Part 3 in the 7 part series: For king and country – tend to your immune system

This article was originally published as a guest editor post at foodpharmacy.se

By: Graeme Jones, clinical physiologist and CEO at Nordic Clinic Stockholm. (Thanks to Annie Pettersson, Nordic Clinic’s Researcher, for her contribution to the article)

Published: 23/04/2020

I moved to Sweden from the U.K. and arriving in April I was met with an interesting sight. As soon as the sun popped out, people would pose like statues, their faces facing the sun and their eyes shut. Leaning onto walls in the middle of the street, on top of a bridge, at the bus stop. I wondered what the hell are they doing? It took but one year of darkness, and the upcoming April I was standing there like the rest of them. 

Our worship of the sun isn’t limited to its role as a symbol for the coming of summer, nor to the fact that it’s essential to our survival by bringing life into plants and animals, that we eat. I believe many with me can agree that they simply feel good when they’re exposed to the sun. As we shall see, there are several reasons for this.

Until now it hasn’t been problematic for our species, evolutionary speaking, to be dependent on sun exposure for important biological functions, since indoor life is a new phenomenon and a lack of sun exposure hasn’t been an issue for the vast majority of mankind. Humans colonised the far northern hemisphere some 4 000-30 000 years ago (depending on location), but that’s not considered very long in evolutionary terms. Also, those populations were exposed to the sun half of the year, whereas us modern Homo sapiens tend to spend a huge chunk of our time indoors in the summer as well. Let’s have a look at how we’re affected by those golden rays.

The Sunshine Vitamin

The most well-known effect of sun exposure is vitamin D production. It’s a hormone-like cholesterol derivative that we can also get through our diet (fatty fish mostly, like salmon). Vitamin D is not actually made in our skin, but a precursor is produced from cholesterol with ultraviolet B (UVB) exposure, which then travels to the liver for modification and is transformed into the active form called calcitriol, mainly in the kidneys. This molecule controls the use of hundreds, maybe thousands of genes, a whopping 3% of our genome. (1, 2) Many of these genes are involved in optimising our immune system by 1) helping it fight infections and cancer and 2) keeping the immune system under control by preventing it from overreacting, thus limiting autoimmune disease. (2)

The importance of this molecule cannot be stressed enough. Vitamin D deficiency correlates with virtually every type of immune-related disorder there is (including cancer, autoimmune disease, cardiovascular disease, metabolic disease and depression) where the link has been investigated scientifically. Also, vitamin D is essential for mineral balance and to avoid osteoporosis, a serious disease causing weakening of the bones. These conditions are more common in people self-reporting to stay out of the sun, and/or who live further away from the equator. Correlation studies warrant caution: a mere epidemiological association does not imply causation. However, the observed connection between vitamin D and chronic disease and inflammation is supported by experimental evidence – a higher level of evidence. This means that disease risk, symptoms or clinical markers have been shown to improve in humans or animals that get vitamin D or are exposed to UV radiation. (2, 3, 4)

Nitric Oxide – The New Kid On the Block 

When UVA hits our skin, nitric oxide (NO) is made. NO has traditionally been viewed as a free oxygen radical, a damaging molecule. But NO also has important functions in relaxing and dilating our blood vessels. Some researchers suggest that UV-induced NO has the same effect. In accordance, NO from sun exposure seemingly leads to a reduction in blood pressure, according to some pioneering studies. Formation of NO is the reason beetroot juice and arginine supplementation can be so powerful in alleviating hypertension. Further, some researchers suggest that NO can kill infectious microbes and tumor cells, promote wound healing, and also works as a neurotransmitter. Early studies support the idea that many of the positive effects we see of sun exposure is not, in fact, vitamin D dependent, but can be attributed partly to NO. (5, 6) 

Endorphins and Serotonin Relieve Stress and Pain and Enhances Mood

Sun exposure has been linked to a heightened mood, relaxation and reduced tension. When skin cells are exposed to UV radiation, beta-endorphins get released into the blood, possibly in levels that affect our brains and well-being. Beta-endorphins are formed by neurons and exert stress-reducing and pain-lowering effects. Our nervous system also produces serotonin, a production which is increased with sunlight exposure of the skin and the eyes. Serotonin is a neurotransmitter that has many effects, including increasing a sense of calm and joy. Fibromyalgia sufferers report lower pain after UV radiation, and depression is also improved by sun exposure. The mood boost and analgesic effects might be partly due to beta-endorphins and serotonin, and partly to vitamin D. (1, 7-9)

A Lack of Daylight Impairs Circadian Rhythm

Exposure of the eyes to light also affects melatonin secretion. Melatonin is our sleep hormone, usually secreted at a specific daily rhythm, with low levels at daytime and a peak around midnight. When and how much is influenced by the amount of exposure to light during the day. Our circadian rhythm is very important not only for sleep, but also for our metabolic health and our risk of cancer and cardiovascular disease. Melatonin is also an antioxidant with anti-carcinogenic effects. (1, 10)

Sun Exposure Lowers Our Risk of Suffering and Death

You may find this subheading somewhat provocative. However, it is essentially true. As we’ve learned, sun and vitamin D lowers risk of inflammatory conditions of all thinkable kinds. Furthermore, many skin conditions (eczema, vitiligo, psoriasis and more) improve upon sun exposure or UV therapy, through many suggested mechanisms. Also, the risk of a long list of cancer types is seemingly lower in those who are exposed to more sun. (3, 10, 11) The risk of a long list of cancer types… Please take a moment to contemplate this fact.  

