Supplements: Hype, or Helpful?

 

Supplements: Hype, or Helpful?

 Annalies Corse BMedSc, BHSc

Written for and originally published by the MINDD Foundation: www.midd.org

In an ideal world, people all over the world would be able to obtain the nutrition they require from diet alone. So many factors (no matter what country you live in) make this very unrealistic in the modern age. Some people simply don’t have access to food, and food supplements are essential to their health. For those of us in wealthier countries, there are several environmental, genetic and clinical reasons why seeking supplement prescription may be necessary for your health. Many supplements are purely born of health fads and hype, but some are essential. In certain cases, supplements are life saving, and provide us with the kind of health that we cannot achieve through diet alone. Consider some of the following situations, as all are legitimate reasons as to why supplements are necessary for many modern humans:

  • The quality of our soils is not what it used to be. Foods grown in soil depleted of nutrients, trace minerals and healthy soil microbes has a direct impact on plant, animal and human health.
  • Our world is more polluted. Soil, water, air, the workplace and households expose us to heavy metals and other pollutants. A healthy diet will undoubtedly protect us from most of the harm these can cause, but specific supplements are essential to support our endogenous detoxification systems.
  • Our own health history plays a huge part in our need for nutrient supplementation. Damage to the digestive system through leaky gut antibiotic exposure, refined carbohydrate diets, caesarean section birth, substance and medication use all increase our requirements for nutrients that may not be addressed through diet alone.

Do you know all the important factors you must consider before you embark on taking a food, vitamin or mineral supplement? Have you asked yourself these essential questions?

  • Have I been advised to take this supplement on the advice of a qualified health professional?
  • Will this supplement interact with my current medications?
  • Will this supplement be ok, based on the other supplements I currently take?
  • Has this supplement been formulated based on good quality control practices?
  • Is there clinical and scientific evidence for this supplement?
  • What else is in my supplement, besides the active constituents and ingredients?
  • Could I achieve my health goals in another way?
  • Is the formulation and dosage correct for my condition, life stage and age?

Obviously, all of this is a lot to consider, especially if you are not a health professional. No one should be expected to know the answers to these questions regarding supplements, that is why it’s essential not to self prescribe and to only commence supplementation after consultation with a Naturopath, Nutritionist, Dietician or a Doctor or Pharmacist with specific education in nutrition. There is abundant hype when it comes to nutritional supplements; the amount of celebrity endorsements for over the counter (OTC) supplements attests to this. Let’s take a look at which supplements are hype, which are helpful, and exactly why this is the case.

 OTC supplements from retail environments

Some are well formulated, but some are not. What is in their favour?

  • Most are affordable
  • You can purchase quickly on the spot

What is not in their favour?

  • Often sold without any consultation with a health professional
  • Many are cheap due to poor quality ingredients
  • Formulations may not have clinically relevant levels of the vitamin or mineral required

There are some excellent OTC supplement products, but always seek assistance from a professional who has studied them. Many practitioners recommend retail ranges, but they do so based on objective clinical opinions. If a store or clinic only supplies 1 or 2 brands, it’s a sign to be wary of. Good, objective clinical practice means prescription based on formulations, not brands. Companies not associated with health at all manufacture some OTC supplements for commercial reasons. It is definitely an area where you will be exposed to more hype that help. Ask a professional for their advice first.

Practitioner only supplements

Regarding supplements, these are the gold standard. These are formulations based on excellent quality control practices, years of education, clinical experience and thorough case taking. Depending on the situation, they can be prescribed in a pharmacy or retail setting, but only by a Naturopath, Nutritionist, Doctor or Pharmacist with extra training. In an ideal world, they should only be prescribed after an appointment with a health professional. A word of advice must be given to those with extensive or chronic health issues; purchasing a supplement after a quick chat with a practitioner will probably not be enough time to ascertain exactly what will be the best protocol for your health, going forward. In virtually every case (acute or chronic) it is much better to sit down with a practitioner, so they can thoroughly go through your medical history, diet and medications history.

So, are practitioner only supplements hype? Mostly, not! They are formulations often put together based on studies, human biochemistry and nutraceuticals research. There are definitely times where you will not be required to take supplements long term, just a short course may be needed. If you have a great diet, you will likely not need to supplement any nutrient long term.

