994, I spent a few months of clinical training in a homeopathic hospital and college in Mumbai. India’s medical system is split into three parts: conventional medicine, ayurveda, and homeopathy. Approximately 250,000 Indian physicians work as homeopaths and are running hospitals and clinics. I personally wanted to study this phenomenon more closely and subjectively had the impression that, in many cases, homeopathy produced good results, but in others, conventional medicine was clearly superior. This experience helped to support my decision to pursue Integrative Medicine, which combines the best therapeutic strategies from different systems to optimize health care for individual patients with individual needs. In the Netherlands, I participated in a four-month surgical internship at the Leiden University Medical Center, which was very good training. Practical bedside teaching was of utmost importance and I participated in many operations and worked frequently in the emergency unit. Teamwork was clearly very important, and was a strength of the Dutch colleagues.

What do you do in your current position?
Together with my colleagues, I was able to set up the Charité Outpatient Department for Integrative Medicine at Berlin Mitte (Charité Hochschulambulanz für Naturheilkunde), which provides outpatient care and conducts clinical trials. I am also teaching medical students in Social Medicine, Prevention, Health Economics and Complementary and Alternative Medicine. At the moment, we are running clinical trials on the effects of mindful walking and cupping in chronic low back pain and „Kneipp“ therapies in elderly patients in nursing homes.

What are your main topics of interest in science?
I am mainly interested in clinical research about the effects of traditional, alternative or complementary therapies. If you enter this field, placebo discussions will automatically arise. In the last years, I became more and more interested in ’self healing‘. In clinical research, the term ’placebo‘ is frequently used. But placebo is a ’black box‘, the meaning depends on the context in which the term is used. In my understanding, one important aspect of ’placebo‘ is self healing and conditions which support self healing. Already the school of Hippocrates in ancient Greece advised life style changes to increase self healing, to improve health, and support healthy aging. Much of the ancient advice remains true today. Although we know about the benefits of lifestyle change, modern medicine is mainly focused on technical solutions. Therefore, I consider trials that investigate the effects of simple and low-tech lifestyle change interventions to be of high importance. Good examples are our trials about the effects of mindful walking exercises on psychological distressed subjects or patients with chronic back pain.

Scientific research should be understood as a tool to help patients and improve medicine.

What do you think is the main advantage of integrative medicine compared to conventional medicine?
Over the last years, I realized that integrating traditional therapies in conventional medicine enables physicians to use a wider range of metaphors and concepts to help patients to create meaning about their complaints and disease. This can help the patient to reframe his situation, reduce distress, and also activate resources for self healing. Physicians integrating traditional therapies usually spend more time with their patients. Time is a crucial resource to medical quality: to understand patients, build up a good patient-physician relationship, also to avoid errors. In addition, many traditional therapies have low side effects and can be tried before, after or in combination with conventional treatments.

How will medicine look like in 20 years from now?
Medical progress is strongly driven by new technologies and industry. Introducing new technologies confronts us with great opportunities but also risks. I hope that we will be able to master this challenge and our patients may benefit from technical advances. In the United States, Integrative Medicine has become a very strong movement. Nearly all academic centers are now running departments for Integrative Medicine. The US government strongly supports scientific research in this field with more than 100 million dollars per year. I personally understand this movement as a counterbalance to the technologically driven medical progress. I hope that creating evidence for traditional therapies may lead to an integration of useful strategies in conventional medicine in the long run.

What impressed or astonished you most during your career?
The tendency of many physicians and journalists to generally classify complementary and alternative medicines as ’placebo‘ and conventional medicine as ’effective‘. Both sides are part of our medicine culture. Placebo responses occur in both systems and play essential roles in both. Conventional medical practice, as practiced in real life, is in many cases not evidence-based. We should generally be more open minded, curious, but also critical towards all therapeutic strategies.

Thank you very much, Dr. Teut, for this intriguing insight into your work and life. 

This interview was conducted by Marietta Zille and originally published 2013 in
CNS Volume 6, Issue 4, Integrative Medicine

DeepMind - Will Transparency Make Us Healthier?

You might have heard of DeepMind last year, when they invented a program that could beat human players in the game Go. The British artificial intelligence company, now owned by Google, has been pushing the boundaries of algorithmic learning research for some time now. I was interested to learn that currently their main field of application is healthcare. An entire division of the company is working on a range of challenges with medical data, from interpreting medical images to integrating patient data, all under the banner of DeepMind Health [1].

This work has been taking place in collaboration with a number of UK NHS foundation trusts. For example, a project aimed at detecting and predicting ocular degeneration from digital eye scans is the outcome of a collaboration with Moorfields Eye Hospital London, who have granted access to their database of anonymized digital images of the eye. Similarly, patient CT and MRI scans from University College London Hospital are being used in a machine learning approach to improve treatment planning for head and neck cancers.

How Big Data Helps Medical Professionals
Their largest project has been a collaboration with the Royal Free London NHS foundation trust and Imperial College Healthcare NHS trust in developing a mobile app to provide real-time patient information to nurses and clinicians. Called Streams, this app intends to speed up communication and decision making in hospital environments by replacing a number of older solutions relying on papers, fax, or pagers. The intention is to consolidate a patient’s medical results within a single interface where data-driven alerts can be sent out as soon as there is any indication of a problem, and actions can be decided upon by relevant health workers. The current focus is on a specific disorder, acute kidney injury, where such an approach is presumed to be particularly promising, but obviously the vision extends far more broadly.