Findings are not unanimous (research seldom is) but overall, studies of different types point toward a protective role of sun exposure and/or vitamin D levels when it comes to cancer. These studies involve both observational and experimental studies. One review concludes: “The UVB–vitamin D–cancer hypothesis has considerable supporting scientific evidence from a variety of study types: geographical ecological, observational, and laboratory studies of mechanisms, as well as several clinical trials. At this time, the general public and individual physicians can spend more reasonable time in the sun and use vitamin D3 to prevent and treat many cancers.” (11)

Vitamin D is also associated with a lowered all-cause mortality. The risk of death is inversely correlated with the concentration of  vitamin D in the blood, up to a certain level. Vitamin D deficiency is not only a risk factor for increased mortality per se, but vitamin D supplementation may also reduce mortality. (1)

Overall, the diverse effects of the sun on our health is striking. I wouldn’t be surprised if new, currently unknown mechanisms of sun-derived biological effects will be uncovered in the years to come. Caution is warranted: consensus is that we strictly must avoid burning the skin, and be moderate regarding our sun exposure. UV radiation also degrades folate, so please ensure sufficient folate intake during the summer months. (1, 2) However, if you’re staying out of the sun to protect yourself from skin cancer, you might want to rethink your strategy and consider your health on the whole. Also, if you’re trying to replace the sun with vitamin D supplementation, be aware of the many other benefits you miss out on. Maybe you’ve heard of the classic ladder of basic human needs. Perhaps it’s time we update that list to air, food, water, shelter, and sun.

If you want to talk to me more about any part of this article, please contact me on info@nordicclinic.se or read more here on our website.

You find the other articles in the 7 part series ”For king and country – Tend to your immune system” here:

Part 1: Your Immune System is Everything

Part 2: The Surprising Connection between the Gut Mocrobiome and Infections in other Organs

References

1. Trummer et al Int J Environ Res Public Health. 2016 Oct; 13(10): 1028. Beneficial Effects of UV-Radiation: Vitamin D and beyond
2. Carlberg C. Nutrients. 2019 Mar 21;11(3). Nutrigenomics of Vitamin D.
3. Hart et al. Annu Rev Pathol. 2019 Jan 24;14:55-81. Exposure to Ultraviolet Radiation in the Modulation of Human Diseases
4. Gorman et al. Photochem Photobiol Sci. 2017 Mar 16;16(3):362-373. Ultraviolet Radiation, Vitamin D and the Development of Obesity, Metabolic Syndrome and type-2 Diabetes
5. Juzeniene and Moan. Dermatoendocrinol. 2012 Apr 1; 4(2): 109–117. Beneficial effects of UV radiation other than via vitamin D production
6. Holliman et al, Ken Raj. Sci Rep. 2017 Sep 11;7(1):11105. Ultraviolet Radiation-Induced Production of Nitric Oxide:A Multi-Cell and Multi-Donor Analysis
7. Mead, M.N. Environ Health Perspect. 2008 Apr; 116(4): A160–A167. Benefits of Sunlight: A Bright Spot for Human Health
8. Veleva et al. Photodermatol Photoimmunol Photomed. 2018 Sep;34(5):288-297. Effect of ultraviolet light on mood, depressive disorders and well-being.
9. Stewart et al. Med Hypotheses. 2014 Nov;83(5):517-25. Possible contributions of skin pigmentation and vitamin D in a polyfactorial model of seasonal affective disorder.
10. van der Rhee et al. Med Hypotheses. 2016 Dec;97:34-37. Regular Sun Exposure Benefits Health
11. Grant, W. A Review of the Evidence Supporting the Vitamin D-Cancer Prevention Hypothesis in 2017. Anticancer Research February 2018 vol. 38 no. 2 1121-1136

Part 2 in a 7 part series: For king and country – tend to your immune system

This article was originally published as a guest editor post at foodpharmacy.se

By: Graeme Jones, clinical physiologist and CEO at Nordic Clinic Stockholm.

Published: 15/04/2020

Extensive research is currently underway looking at the role that the gut microbiota – all the microorganisms in the intestinal tract – plays in overall health. As we’ll learn in this article, there is a link between the gut flora and immune health. But let’s start with the connections found between gut microbiota and brain health. 

In the early stages of gut microbiome research, scientists linked gut health to brain health through a major communication ‘highway’ called the vagus nerve, which travels from the digestive tract to the brain (think of it like a direct telephone line). This nerve, which influences everything from our mood to our immune response, digestion and heart rate, exerts a relaxation effect – it slows your heart rate, decreases blood pressure, improves your mood and coordinates digestion. “Sign me up for more of that”, I hear you say, “can I install a second telephone line?” Well no, sorry, but we can stimulate it through various techniques – more on that later. That is why it has been the target of treatment for major depression, post traumatic stress disorder and inflammatory bowel disease, amongst others. It has also shown as a conduit through which the gut microbiota mediates effects on the brain. So our digestive bacteria ‘talk’ to our brain through this direct ‘phone line’? Bullseye! 

With the continuous and alarming escalation of dementia worldwide and no pharmaceutical cure in the pipeline (many pharmaceutical companies have just completely dropped the development of Alzheimer’s medication), of great interest are further reports that the microbiota play a role in the pathogenic cascade of both Parkinson and Alzheimer diseases (1). With all this research, it has led to a commonly accepted term called the gut-brain axis, but we are now discovering this was barely a scratching of the surface. While scientists were digging into this axis, they discovered many more communication ‘highways’ or ‘axes’, where information travels back and forth to coordinate a whole host of activities in the body. Some of these bi-directional axes include:

• Gut-liver axis
• Gut-bone axis
• Gut-immune axis
• Gut-muscle axis
• Gut-fat axis
• Gut-lung axis
• Gut-heart axis

Could these billions of bacteria living in our gut play a role in how distant organs and tissues function? Yes, it seems! The vagus nerve ‘direct line’ is only one part of this puzzle, so let’s dive into some of the other communication tools these sneaky little bugs use in our intestinal tract. 