A special word of advice must be given to supplements containing herbal medicines. Herbal medicine is a highly specialised area of complementary medicine, and it takes years of education to be thoroughly effective and safe with prescription. They should never be prescribed by those with no education or expertise in herbal medicine, so avoid purchasing from any person or professional who does not have a specific qualification in herbal medicine.

Supplements purchased online

When purchasing a supplement online, there are two significant issues people face. Firstly, many will not be part of a therapeutic regulatory process, where only sound and good quality medicines and supplements make the grade and are deemed safe for the public. Some contain dubious ingredients, and there is a risk of purchasing something with negligible therapeutic action. The actual doses of vitamins and minerals may be too low or poorly formulated to provide any benefit.

You may find that some well-known retail or even practitioner only brands are available online. Again, if you access these without advice from a health professional, there is high probability they won’t be perfectly suited to you. This is where many people experience disappointing results from supplements.

Tip: Consider how much money you spend every few months on your hair, on coffees or at cafes and restaurants. A consultation with a complementary health professional once or twice a year is a huge investment in your health. You will avoid the supplements that are just hype, and you will have access to a professional who will spend ample time getting to the initiating factors of your health issues.

Food based supplements

Food based supplements cover the spectrum of powders, liquids, gels, drinks, shakes and snacks. The array of food supplements seems to multiply every month, but there are ways to be savvy and avoid hype. Ask yourself these questions before potentially parting cash on something that sounds fantastic, but may not do much for you:

  • Could I just spend money on real food? Will a powdered fruit and vegetable product be any better than fresh produce?

Fresh is always best, and so much more delicious. Many vitamins are exceedingly delicate, and there is no guarantee they have remained active or viable in a food supplement. Consider how processed the food supplement is first, before you purchase.

  • I eat really well, a wholefood diet with ample fruit and veg, good quality fats and protein. But I’m still not experiencing the health I desire, and this food supplement is apparently great for my problem.

 There are other ways to achieve good health without supplementation, and other areas apart from diet that contribute to poor health. Before reaching for the latest super food powder, be honest with yourself or with a practitioner about your sleep, stress levels, physical activity levels and lifestyle practices. Supplements may rightly still be required, but you might need less than you think.

A good health professional will always prescribe supplements when the benefit they have for your personal clinical condition or health matter outweighs any risk. Your health provider should be able to state exactly the reasons for taking a supplement, and they will follow up with you to measure your outcome. It is often not necessary for most people to be on long courses of supplementation; some people with specific health conditions will be, but they are monitored very regularly to assess if the supplementation needs to change. In conclusion, supplementation is only helpful when professionally prescribed. Any thing else runs a risk of exposing us to a fad. Health fads come and go, as do some supplements. Good health practitioners are acutely aware of this. Always source their expertise before potentially wasting your money. Modern living definitely makes us somewhat vulnerable to nutrient depletion, so ensure you are taking the right supplements at the right dose to protect you and your family’s health In to the future.

 

References

 

  1. Brevik, E. C. & Burgess, L. C. (2014) The Influence of Soils on Human Health. Nature Education Knowledge 5(12): 1

 

  1. Harvard T. H. Chan School of Public Health. (2016). The Nutrition Source. Available at: http://www.hsph.harvard.edu/nutritionsource/

 

  1. Herbert, V. (1973). The Five Possible Causes of Nutrient Deficiency: illustrated by deficiencies of Vitamin B12 and folic acid. The American Journal of Clinical Nutrition. 26 (1): 77-86.

 

  1. Neu, J. (2011). Cesarean versus Vaginal Delivery: Long term infant outcomes and the Hygiene Hypothesis. Clinical Perinatology. 38 (2): 321-331.

Image credit: Dieta Ortomolecular

Porphyrins vs Pyrrol Testing: Is there a Difference?

 

Porphyrin versus Pyrrole Testing. Is there a Difference?

 Annalies Corse BMedSc, BHSc

Written for and originally published by the MINDD Foundation. www.mindd.org

Pyrroluria is a condition known by many different names including Pyrrole Disorder, Mauve Factor and the older, unused names Kryptopyrroluria and Malvaria. It is described as being a metabolic condition, which essentially means it is a condition of altered body biochemistry. Pyrroluria disrupts a very specific aspect of our human biochemistry involving haem, an important chemical component of haemoglobin (the major oxygen carrying protein found in our red blood cells). It is also described as a genetic condition, with mounting clinical evidence the condition can be passed on from one generation to the next. Whilst a gene for Pyrroluria is yet to be found, the condition runs strongly through families. Experts in this field estimate that if a parent has Pyrroluria, there is a 50:50 chance it will be passed on to a child. This rises to a 75% chance of inheriting the disorder if both parents have it.

