“The health of the gut and its immune system is a fundamental factor for me to assess with every patient. Why? The gut and immune system are intimately related in their interactions and if they are not performing as they should then this can negatively influence the overall health of the person.” So commented Dr Rangan Chatterjee when we interviewed him for our blog in January of this year (‘Practicing Good Medicine’).
An Introduction to Dr Rangan Chatterjee
‘Doctor in the House’ – BBC1
It is wonderful to see that Dr Rangan Chatterjee is now on prime-time BBC 1 in the new three-part health series ‘Doctor in the House’. Having spent 6 years as a hospital doctor and the last 7 years working in General Practice around Manchester we wrote that he had “developed a ‘nutrition based’ methodology when engaging with his patients. His passion is to get to the root cause of problems rather than to just treat symptoms. He specialises in gut health and the immune system, and these areas plus nutrition typically form the core of his new patient consultation and treatment.”
We can now all fortunately see the evidence of this approach in the BBC series which “sees three normal families inviting a doctor into their lives for two months, to undergo the health MOT of a lifetime. Throughout the GP does not prescribe any drugs and only administers, when necessary, vitamins and supplements.”
Cytoplan Seminar, 25th September 2015 – Dr Chatterjee provides a talk on ‘Gut Health’
Dr Chatterjee studies at the Institute of Functional Medicine (IFM) in the USA. We were fortunate enough to have him speak at one of our health practitioner events in September of this year with his topic being ‘Gut Health’. He shared with his audience a wealth of scientific knowledge and practical experience in the management of the gut microbiome and the integral role this plays in the health of the body. Dr Chatterjee discussed scientifically proven live native bacteria therapy and specific dietary interventions for the health of the gut and the immune conferring benefits for the body.
Our gut is intimately linked with our immune system and all other bodily functions, for example producing around 90% of the neurotransmitter serotonin, which has the most profound effect on mood. So with Dr Chatterjee demonstrating his approach of “practicing good medicine” to a wider audience via the BBC it seems timely to review some of the topics he covered in September.
In today’s article we cover the twin topics of vitamin A, plus the ‘aryl hydrocarbon receptor’ (AhR) – and their importance to gut health and consequently to immunity. In our concluding article next week we cover live native bacteria supplements; recent research on specific gut bacteria and foods that promote their activity; the effects of short-chain-fatty-acids in the gut; and the relevance of apples to selective gut health.
Gut health and the Immune System – The role of Vitamin A
Our immune system is essentially and intimately linked with our gastro-intestinal system; so if the latter is performing poorly it will impact on the former. We all know that what we eat and drink is so important to our health. In his talk Doctor Chatterjee discussed particular aspects of our diet, for example food combinations, that research has shown to be beneficial to gut and immune health.
In particular he covered vitamin A and its immune modulating effects in the gut. And he expanded on how retinoic acid can tune multiple aspects of the immune response, particularly in relation to the small intestine, immune tolerance, and adaptive immunity.
Indeed vitamin A has the permitted health claim of ‘contributing to the normal function of the immune system’.
Forms of Vitamin A
We obtain vitamin A from diet, either from plant foods (Provitamin A carotenoids) or from animal derived foods (Preformed Vitamin A – retinol and retinyl ester).
The body converts Provitamin A carotenoids, the most important of which is beta-carotene, to vitamin A. Both provitamin A and preformed vitamin A are metabolised in the small intestine to retinol and retinal, the active forms of vitamin A. Retinol is the form in which vitamin A is stored, retinal is important for vision. Finally there is also retinoic acid which has hormone-like effects.
Prevalence of low levels of vitamin A
In his presentation Doctor Chatterjee noted the following research:
“In the U.K., 50% of men and 49% of women do not meet current national recommendations for preformed vitamin A when other provitamin A sources are not taken into consideration.
Thus, people with reduced ability to convert provitamin A sources to active vitamin A could be susceptible to wide-ranging health risks. This is especially important since recent research indicates that approximately 40% of all Europeans possess a gene variant that restricts the amount of beta-carotene their bodies can utilise and convert into vitamin A.”
The genetic variation referred to is called a Single Nucleotide Polymorphism (SNP). A SNP may change the structure and function of a gene. For example one of the most discussed SNPs, MTHFR, affects how the body metabolises folic acid.
A study in relation to provitamin A conversion and certain SNPs “further demonstrates that provitamin A metabolism is influenced by multiple SNPs and that genetic variability should be taken into account in future recommendations for provitamin A supplementation”. One of the SNPs referred to is BCMO1. This is a gene which codes for a key enzyme in beta-carotene metabolism. The consequence of this SNP is a 48% reduction in enzyme activity.So if BCMO1 results in compromised conversion of beta-carotene, vegetarians and vegans in particular may be at increased risk of low levels of vitamin A.