Our microbes mobile phone equivalent

If we think of the gut bacteria influencing the vagus nerve as a sort of ‘old school direct telephone cable line’ to the brain, then what other methods of communication can they use across the different axes? By-products produced by the microbes in our intestines are called microbial metabolites and they are released from the gut. They include two key metabolites called secondary bile acids and short-chain fatty acids. Think of these like using a mobile phone network instead of a direct line to communicate with different tissues. The first, bile acids, break down and aid absorption of fat from our diet whilst the second, short-chain fatty acids, are produced by beneficial bacteria when we eat fibre and make their way to the brain. This is one of the reasons why a high fibre diet could be very important for brain health.  

Gut-Immune Axis

As we are discovering, these gut microbes have different communication channels they can pull on to talk to the different tissues. Since the gut microbiome also has a powerful effect on the immune system via the gut-immune axis, might this whopping 2 kg of microbes living in our intestines help modulate infection risk in some of these other tissues? Let’s look at some of these connections.

The Heart

Myocarditis is inflammation of the heart and typically occurs due to viral infection. Using mouse models of autoimmune myocarditis, researchers have discovered that modulating the gut microbiome may be a novel target for improving outcomes (2).

Another paper found that excessively activating immune cells in the gut exacerbates myocarditis in mice, progressing to mortality (3). Additionally, T cells (an important part of our immune defence system) in humans with myocarditis were more reactive to Bacteroides thetaiotaomicron (a common bacteria found in the gut) than those from healthy controls. This data implies that mortality from myocarditis may be partly regulated by the state of the microbial ecosystem in the gut. 

Lung infections

Viral respiratory infection severity often worsens with secondary infections that may arise from the gut. A study in mice found that influenza A infection causes changes in the gut microbiome that, upon transfer to healthy mice, impairs defense to pneumococcal infection (4).  Pneumococcal infection is caused by a type of bacteria called streptococcus pneumoniae, which can affect the lungs – now you know why it is called pneumonia. This means that in mouse models, getting the flu can cause changes in the gut bacteria and this subsequently decreases defence to a lung infection.

In older humans it has been shown that antibiotic treatment alters immunity to vaccination by decreasing specific influenza antibodies (5), meaning antibiotics may decrease our ability to fight influenza viruses as we get older. Interestingly, treatment with antibiotics increased the inflammatory response through loss of secondary bile acids (which I talked about earlier in this article) created by members of the gut microbiome.

Bloodstream infections (BSI)

For decades, some brave souls in medicine have been pushing for more research into whether ‘leaky gut’, describing the translocation of bacteria from the intestine into the bloodstream, actually occurs.  The standard medical establishment has viewed this as quackery, until research has slowly caught up actually showing this can and does happen under various disease states and circumstances such as type II diabetes, high fat diets and alcohol consumption, to name a few. At Nordic Clinic, where we deal with patients who suffer from chronic health conditions, in subsets of patients we can often test and find they have resident bacteria from the oral and digestive cavity present in the bloodstream!  

One of the most severe and worrying conditions I can think of is sepsis, where the body’s response to infection causes injury to its tissues and organs. Several studies have successfully used tests to show bacterial and fungal toxins from the gut present in the bloodstream, mostly in patients with this condition (7). And intestinal barrier dysfunction, where the digestive tract becomes hyperpermeable (a better term for ‘leaky gut’), is thought to contribute to the development of multiple organ dysfunction syndrome in sepsis (8). 

Enhanced levels of bacterial toxins are also found in patients with obesity and metabolic syndrome (9,10) which might indicate bacterial translocation from the gut lumen into circulation as a consequence of intestinal barrier function failure causing ‘leaky gut’. As I say time and time again, looking after your metabolic health is so important for gut health and vice versa. 

Middle Ear Infections in children

Many parents I am sure can relate to spending hours at the doctor’s surgery for their child’s ear infections. It is caused by bacteria that travel and make their way from the upper part of the throat, through canals (called Eustachian tubes), to the middle ear. Symptoms include fever, earache, and occasionally the eardrum may perforate, discharging pus into the ear canal.

Antibiotics are often prescribed for acute middle ear infection, although they have only a modest effect on reducing symptoms. Moreover, excessive antibiotic use leads to antibiotic resistance (a very worrying side-effect of use), making them less effective for these and other possible future infections. Consequently, preventing acute middle ear infection is highly desirable over treatment. According to Cochrane Reviews website, whose work is internationally recognized as the benchmark for high-quality information about the effectiveness of healthcare, probiotics may prevent ear infections in children not prone to it (11). This suggests there is a possible link between a substance (probiotic bacteria) that modulates the gut microbiome and the prevention of ear infections. 

Urinary Tract 

UTI (Urinary Tract Infection), is one of the most common types of infection affecting over 150 million people yearly (12).  A recent study found that digestive tract abundances of Escherichia and Enterococcus (families of bacteria that live in the gut) are associated with future development of Escherichia and Enterococcus urinary tract infection, respectively, independent of clinical factors like gender (13).  These microbes do not seem to discriminate between the sexes, and the gut seems to be the ‘headquarters’ from which infection can possibly arise. 

Reduce the risk of infection by cultivating a healthy gut microbiome

By various methods, our gut microbes are able to communicate with a whole variety of tissues, organs and glands. A large body of research evidence is growing demonstrating how important it is to have optimal gut health, function, bacterial balance, and a robust intestinal barrier to ensure a reduced risk of many other types of infection, syndromes and diseases. A viable strategy may be that we all should be monitoring our gut microbial communities on a yearly basis, like we do with our cars as they age – it is always more effective to prevent rather than cure. 