The name Pyrroluria is a technical term that essentially means excess levels of pyrroles in the urine. The condition was initially identified in the 1950’s and was known as ‘Malvaria’. Pioneers in the field of Pyrroluria research include Dr Abram Hoffer, Dr Humphrey Osmond and Dr Carl Pfeiffer. The condition is recognized by Doctors of Orthomolecular Medicine, Orthomolecular Psychiatry and Integrative Medicine, but remains largely unknown in Orthodox Medicine. Patients with Pyrroluria will also have problems associated with deficiencies of vitamin B6 and zinc. This is because the chemical by-product associated with Pyrroluria binds to both B6 and zinc, reducing the levels of the nutrients available for important biochemical pathways. Signs and symptoms of pyrroluria are essentially those of B6 and zinc deficiency and can include:

 

  • Anxiety
  • Mood swings, outbursts of temper, depression
  • Sensitivity to loud noises and bright lights
  • Morning nausea and poor morning appetite
  • Histrionic (dramatic)

 

A second, less subtle condition related to Pyrroluria is known as Porphyria disorder. This is a group of disorders with abnormalities involving the synthesis of haeme. These are again genetic in origin, and mainly affect the skin (cutaneous porphyria’s) and the nervous system (cutaneous porphyria’s). The prevalence around the world varies dramatically, with estimates ranging from 1 in 500 to 1 in 50, 000 worldwide having a genetic trait that causes some form of porphyria. The condition is rare and has extremely varied presentations, ranging from severe anaemia’s, severe cutaneous blistering and serious digestive disturbances with seizures. Acute attacks often present during times of physiological stress.

 

For parents and carers (and indeed, practitioners), finding useful information regarding Pyrolluria can be a very lengthy and frustrating experience. Much of the information available online is from commercial sources or may not be written by scientifically qualified health professionals. The good quality, scientifically based information is out there, but it can be difficult to understand the scientific terminology used.

 

To add further confusion to this condition, there are currently two methods of laboratory assessment for Pyrrole Disorder; testing the urine for hydroxyhemopyrrolin-2-one (HPL), the key structural component of Mauve Factor. This is the test that has been honed and developed with specificity for Pyrolluria testing in mind. Additionally, porphyrin testing is occasionally suggested as another laboratory option when investigations for Pyrrole Disorder are warranted.

 

Porphyrin Testing

 

We all make porphyrins; they are essential structures required for the synthesis of haemoglobin and the cytochromes of energy production and liver detoxification pathways (to name a few). Naturally, we also must excrete porphyrins to prevent their build up. In orthodox medicine, a group of very rare diseases known as the Porphyrias involves the incorrect breakdown and excretion of haemoglobin. They are present is very large amounts in those with Porphyria and can be detected in blood, urine and fecal samples. The porphyrias are readily diagnosed by laboratory testing, especially at or near the time of symptoms. However, the number of tests available is very large, and the results among laboratories are not always reliable. For these reasons, it is important to locate a laboratory skilled in performing tests for Porphyria and a physician skilled in interpreting the test results. At present, some laboratories offer porphyrin testing as an alternative to pyrrole testing. Both the porphyrin structures and pyrrole structures are breakdown products of haemoglobin; porphyrins can simply be broken down further into pyrroles. Arguments in favor of porphyrin testing are that the structures tested are relatively stable, though it is not specific for Pyrrole Disorder. With pyrrole testing, if followed correctly it is highly specific for Pyrrole Disorder, but the substance tested is very fragile and prone to breakdown if not handled correctly by patients and lab staff.

Pyrrole Testing

Reliable pathology testing for Pyrroluria is available both in Australia and overseas. The testing method is based on urine analysis and determines if the patients urine a) tests positive for the presence of excessive amounts pyrroles and b) determines (quantifies) the actual level present in the urine. Pathology testing is essential for both adults and children with Pyrroluria, and correct diagnosis is essential to rule out other possible conditions that can often present in the same way.