Image via pixabay

From this technology, it is not difficult to imagine a future where data from multiple continuous bio-monitoring sources could be integrated so that patients, or any individuals, could be diagnosed and monitored in real-time. Glimpses of this path can already be seen with existing technology like continuous glucose monitoring devices, which provide continuous real-time blood-glucose measurements to diabetics, the data from which can then be accessed (and sometimes shared) via mobile apps [2]. Perhaps even more seemingly mundane biological data could be insightful from a medical perspective - think what information a Fitbit might reveal if state-of-the-art machine learning were applied to its data. Integrating all of these varied sources of information together to generate a comprehensive and detailed medical picture of an individual is surely something DeepMind Health have thought about as well.

DEEPMIND HAVE TAKEN A TRANSPARENCY APPROACH

This whole idea rests upon the ability for a private company to access potentially sensitive patient medical data, and DeepMind were doing just this, often without patient consent. Predictably, this drew some criticism. DeepMind responded earlier this year in an interesting way. Rather than attempting to seek patient consent, they instead took an approach of transparency by announcing their development of a data-logging process - the verifiable data audit.

Transparency vs. Data Privacy
The idea is that a record of all interactions with patient data will be generated and saved, with a log of who was accessing an element of data, when, and for what reason. This record will be automatically updated and stored in a semi-decentralized manner that has been likened to blockchain, with records in a distributed network of healthcare institutions such as hospitals. The data is structured so that any time it is accessed or changed this will be immediately recorded. As such, guidelines can be put in place to ensure that the data isn’t used in unauthorized ways. It also means that all access of data will be traceable forever in a way that should be tamper-proof.
At the epicenter of all this technological innovation is data - as the 21st century is starting to teach us, data is powerful and data is valuable. So where there is a question of data, there is always a question of privacy trailing close behind. If we can imagine these technologies, we must also be able to imagine a future where our most intimate biological details are shared widely and accessible to many. The price of a detailed understanding of our own body is perhaps our privacy in that matter.
In this discussion, DeepMind are not strictly advocating privacy - rather, they are advocating transparency. Yes, your data will be accessed by many people, but with a strict record of who and for what purpose, which will ideally necessitate adherence to data sharing guidelines. Before patients themselves have access to their own records, this will likely still sit uncomfortably for many people. Until then, the success or failure of initiatives like DeepMind Health will determine how willing we are as a society to invest our data in our health, and to whom.


[1] http://bit.ly/2nfaDQ2
[2] http://bit.ly/1QM9PKF

by James Kerr, PhD Student AG Sterzer
this article originally appeared June 2017 in CNS Volume 10, Issue 2, Digital Health and Big Data  
 

Conference Report: World Health Summit

Hold once a year, the World Health Summit (WHS) has grown into the world’s most prominent forum for addressing global health issues. It takes place in Berlin and brings together key leaders from academia, politics, civil society, and the private sector to address the most pressing health-related challenges on the planet. Until July 31, 2017 students can register for 69 EUR. Some of our students attended the WHS last year.

By chance I was even wearing the WHS colours.

During the eighth World Health Summit (WHS) 2016, a lot of big and ambitious topics were discussed: medical care for refugees, access to medicine, epidemics such as Ebola or Zika, non-communicable diseases such as stroke, antimicrobial resistance (which constitutes one of today's major health challenges), translational research, technological innovations, data management and empowerment of women.

The WHS brought together about 1800 researchers, physicians, government officials, representatives from industry, non-governmental organizations, and healthcare systems from more than 90 countries to discuss the most pressing issues facing every facet of healthcare and medicine in the upcoming decade and beyond. Prominent participants were Herrmann Gröhe, the German minister of health, Emanuelle Charpentier from the Max Plank Institute for Infectious Diseases and Pascale Ehrenfreund from the German Aerospace Center ... just to do some name dropping.

NOT YOUR AVERAGE 

SCIENTIFIC CONFERENCE

Rather than a series of snooze-inducing presentations, the three days were full of open dialogues and discussion rounds in small rooms with a handful of appointed speakers who gave short presentations, followed by group discussions with plenty of opportunities to ask questions. The atmosphere was very inspiring and everyone from high-level policy makers to students held discussions together as equals.

One highlight of the conference was the startup track pitch competition. This included amazing contributions such as Midge Medical, who invented a new blood testing device for malaria, or the startup Glasschair, who developed a wheelchair that can be navigated by eye movements, or COLDPLASMATECH, a startup that produces an amazing new solution to help wounds heal faster.

Attending this conference was a great opportunity to break beyond my comfort zone, meet interesting people from the health sector and of course do some networking (I recommend printing business cards if you want to go). But above all, it was a great conference to get updated on global health issues, and it made me want to focus even more on the translational aspect of science.

The conference ended with a call to action in five key central areas of global health: 

1) Empowerment of Women and Girls

2) Right to Health of Refugees and Migrants, 

3) Resilience and Global Health Security, 

4) Sustainable solutions against antimicrobial resistance, 

5) Investment in Research, Development and Health Innovation. 

It's all tall order, but nonetheless a good start!

by Claudia Willmes, PhD Alumni AG Eickholt/AG Schmitz

this article originally appeared  2016 in CNS Volume 9, Issue 4, From Cradle to Grave in the Brain