Infection has and will continue to happen to all of us, it is an inevitable part of being alive in this biodiverse ecosystem we call Earth. However, we can possibly reduce our risk of infection, or infection being very problematic, by cultivating our own healthy gut microbiome ecosystem and improving the gut-immune axis. How to actually do this is a large topic in itself to save for another future blog post.

If you want to talk to me more about any part of this article, please contact me on info@nordicclinic.se or visit www.nordicclinic.se or www.nordicclinic.com to read more.

References

1. Friedland, R. P., & Chapman, M. R. (2017). The role of microbial amyloid in neurodegeneration. PLoS pathogens, 13(12), e1006654. https://doi.org/10.1371/journal.ppat.1006654
2. https://www.ncbi.nlm.nih.gov/pubmed/30508676
3. https://science.sciencemag.org/content/366/6467/881.abstract
4. https://www.sciencedirect.com/science/article/pii/S2211124720301674
5. https://www.sciencedirect.com/science/article/pii/S0092867419308980
6. https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-016-0301-4
7. Bates, D. W., Parsonnet, J., Ketchum, P. A., Miller, E. B., Novitsky, T. J., Sands, K., … & Kahn, K. (1998). Limulus amebocyte lysate assay for detection of endotoxin in patients with sepsis syndrome. Clinical infectious diseases, 27(3), 582-591.
8. Yoseph, B. P., Klingensmith, N. J., Liang, Z., Breed, E. R., Burd, E. M., Mittal, R., Dominguez, J. A., Petrie, B., Ford, M. L., & Coopersmith, C. M. (2016). Mechanisms of Intestinal Barrier Dysfunction in Sepsis. Shock (Augusta, Ga.), 46(1), 52–59. https://doi.org/10.1097/SHK.0000000000000565
9. Bergheim, I., Weber, S., Vos, M., Krämer, S., Volynets, V., Kaserouni, S., … & Bischoff, S. C. (2008). Antibiotics protect against fructose-induced hepatic lipid accumulation in mice: role of endotoxin. Journal of hepatology, 48(6), 983-992.
10. Thuy, S., Ladurner, R., Volynets, V., Wagner, S., Strahl, S., Königsrainer, A., … & Bergheim, I. (2008). Nonalcoholic fatty liver disease in humans is associated with increased plasma endotoxin and plasminogen activator inhibitor 1 concentrations and with fructose intake. The Journal of nutrition, 138(8), 1452-1455.
11. https://www.cochrane.org/CD012941/ARI_probiotics-healthy-bacteria-preventing-acute-middle-ear-infection-children
12. Stamm, W. E., & Norrby, S. R. (2001). Urinary tract infections: disease panorama and challenges. The Journal of infectious diseases, 183(Supplement_1), S1-S4.
13. Magruder, M., Sholi, A. N., Gong, C., Zhang, L., Edusei, E., Huang, J., … & Dadhania, D. M. (2019). Gut uropathogen abundance is a risk factor for development of bacteriuria and urinary tract infection. Nature communications, 10(1), 1-9.

Part 1 in a 7 part series: For king and country – tend to your immune system

This article was originally published as a guest editor post at foodpharmacy.se

By: Graeme Jones, clinical physiologist and CEO at Nordic Clinic Stockholm.

Published: 10/04/2020

The immune system is all over the news these days. Its antiviral functions get all the attention but there are good reasons to consider the entire immune system, with its full range of functions. Its condition is one of the most important factors determining health and disease overall. Now’s the time to appreciate the importance of nurturing our immune systems, not only to withstand acute infections but also some of the most dreaded diseases of the modern world.

The often ignored causes of autoimmune disease

While infections bring to mind runny noses, fevers and sore throats, you may be surprised to learn that they  can cause a vast number of conditions. Autoimmune disease happens when the immune system attacks our own tissues by mistake. Researchers are well aware that autoimmune conditions like lupus (1), rheumatoid arthritis (2), multiple sclerosis (3), inflammatory bowel disease (4), thyroid disease (5), ankylosing spondylitis (6), OCD and PANDAS (7) and many more can be triggered by viruses, bacteria, fungi, or parasites (8). In other words, a well functioning anti-infectious immune system also protects us against autoimmune disease. Neuropsychiatric disorders such as autism, schizophrenia and psychosis, thought by some to have an autoimmune component, can also be triggered by infections, sometimes maternal infections while in the womb (9-12).

Uncontrolled immune cells can also take part in the development of autoimmune disorders, even when there seems to be no infection. This happens when failsafe mechanisms and built-in immune suppression don’t work, and when inflammation is too high which might result from any or several out of a wide range of lifestyle and environmental factors. (13)

Cancer – when immune function fails

Unknown to many, infections can cause cancer. It’s a well established fact that the human papillomavirus can cause cervical cancer, but this is not the only infection-cancer connection. In fact, examples are numerous. (14) Moreover, immune cells are normally able to recognise and destroy cancerous cells; tumor growth and metastases is what happens when they fail. Immunotherapy is already highly successful in treating some cancers. Immunotherapy means stimulating the immune system to enhance its inborn ability to detect and destroy cancerous cells. (15) However, an even more successful strategy might hypothetically be to optimise normal immune function, even before cancer grows and spreads. 