 

Laboratory research into Pyrroluria has been occurring since the early 1970’s, with pathology testing becoming more sensitive and specific in that time. Original research thought that Mauve Factor was a chemical compound known as kryptopyrrole. However, as technology has improved it has been identified that a related compound, hydroxyhemopyrrolin-2-one (HPL) is the key structural component of Mauve Factor. Laboratories will usually be looking to detect HPL in their testing methods. Pyrroles are excreted from the body in urine, so this test is a reliable marker for detection of this metabolic condition.

 

This urine test involves the patient providing a small sample of urine, usually between 25ml to 50ml (the standard amount you would provide for most routine pathology testing). The normal amount of HPL in urine is less than 10mcg (micrograms) per dl (decilitre), often written as < 10mcg/dl on testing reports. To put this in context; there are 1000 micrograms in a milligram, and 10 decilitres in a litter, so what is being detected is a very tiny amount, yet significant enough to confirm the condition is present.

 

Urine must be collected in two vials, one of which contains ascorbic acid (vitamin C). Both vials must be wrapped in foil and frozen immediately for transportation to the lab. The reason for foil wrapping and freezing is that pyrroles break down quickly and are highly unstable when exposed to light. Pyrroles are also very sensitive to oxidation by air, which is another reason why samples need to be handled with care and that all instructions regarding the specimen are followed correctly.

 

Once at the laboratory, the urine sample is tested via a process known as spectrophotometry. Spectrophotometry is used extensively in pathology and research laboratories all over the world for many types of tests besides Pyrroluria testing. It is a highly evidence based and reliable scientific technique when the detection of very small amounts of a substance is required. It is a relatively rapid method, where a machine known as a spectrophotometer measures the amount of light absorbed by the patients urine sample. Pyrroles absorb and reflect light at specific wavelengths, so their presence in urine can be detected by the spectrophotometer.

 

Urine testing for Pyrroluria is quantitative, meaning that the quantity of pyrroles present can be measured as a numerical value (the intensity of the colour is recorded and the calculation of the result is carried out). So, rather than just receiving a result that states a patient is ‘positive’ or ‘negative’ for Mauve Factor, the test provides a value result. Quantitative pathology tests are very useful in this instance, as you can observe the level of pyrroles in the urine coming down with treatment, even though the level might still remain high. Practitioners and patients can use the test to observe the response to treatment, or if the treatment needs to be modified in some way. Seeing the pyrrole result decrease is very useful for patient compliance, even for children.

 

Test results that will require follow-up and possible referral and treatment include:

 

Borderline Pyrroluria: HPL between 10-20 mcg/dl

Positive Pyrroluria: HPL > 20 mcg/dl

 

In Australia, it is important to note if a laboratory is accredited with NATA for pathology testing. NATA is Australia’s authority responsible for the accreditation of laboratories, ensuring high standards of technical competence and best practice. If a lab is not accredited with NATA, you can discuss this with your practitioner, as they will have knowledge of the laboratories methods and quality control practices.

 

In addition to the urine test for Pyrroluria or porphyrins, a practitioner may suggest other tests at your initial appointment. Depending on the individual case and the symptoms present, it may also be necessary to have other functional or routing pathology testing organized, such as testing for methylation disorders or testing digestive health and bowel microbes. Testing can be expensive and it’s impossible to interpret the results and self-prescribe without clinical expertise, so ensure you have organized an appointment with an Integrative doctor first. It may be the case that only very few tests need to be organized when you consult with a health professional with experience in testing for and treating Pyrroluria.

Individuals with Pyrrole disorder require supplementation with B6, zinc and possibly evening primrose oil. This nutrient regime is essential to replace the nutrients that are rendered inactive by the build-up of HPL in the body. What is interesting is that each individual will require their own unique dose to achieve the best results, and the nutrients can be titrated (i.e., adjusted quickly) to deal with changing signs and symptoms, or increased during times of physiological stress to prevent attacks. This is most definitely a health condition that requires nutrient prescription from an integrative health practitioner.

 

Detecting Pyrroluria in adults is always a little trickier in clinical practice. Adults need to be willing to get tested, and willing to do the treatment. This is another reason why detecting the condition as early as possible in childhood is always the best option.

 

 

 

 

References

 

  1. Badawy A, Morgan, C. (1980). Tryptophan pyrrolase in haem regulation. The relationship between the depletion of rat liver tryptophan pyrrolase haem and the enhancement of 5-aminolaevulinate synthase activity by 2-allyl-2- Biochemical Journal. 186(3): 763-72

 

  1. Harris K. Walsh Research Institute. BioBalance Conference. Pyrroluria, Gold Coast Conference; seminar given 2013 April 17.