The role of Vitamin A in maintaining Immune System health
Vitamin A has a role in both the innate and adaptive immune systems. In the innate immune system it helps regeneration of mucosal barriers and supports the function of neutrophils, macrophages, and natural killer cells. Vitamin A is also required for adaptive immunity and plays a role in the development of both T-regulatory cells and B-cells.
Retinoic acid, is important in immune tolerance this means that we are able to:
- consume a wide variety of foods (ie foreign substances) and not react to them;
- tolerate the commensal microbes in our gut and finally;
- tolerate ourselves!
Our gut immune system is exposed to more antigens in a single day than the systemic immune system meets in a lifetime. Vitamin A does this by promoting the production of T-regulatory cells – these help quench inappropriate inflammation from other immune cells, specifically Th1, Th2 and Th17 cells.
“Although it was originally thought to have a selective role in the induction of tolerance, it is now clear that the effects of retinoic acid on adaptive immunity are context dependent and that it can tune multiple aspects of the immune response.”
An example given as part of the talk was research demonstrating the increased absorption of vitamin A if eaten with healthy fats; in this specific example an avocado. The research study compared a raw carrot eaten alone with one eaten with the addition of one avocado. Compared to a raw carrot meal without avocado, the addition of one avocado (150 g) showed:
- Significantly increased beta-carotene absorption 6.6 times
- More than quadrupled (4.8 times) alpha-carotene absorption
- Significantly increased (12.6 times) the conversion of provitamin A (inactive vitamin form) to vitamin A (active vitamin form)
The Aryl Hydrocarbon Receptor
Continuing the themes of gut health in relation to diet and genes Doctor Chatterjee talked about the ‘aryl hydrocarbon receptor’ (AhR) and its importance to gut health and consequently to immunity. And in particular foods that cause AhR to be ‘expressed’. A range of research confirms the importance here towards gut and immune health, for example in support of IBS sufferers.
The ‘aryl hydrocarbon receptor’ is a protein that in humans is encoded by the AhR gene. Intraepithelial cells (IELs) from the intestines and skin express especially high levels of AhR. IELs defend against assaults from the environment. Essential functions of these cells include promoting epithelial repair following injury and limiting epithelial cell invasion by commensal bacteria that inhabit the gut. AhR signalling is required for IEL maintenance in the intestinal epithelium.
There are a number of ligands that activate AhR. A ligand is a molecule that binds to a receptor and elicits a response. Our diet contains a number of ligands for the AhR receptor including the phytochemical indole-3-carbinol which is found in cruciferous vegetables such as broccoli and cabbage; flavonoids such as quercetin, which is found in apples and resveratrol which is found in red wine.
Research has commented that “AhR is joining the ranks of other regulatory proteins critical for the development and maintenance of crucial components of the immune system, including gut-associated lymphocytes that mediate mucosal immunity”.
As such specific dietary compounds found at high levels in vegetables such as broccoli and cauliflower are essential for sustaining intestinal immune function. Moreover they show that the molecular basis for this link involves the aryl hydrocarbon receptor.
A problem here may be low stomach acid. Dietary compounds, such as indole-3-carbinol (I3C) from cruciferous vegetables are converted into high affinity AhR ligands after encountering the acid environment of the stomach. This is therefore another mechanism by which low stomach acid (eg due to antacids or age) could have a negative effect on gut health.
In closing on the topic of diet and AhR Doctor Chatterjee included a prescient quote from the research paper “You AhR what you eat: linking diet and immunity” (Hooper LV).
“From childhood we learn that vegetables are good for us, and most of us eat our veggies without giving much thought to the evidence behind this accepted wisdom or to the mechanisms underlying the purported health-boosting properties of a vegetable-rich diet. …… a link between diet and immunity, showing that specific dietary compounds found at high levels in cruciferous vegetables such as broccoli, cauliflower, and cabbage are essential for sustaining intestinal immune function. Moreover, they show that the molecular basis for this link involves the aryl hydrocarbon receptor (AhR).”
Dr Rangan Chatterjee qualified from Edinburgh University Medical School in 2001 and has been practising medicine ever since. He has completed Membership for the Royal College of Physicians as well as Membership for the Royal College of General Practitioners. Initially, he worked as a hospital doctor for 6 years and has spent the last 7 years working in General Practice. Rangan also holds a BSc Honours Degree in Immunology and is a member of the Institute of Functional Medicine in the United States where he has undergone extensive training. You can find out more about him on his website.
If you have any questions regarding the health topics that have been raised, or any other health matters please do contact me (Amanda) by phone or email at any time.
firstname.lastname@example.org, 01684 310099
Amanda Williams and the Cytoplan Editorial Team: Joseph Forsyth, Simon Holdcroft and Clare Daley
References are available upon request.