Depression is caused by inflammation

Depression is highly associated with inflammation. There are many possible reasons we might be inflamed, and one of them is infection. When researchers inject lipopolysaccharides (bacterial toxins) into mice, or interferon gamma (a protein which helps the immune system deal with infections) into human study participants, mimicking an infection, the rodents and participants often develop symptoms of depression, and rather rapidly. (16, 17, 18)

A proinflammatory diet, sedentary lifestyle and excessive stress all increase inflammation as well, which affects the brain and the immune system: where there’s inflammation, the immune system is always involved one way or the other. (19)

ME/CFS – immune dysfunction in every sense

The devastating condition myalgic encephalomyelitis (often called chronic fatigue syndrome, or ME/CFS for short) has multiple potential causes but often starts with an infection. (20) Researchers have also observed immune dysfunction in these patients. Some of them fail to mount an appropriate immune response, meaning they have a hard time fighting off infections.

Does everything come down to the immune system in the end?

Even type 1 diabetes (21), IBS (22), Alzheimer’s disease (23), and cardiovascular disease (24) ‒ while multifactorial, of course ‒ have been connected to infection and/or to immune dysfunction. And when a clear infection isn’t involved in the pathogenic course, an imbalanced or overgrown gut flora is often implicated, which plays an intricate game with the immune system and may exert a central impact on the conditions listed above of a magnitude equal to infections. 

That’s an impressive list of conditions, covering the majority of health conditions known to mankind. 

To sum up, the anti-infectious and self-regulating operations of our immune system may be critical to protect ourselves from diseases that surround us every day. Diseases that dramatically decrease our quality of life, but may be preventable.

It all makes one wonder. Why do some people develop ME/CFS or lifelong autoimmune disorders from an infection that we’re supposed to be able to clear, or at least bounce back from once it’s been treated? What distinguishes those who catch every infection that comes along from those who sail through life with little more than the occasional bout of the sniffles? Why do cancerous tumours dissolve in some while they grow, and spread, in others?

I’m going to stick my neck out: if you have a well-functioning immune system, supported by a healthy lifestyle, most infections are not supposed to cause lifelong disease. The system is supposed to do its job and then sit right down again. If it does not, something is wrong, and the evidence that the status of our immune system means everything in terms of disease prevention mounts to levels that we can’t (and shouldn’t) ignore. 

Genetic susceptibility does play some part (25), that much is undeniable. However, as we shall see in this seven part series, environmental, behavioural and lifestyle factors all have a massive impact on immune function.

This is paramount. The largest part of our health care budget is spent on pharmaceutical management of chronic disease. That strategy is expensive, ridden with side-effects and shockingly underwhelming in terms of health outcomes. By taking to heart that immune function and lifestyle choices are at the very centre of our well-being, and adapting medical interventions thereafter, we can free national economic resources so large that anyone would gasp at the insight.

So how you and I care for our immune systems affects not only our own quality of life, our happiness and longevity, but society as a whole.

In the upcoming article series I’ll guide you through the most important ways the immune system is strengthened or burdened, and how to adjust your lifestyle to help it work as well as it possibly can. I’ll address the profound effects of stress, sleep, physical activity and diet on immune function. Furthermore, we’ll learn about the surprising links between joy, humour, sun exposure, gut flora and optimal immune health.

The good news is that most interventions are free of both cost and side effects. By reversing chronic disease or reducing its likelihood, you also reduce your own expenses for medication, doctor’s visits and sick leave. This is what’s known as a “win-win-win situation”. We all win – your health and happiness, your wallet and your fellow human beings. 

So for yourself, your neighbour, your king and country – tend to your immune system!

References

1. Connie C. Qiu, Roberto Caricchio, and Stefania Gallucci. Front Immunol. 2019; 10: 2608. Triggers of Autoimmunity: The Role of Bacterial Infections in the Extracellular Exposure of Lupus Nuclear Autoantigens

2. Song Li, Yangsheng Yu, Yinshi Yue, Zhixin Zhang, and Kaihong Su. Microbial Infection and Rheumatoid Arthritis. J Clin Cell Immunol. 2013 Dec; 4(6): 174.

3. Mariano Marrodan, Lucas Alessandro, Mauricio F Farez, Jorge Correale. Mult Scler, 25 (7), 891-901 Jun 2019 The Role of Infections in Multiple Sclerosis

4. Mann EA, Saeed SA. Curr Opin Gastroenterol. 2012 Jan;28 (1):24-9. Gastrointestinal infection as a trigger for inflammatory bowel disease.

5. Deirdre Cocks Eschler, Alia Hasham, and Yaron Tomer. Clin Rev Allergy Immunol. 2011 Oct; 41(2): 190–197. CUTTING EDGE: THE ETIOLOGY OF AUTOIMMUNE THYROID DISEASES

6. Li Zhang, Yan-Jie Zhang, Jin Chen, Xiao-Lei Huang, Gong-Si Fang, Li-Juan Yang, Yu Duan, Jing Wang. Microb Pathog 117, 49-54 Apr 2018. The Association of HLA-B27 and Klebsiella Pneumoniae in Ankylosing Spondylitis: A Systematic Review

7. Kyle A Williams, Susan E Swedo, Brain Res, 1617, 144-54, 2015 Aug 18. Post-infectious Autoimmune Disorders: Sydenham’s Chorea, PANDAS and Beyond

8. Ercolini AM, Miller SD. Clin Exp Immunol. 2009 Jan;155 (1):1-15. The role of infections in autoimmune disease.

9. Rose Jeppesen and Michael Eriksen Benros. Front Psychiatry. 2019; 10: 131. Autoimmune Diseases and Psychotic Disorders

10. Benros ME, Mortensen PB. Curr Top Behav Neurosci. 2020;44:141-159. Role of Infection, Autoimmunity, Atopic Disorders, and the Immune System in Schizophrenia: Evidence from Epidemiological and Genetic Studies.