 

  1. McGinnis W, Audhya T, Walsh W, Jackson J, McLaren-Howard J, Lewis A, et al. (2008). Discerning the Mauve Factor, Part 1. Alternative Therapies in Health and Medicine. 14 (2): 40-50

 

  1. McGinnis W, Audhya T, Walsh W, Jackson J, McLaren-Howard J, Lewis A, et al. (2008). Discerning the Mauve Factor, Part 2. Alternative Therapies in Health and Medicine. 14 (3): 56-62

 

 

 

 

The Intricacies of Immunity.

The Intricacies of Immunity: Why Your Immune System is Vital for Health at Every Level.

Annalies Corse BMedSc, BHSc

Anyone who has studied the immune system in depth has a deep appreciation of the intricacies, complexities and vast functions of this defensive network of protective structures and processes. It is arguably one of the most difficult systems of human anatomy and physiology to study; the seemingly limitless cell populations, biochemical reaction cascades and molecular categorisations of the immune system all require great attention to detail to understand them well. Ultimately, the immune system serves to protect us from both infectious and certain non-infectious diseases. However, the role of our immune system is targeted at significantly more human health issues than attacking pathogenic microorganisms. This system serves us at almost every level of our health; many other physiological systems rely on the strength of our immune system in order to operate properly. This is why Immunological disorders are central to the core principles of the MINDD Foundation.

Anatomy of the Human Immune System

A network of cells, tissues, nodes, nodules, ducts and vessels scattered throughout your body, the immune system responds to everything from invading microorganisms through to foreign tissues and cells (including cancerous cells). The immune system performs much of its physiological functions via lymphatic tissue. The lymphatic system is sometimes described separately to the immune system, however both work together for immune defence.

Spanning all regions of your body, the lymphatic network of vessels, capillaries, tissue and nodes primarily transports lymphatic fluid from peripheral organs and tissues before it is returned to general blood circulation. Lymphatic tissue and nodes are responsible for screening this fluid for pathogens, abnormal cells and other cellular complexes deemed to be ‘waste’ by the body. This ensures lymphatic fluid entering the general circulation is essentially cleaned of unwanted and unnecessary immune debris.

Lymphatic tissue is arguably some of the busiest tissue in the body. Lymphatic tissue located within specific skeletal tissue is haematopoietic (blood cell producing). Your five tonsils (2 paired, 1 singular) are perfectly located for their role in oropharyngeal and nasopharyngeal defence. Masses of lymphatic tissue located in the illeal region of the small intestine known as Peyer’s Patches monitor digestive content for possible pathogens. The upper left abdominal quadrant is the location of your spleen, an organ involved in screening blood for infections, abnormal cells and immune complexes. Immediately anterior to the heart is the Thymus gland. Very active in childhood and adolescence, the Thymus is involved in contributing to the ‘memory’ aspect of immunity, knowing which infections and immunisations one has been exposed to.

Adaptive and Innate Immunity

While possibly not as physiologically complex as adaptive immunity, innate immunity is critical for the protection of other sensitive, specialised and vital organs. Innate immunity involves secretions such as mucous, tears, acids, saliva, sebum and cerumen (wax). Mucous is produced not only in the respiratory system, but also in the gastrointestinal system and reproductive system for this reason. Fever and inflammation are both examples of innate immunity, and both signify an attempt by the body to speed up the immune system, slow the reproduction of a pathogen, prevent the spread of localised infection and deliver cells of the immune system to an area of infection or damage.

Collectively, innate immune responses are not selective; the hallmark of these responses is their ability to regard to all pathogens, physical tissue destruction and atypical cells as a problem. Without healthy innate immune mechanisms, your general blood circulation can be accessed by invading microbes, meaning infections spread easily. Nutrition, herbal medicine, acupuncture, manual therapies and lifestyle medicine is essential to buttress these defences to work in your favour.

Adaptive immunity involves responses that are highly specialised and targeted toward a specific pathogen or antigen (foreign substance). Adaptive immune mechanisms are those involved in providing the body with lasting, sometimes life-long protection from certain infections. The ability to distinguish foreign tissue from ‘self’ tissue is a hallmark of the adaptive immune system. When one’s immune system responds to a normal healthy tissue structure as ‘foreign’ and reacts with destruction, the ensuing disorders are known as autoimmune diseases.