11. Paul H. Patterson. Trends Mol Med. 2011 Jul; 17(7): 389–394. MATERNAL INFECTION AND IMMUNE INVOLVEMENT IN AUTISM

12. Estes ML, McAllister AK. Science. 2016 Aug 19;353(6301):772-7. Maternal immune activation: Implications for neuropsychiatric disorders.

13. Mousumi Chakraborty, Elena Shashkova, Anna Cline-Smith and Rajeev Aurora. Disruption of self-tolerance in autoimmune diseases and therapeutic modulation to restore immune balance. J Immunol May 1, 2018, 200 (1 Supplement) 175.12

14. David H. Persing, Franklyn G. Prendergast. INFECTION, CANCER, AND THE IMMUNE RESPONSE.  National Academies Press

15. Pankita H. Pandya, Mary E. Murray, Karen E. Pollok, and Jamie L. Renbarger  J Immunol Res. 2016: 4273943. The Immune System in Cancer Pathogenesis: Potential Therapeutic Approaches

16. Andrew H. Miller and Charles L. Raison. Nat Rev Immunol. Author manuscript; available in PMC 2017 Aug 3. Nat Rev Immunol. 2016 Jan; 16(1): 22–34. The role of inflammation in depression: from evolutionary imperative to modern treatment target

17. Udina M, et al. Interferon-induced depression in chronic hepatitis C: a systematic review and meta-analysis. J Clin Psychiatry. 2012;73:1128–1138.

18. Rodrigues FTS, de Souza MRM, Lima CNC, da Silva FER, Costa DVDS, Dos Santos CC, Miyajima F, de Sousa FCF, Vasconcelos SMM, Barichello T, Quevedo J, Maes M, de Lucena DF, Macedo D. J Psychiatr Res. 2018 Dec;107:57-67. Major depression model induced by repeated and intermittent lipopolysaccharide administration: Long-lasting behavioral, neuroimmune and neuroprogressive alterations.

19. Berk M, Williams LJ, Jacka FN, O’Neil A, Pasco JA, Moylan S, Allen NB, Stuart AL, Hayley AC, Byrne ML, Maes M. BMC Med. 2013 Sep 12;11:200. So depression is an inflammatory disease, but where does the inflammation come from?

20. Blomberg J, Gottfries CG, Elfaitouri A, Rizwan M, Rosén A. Front Immunol. 2018 Feb 15;9:229. Infection Elicited Autoimmunity and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An Explanatory Model.

21. Tremblay J, Hamet P. Metabolism. 2019 Nov;100S:153952. Environmental and genetic contributions to diabetes. 

22. Shariati A, Fallah F, Pormohammad A, Taghipour A, Safari H, Chirani AS, Sabour S, Alizadeh-Sani M, Azimi T. J Cell Physiol. 2019 Jun;234(6):8550-8569. The possible role of bacteria, viruses, and parasites in initiation and exacerbation of irritable bowel syndrome.

23. Sochocka M, Zwolińska K, Leszek J. The Infectious Etiology of Alzheimer’s Disease. Curr Neuropharmacol. 2017;15(7):996-1009.

24. Campbell LA, Rosenfeld ME. Arch Med Res. 2015 Jul;46(5):339-50. Infection and Atherosclerosis Development. 

25. Fulvia Ceccarelli, Nancy Agmon-Levin, and Carlo Perricone. J Immunol Res. 2017; 2017: 2789242. Genetic Factors of Autoimmune Diseases

This article was originally published as a guest editor post at foodpharmacy.se

By: Graeme Jones, clinical physiologist and CEO at Nordic Clinic Stockholm.

Published: 08/04/2020

COVID-19, the highly infectious novel coronavirus spreading throughout the world, is leaving a path of destruction in its wake and shutting down entire societies. As I write this on March 28, it’s currently responsible for over 30,000 deaths around the world and 18,000 deaths in the EU¹. Initially, age was considered the biggest factor based on data from Wuhan, China, where the virus started².

Due to its older population, Italy has been hit hard. Currently, more than 10,000 people have died from COVID-19 in Italy. Early data in Italy indicates that the average age of those infected with COVID-19 is 63 years old, and the average age of those who have died is 78.5 years old³.

Much of the early data focused on age as the predominant factor in poor COVID-19 outcomes. This is consistent with the general trend of decreasing viral immunity with age (our immune system becomes less effective and therefore risk of complications becomes worse as we age). But what has been very interesting to me, is that further data outlines that age isn’t the only important factor predicting death of COVID-19.

Data out of Italy indicates that 98.8% of those who died of COVID-19 had a pre-existing condition that contributed to their death. Furthermore, over 75% had 2 or more comorbidities³ (a comorbidity is one or more diseases or condition/s that exist with other conditions e.g. high blood pressure with COVID-19). This should be a massive wake-up call to everyone and governments in the realm of chronic disease prevention.  

Table: Most common comorbidities observed in COVID-19 positive deceased patients³

As you can see from the image, the top 3 comorbidities for death from COVID-19 are hypertension, ischemic heart disease, and diabetes. Conspicuously, chronic obstructive pulmonary disease (COPD), which in most cases is caused by chronic smoking, is 7^th. How can a progressive and chronic inflammatory lung disease be so far down the list? COVID-19 is a lower respiratory infection that becomes fatal most often due to respiratory failure. As we shall see, systemic inflammation seems ‒ somewhat surprisingly ‒ to play an even bigger part in COVID-19 mortality than COPD.

Metabolic health and COVID-19 outcomes

As we get older, several changes increase our risk and severity of viral infections. One in particular is a gradual increase in systemic inflammation often referred to as inflamm-aging⁴. Interestingly, changes in the gut and microbiome are considered important drivers of this chronic inflammation.

Obesity promotes a chronic inflammatory state similar to that seen with aging. Again, the microbiome is considered a primary driver of this effect⁵. Recent evidence indicates that the western lifestyle may be the cause of this inflammatory state by promoting an inflammatory microbiome⁶.  

As a result of chronic inflammation, our risk for chronic disease increases as we age. That’s why chronic diseases such as type 2 diabetes, hypertension, and cardiovascular disease are often referred to as the chronic disease of aging. However, age is not a prerequisite for chronic disease. It’s becoming more and more common for younger people to become afflicted with the chronic diseases of aging. 

As such, people with chronic metabolic diseases are at an increased risk of poor outcomes from COVID-19 infection, regardless of age. Thus, addressing specific aspects of the Western Lifestyle is important for reducing the risk of COVID-19 infection and improving outcomes. This includes:

• Consuming a diet high in vegetables and fiber
• Addressing circadian rhythms (our evolutionary preferred wake/sleep patterns)
• Being active/exercising
• Maintaining a healthy weight
• Prioritizing sleep
• Managing stress
• Limiting alcohol intake
• Not smoking

These are all areas that currently our healthcare system is terrible at giving advice on. I have seen thousands of patients at Nordic Clinic Stockholm and I can barely count on one hand patients that have reported to me that their doctor is providing them with any substantial advice in any of these areas.  

While age is a factor that you have no control over, lifestyle is not. Thus, a healthy lifestyle may be your biggest weapon against death from COVID-19 infection. Considering this information, I am now becoming very worried to see the impact of COVID-19 on the US, UK and even Sweden’s population. The US has extremely high rates of obesity and the UK and Sweden are not far behind. As it stands, although I am sure there will be some outliers, I believe we will continue to see the people most affected by this pandemic as having some sort of underlying chronic health condition.  

Functional medicine, the model we follow at Nordic Clinic, is not a model for acute care. Luckily, those that have COVID-19 and that are in acute trouble could not be under better care with our standard healthcare system in Sweden. But the same healthcare system is failing miserably at preventing chronic disease and needs to do better to test and educate the population for risk of chronic disease. Doctors are given close to zero training in nutrition, exercise, sleep and other lifestyle factors that undoubtedly are the cause of poor cardiometabolic health. At the heart of Functional Medicine we measure, track and advise patients on their currently chronic disease risk, preventing it before it has a chance to happen. 

Lifestyle and preventative health need to be taken more seriously

Initial reports out of both China and Italy indicate that COVID-19 will hit older populations hard. Unfortunately, in the EU, this gives young people a false sense of security. Looking at all the data, it’s clear that, while age is one important factor, established metabolic disease is another.

Therefore, it becomes increasingly important for people of all ages to maintain metabolic health. Hypertension, type 2 diabetes, and cardiovascular disease seem to be particularly harmful and predict poor outcomes from COVID-19 infection. Addressing lifestyle should be a first line of defense in the fight against COVID-19 infection and people and governments need to take preventative health more seriously. 

We need to utilize measurement tools and more sophisticated testing of lifestyle, and have doctors who are better equipped to understand that data and give evidence-based advice. It is out there, but Sweden continually refuses to embrace it, deciding to try and manage chronic disease once it has happened.  

Functional Medicine is a system that could fill this void and work alongside the current acute care system, and it is about time our politicians take this more seriously.  

References

1. https://www.statista.com/statistics/1093256/novel-coronavirus-2019ncov-deaths-worldwide-by-country/
2. https://www.worldometers.info/coronavirus/coronavirus-age-sex-demographics/
3. https://www.epicentro.iss.it/coronavirus/bollettino/Report-COVID-2019_20_marzo_eng.pdf
4. https://www.ncbi.nlm.nih.gov/pubmed/30046148
5. https://www.sciencedirect.com/science/article/pii/S1568163719302880
6. https://www.nature.com/articles/s41577-019-0156-1?fbclid=IwAR3jEVbq918MMVcGfT5pvJ71CJcLDCBfZg4acaL9tasYS1jCHACBIZcxlv8#citeas

By: Graeme Jones, clinical physiologist and CEO at Nordic Clinic Stockholm

Published: 03/04/2020

As the COVID-19 pandemic sweeps the world, doom and despair dominate the news around the clock. We fear for the health and livelihood of ourselves and our loved ones. In times like these it’s important that we maintain perspective.

Given the current situation I’d like to contemplate the pandemic from another point of view. Let me start by saying that chronic disease is THE leading cause of death and disability throughout the developed world. This is completely different to our grandparents and previous generations who primarily dealt with infectious disease and diseases of nutritional deficiency. Now as such, modern healthcare systems are well-equipped to address these acute conditions. 

With the arrival of better hygiene, antibiotics, and identification and manufacture of essential nutrients, we have these conditions mostly under control. Get a bacterial infection, take an antibiotic. Have a B12 deficiency, take a supplement. But now there’s a new threat to our health, and it’s growing. Surprisingly you might wonder, this threat is not COVID-19, but rather the possible implications that COVID-19 is having on our society. 

With the current COVID-19 situation and the huge economic and social impact being enforced on our populations, I dare ask myself this question:  although the political actions taken may save lives within the “at risk groups” and reduce burden on the healthcare systems, what could be the larger potential fallout from these stringent measures? I cannot help but recognize how all of this is causing so much stress, worry and anxiety.  I encounter mood and anxiety disorders in my everyday work of seeing clients, and I follow research on the topic closely, noting a jump in the prevalence of these conditions throughout populations world-wide. Mood and anxiety disorders are becoming increasingly common forms of chronic disease.  Furthermore, stress, mood and anxiety disorders predispose and associate with other forms of chronic disease. For example, there is a well-studied relationship between functional gastrointestinal disorders and mood disorders¹. Insomnia and depression are also linked², as are depression and chronic pain³.  