Cells of the Immune System

As stated earlier, the cells of your immune system are produced in the red bone marrow. After a series of maturation events occurring in the Thymus, general blood circulation or other lymphatic tissues, the cells of your immune system comprise the following:

  • Neutrophils
  • Lymphocytes
  • Monocytes
  • Eosinophil’s
  • Basophils

Each category has multiple cellular subtypes; some so specific and diverse there are hundreds in each category. While many are involved in the innate immune defences of inflammation and fever, others are so specialised they only respond to a specific species of microbe or antigen (foreign protein).

Immunodeficiency

Immunodeficiency is a significant health issue; the incredibly vast structures, cells and pathways of immune responses mean that immune compromise involves any and many parts of the immune system. Immunodeficiency disorders include the following:

  • Inherited: these are genetic disorders running in families. Examples include diseases affecting the body’s ability to synthesise antibodies during infections. These disorders are rare; some are lethal due to the inability to control serious infection.
  • Acquired: this occurs due to other pathological events or malnutrition. HIV infection, cancer, splenectomy and diabetes are all associated with diminished immune strength. Nutrition and lifestyle medicine warrants special attention, as both contribute heavily to both the strength and adaptiveness of your immune responses in all phases of life, from the neonatal period to elder age.

Complementary and Integrative Health Perspective

For those of us who do not suffer a chronic illness with severe consequences for immunity, this system does a wonderful job in keeping us healthy. For some people, autoimmune diseases threaten quality of life and diminish our wellbeing. Allergies and recurrent or low-grade infections seem to now plague modern society. Those with generally robust health who invest time and effort into their health may regard an infection as a ‘failure’ of their immune system.

Complementary and Integrative medical practices can support the functions of the immune system at many various levels. There is no one single practice, food, supplement or lifestyle intervention that will suddenly ‘boost’ the immune system. Immune responses are so intricate, multi-layered and involve so many different cells, reactions and tissues that a long term approach is required to support immune health, usually from many different clinical angles including nutrition, exercise, premature aging, toxin exposure, psychological stressors and medication use.

Sustaining Strong Immunity

  • Do not smoke. A host of nutrients are depleted through cigarette smoking, but the destruction of innate immune defence structures in airways is extremely problematic for smokers.
  • Exercise regularly, but not in the extreme. Exercise that is extreme enough to cause stress on the body can act as a stressor, releasing cortisol (an immune suppressant). Exercise that depletes muscle mass is known to deplete the immune system.
  • Healthy weight maintenance. This is not only in regards to weight loss, but losing excess fat as opposed to lean body mass (muscle) and gaining weight (both fat and muscle mass) in those who are underweight. Both healthy fat and protein stores in muscle are essential for strong immune health.
  • Without question, healthy and restful sleep is protective for your immune system. Without adequate rest, we do not recover well from infection; we run our body on energy reserves and do not give our body adequate time to repair damage whilst asleep.
  • Micronutrient malnutrition is extensive, even in affluent countries and societies. A diet low in variation (common in children and the elderly) is one possible cause. The quality of foods ingested, or a diet high in processed foods is another. Diets low in protein are renowned for compromising the immune system.
  • The minerals zinc, selenium, iron and copper are all very important for sustaining healthy immune responses. In terms of vitamins, A, D, E, B2, B6 and C all support accurate immune responses in animal studies.

Written for and published by the MINDD Foundation: www.mindd.org

Image credit: Biology Questions and Answers

References
1. Alberts, B. et al. (2002). Molecular Biology of the Cell (4th Ed). Chapter 24: The Adaptive Immune System. Garland Science, New York.

2. Kau, A. et al. (2011). Human nutrition, the gut microbiome and the immune system. Nature. 474: 327-336.
Lange, T. et al. (2010). Effects of sleep and circadian rhythm on the human immune system. Annals of the New York Academy of Sciences. 1193: 48-59.

3. Legrand, N. et al. (2006). Experimental models to study development and function of the human immune system in vivo. Journal of Immunology. 176 (4): 2053-2058.

4. Segerstrom, S. et al. (2004). Psychological stress and the human immune system: a meta-analytic study of thirty years of enquiry. Psychological Bulletin.

5.  Wiesner, J. and Vilcinskas. A. (2010). Antimicrobial peptides: the ancient arm of the human immune system. Virulence. 1 (5): 440-464.