Chronic disease is nothing like acute infection or nutritional deficiency. While you can use the term “cure” to describe what happens when you treat acute infection effectively, chronic disease is more about management. This is not to say that chronic disease cannot be cured, just that it cannot be approached like acute infection/nutritional deficiency. In fact, some common chronic diseases, like type II diabetes can be cured and many can at least be effectively managed through lifestyle changes. 

Addressing chronic disease successfully requires a recipe that uses a “personalized overview” sort of approach, as we use in Functional Medicine. It needs a large dose of lifestyle intervention accompanied by a targeted medical and detective approach that addresses and understands underlying causes. But let’s make no mistake, the lifestyle portion is crucial, and stress plays a huge role in it all.

Stress and chronic disease: Predisposing factors, acute stressors, and perpetuating habits

A recently published paper put forth an interesting paradigm for Post-Traumatic Stress Disorder (PTSD)⁴. It’s such an elegant paradigm that it likely applies to how stress exacerbates and perpetuates most chronic disease. The infographic below details the model:

In this model, there are three categories of factors that promote susceptibility:

• Genetic predisposition ‒ genes that set the tone for your sensitivity to stress
• Cacostatic load ‒ the cumulative amount of stress your body is under
• Early environment ‒ early life experiences that set your stress “tone”. Things such as fetal stressors (smoking, premature birth), the environment you were raised in, socioeconomic status, and early life trauma

Traumatic stress refers to the triggering event that tips a person into chronic disease. In PTSD this may be combat, loss of a loved one, major financial loss, tragic accident, or major illness. But in a condition like irritable bowel syndrome (IBS), it may be an initial food poisoning leading to post-infectious IBS. The stress need not be psychological; anything that stresses the body will do.

The combination of susceptibility and a traumatic stressor can lead to a disruption of our circadian rhythm; our evolutionary preferred wake/sleep patterns. This is especially likely in those with genes that predispose to it. In PTSD this leads to alterations in glucocorticoid signaling (stress hormones, such as cortisol). In type 2 diabetes it may lead to improper glycemic (blood sugar) control.  In functional gut disorders, it could lead to alterations in bile output (which helps to break down fat), gut motility (which helps to protect against IBS), or pancreatic insufficiency (lack of enzymes to break down food).

This puts the patient at a pivotal point. If they correct the circadian disruption, symptoms are transient and the patient recovers. However, if the circadian disruption persists and becomes chronic, this traps the patient into a state of chronic disease. Since chronic disease tends to beget chronic disease, comorbidities accumulate.

Addressing excessive and cumulative stress

Most of the factors in this paradigm are constants. Stressful events are going to happen no matter how hard you try to control for them. At the top level, you have no control over your genes or your early life environment; those things are set in stone. You can, however, adjust your cacostatic load and work to prevent chronic circadian disruption after the triggering event.

Cacostatic load simply refers to the cumulative amount of stress your body is under, including disease states. Genetic susceptibility and early environmental stress regulate how your body responds to stress. They also play a role in the amount and types of stress you can deal with. Be that as it may, lifestyle is a big factor as well.

Many lifestyle factors regulate our sensitivity to stress as well as our capacity to deal with it, including:

• Sleep ‒ maintain a consistent schedule and good sleep hygiene
• Circadian rhythms ‒ pay attention to your light environment & feeding/fasting cycle
• Exercise ‒ get adequate moderate to vigorous physical activity every week (>150 minutes)
• Being active ‒ walk more, sit less
• Weight ‒ maintain a healthy weight
• Diet ‒ follow a nutrient dense, unprocessed diet with a high of variety of different foods
• Stress ‒ reduce stress exposure and/or manage stress using tools such as meditation and yoga

Building resilience by prioritising these behaviors lowers cacostatic load and increases the amount of stress you can experience before hitting the tipping point. It also ensures that the acute circadian disruption after a traumatic event is acute, and transient.

Take action – resilience is key

Many face – or have already faced – major personal or financial loss due to COVID-19. We return to the question at hand; may the soaring anxiety levels make more damage to our health than the pandemic itself? In my experience of working with stress-related illness, it may well be. Indeed, science provides robust support to the stress-disease hypothesis.

Stress is a major contributor to the chronic disease burden in the developed world. Whereas our ancestors were intermittently exposed to acute stressors, most of us are under chronic stress. Our cumulative exposure to stress can place a burden on us that is represented by cacostatic load. Other factors such as genetics and early life environment play a role in susceptibility, too.

Building a strong foundation of resilience is key to preventing stress from pushing yourself past the tipping point. It’s also critical to being able to bounce back when a strong enough triggering event knocks you down. Sleep well, keep a schedule, exercise, eat a healthy diet, manage your stress and remove the stressors you can. It could make the difference between being happy and healthy or sick and depressed. This is even more pertinent in the current times. 

References

1. https://www.ncbi.nlm.nih.gov/pubmed/28087404

2. https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-016-1075-3

3.https://www.sciencedirect.com/science/article/abs/pii/S0165032717308364?via%3Dihub

4. https://www.frontiersin.org/articles/10.3389/fpsyt.2019.01003/full?fbclid=IwAR3tY-fER9ItPOJ38xPtdcywHOJ6DlFL2fbWkxRAPGOiwODaI0gVlK8chuw