Inflammation Near and Far, East and West

Two related questions. 

Q1. If, thanks to our terrible diets and lifestyles, chronic inflammation is rife (and the public health stats make it very clear that it is), why do some folk develop cardiovascular disease while others get arthritis, and others again present with asthma, osteoporosis, a neurodegenerative disease such Alzheimer’s or an inflammatory skin disorder such as psoriasis?

Q2. If inflammation is occurring in one site and producing inflammatory mediators at that site, aka the inflammatory cycle (1), are the damaging effects local or are they going to show up elsewhere? Or everywhere?

The idea that these questions are inter-related is supported by the experience of clinicians who know very well that when they see a patient with one inflammatory disorder, investigation will often show that other inflammatory diseases are also present at a lesser and often pre-clinical level. Elderly patients with signs of atheroma in one or more coronary arteries usually also have essential hypertension, sub-optimal bone mineral density, reduced lung function, creaky joints, signs of reduced cognitive function, thinned skin … and because we consistently see these changes in our elderly, we have misinterpreted them as intrinsic signs of ageing. 

But they are, in most cases, something else. They are signs of chronic inflammation, due in large part to chronic intoxication. The intoxication is largely due to a diet that is calorie-dense and nutrient-light, depleted in anti-inflammatory nutrients, and chock-full of pro-inflammatory compounds.

The organ or site where the chronic inflammation first surfaces with clinical symptoms may be affected by genetic factors, by specific nutritional factors (such as functional deficiency of a nutrient or group of nutrients), or by occupational issues; for example, the runners who develop arthritis in knee and ankle joints. But that is just the start.

There is good evidence that the presence of one inflammatory disease can cause activation of another apparently unrelated disease, leading to multiple disorders via activation of an inflammatory response that accelerates the destruction of healthy tissue and drives disease progression, both locally and remotely.

So, for example, periodontal disease produces significant amounts of pro-inflammatory mediators in the oral cavity. Some of these are absorbed locally, while the rest is swallowed in the saliva and absorbed in the small bowel before entering the blood stream. This helps to explain why periodontal disease is associated with an increased risk not only of local pathology such as oral cancer (2) but also disease in remote sites such as heart disease, hypertension, pancreatic and kidney cancer, and various leukaemias (3).

Those red blood spots in the bathroom sink are a red flag.

Excess adipose tissue is also pro-inflammatory. In fact, obesity is now viewed as a state of systemic, chronic low-grade inflammation (4). Both the adipocytes and the macrophages that invade large fat depots produce a range of potentially harmful pro-inflammatory compounds (or adipocytokines) including PAI-1, tumor necrosis factor-α (TNF-α) and visfatin. 

There is evidence that this inflammation is reduced or inhibited by a diet rich in anti-inflammatory nutrients such as omega 3’s (5), the fat-soluble micronutrients vitamin E (6) and lycopene (7), the carotenoids in general (8) and various polyphenols (9). 

Unfortunately, the very same diet of ultra-processed and calorie-dense foods which makes so many of us fat, is depleted in omega 3’s, vitamins, carotenoids and polyphenols …

The above helps to explain why overweight and obesity are linked to a higher risk of diabetes, heart disease, hypertension, strokes and cancer of the breast, esophagus, kidney, pancreas, endometrium, colon and rectum.

This is a fairly systemic increase in risk, but there are regional or local factors too. Some fat deposits are more dangerous than others, and this may be due to their location. Sub-cutaneous and fat deposited around the hips and bottom) is less likely to be associated with the above problems than is intra-abdominal or visceral fat. This is because visceral fat is more likely to be invaded by macrophages (10, 11); the macrophages that invade visceral fat are more aggressively pro-inflammatory than those in sub-cutaneous fat (12); and because abdominal fat is adjacent to the abdominal organs, so any pro-inflammatory compounds leaking out from visceral fat will achieve higher concentrations in the abdominal organs than the same compounds produced by fat around the hips. This helps to explain why exercise, which is the best way of reducing intra-abdominal fat, is both cardio- and chemo-protective.

When it comes to chronic inflammation in the large bowel we have to consider another key factor, namely the overall balance of the microbiome. The ultra-processed diet is depleted in prebiotic fibers, and this predisposes to a microbiota which is predominantly gram negative. 

Increased amounts of lipopolysaccharide (LPS) in the large bowel and the concomitant reduction in butyrate production inevitably create excessive and chronic inflammation locally. The subsequent leaching out of these inflammatory mediators into the blood stream, and the damage to tight junctions in the gut which constitute ‘leaky gut’, then create inflammation elsewhere. This is probably how inflammatory bowel disease raises the risk of diseases in many other tissues (13).

There are plenty of good reasons, therefore, for taking a prebiotic blend, which switches the balance of the microbiota back to gram positive. In this way you lower LPS levels in the gut, boost butyrate production and thus reduce inflammation.

How does one know who will benefit from this approach, without undertaking expensive fecal genetic analysis? Chronic constipation is a clue, as are dietary records showing significant consumption of ultra-processed foods. But there may be subtler clues.

In patients with signs of chronic inflammation in tissues other than the gut, the combination of omega 3/ polyphenols will generally suffice to alleviate pain and stiffness, and – often – to stabilize the health condition. But if the microbiota are mostly Gram negative and pro-inflammatory, I frequently find that omega 3/polyphenol combination is insufficient to reduce pain and stiffness in the hips, upper thighs and pelvic girdle. In such cases the addition of ZinoBiotic is usually enough to remove the symptoms, and I believe this is because reducing inflammatory stress in the large bowel reduces local levels of inflammatory mediators.

This probably also affects the physically adjacent omentum, a complex and atypical immune organ that is involved in differentiating between self and non-self in the gut and abdomen. The omentum has a tendency to collect metastasizing cancer cells and support tumour growth (14), but at this time it is not known if this is inevitably the case or whether this is only true in modern, malnourished and pro-inflammatory subjects. I suspect that if the diet contains sufficient prebiotics and the microbiota is therefore producing high levels of butyrate, which passes into the omentum via the mesenteric circulation and by local diffusion, the cancer-enabling effects of the modern omentum might diminish or even disappear.

This is merely a working hypothesis at the moment, which I hope to be able to test in 2020.

In the meantime, consider increasing your intake of anti-inflammatory and antioxidant supplements. Consider also a stress reduction technique. Chronic stress increases serum cortisol, and this increases the tendency to form and store visceral fat. Switching between physical exercise and meditation (the old Oriental way), makes a lot of sense.

 

REFERENCES:

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3. Michaud DS, Liu Y, Meyer M, Giovannucci E, Joshipura K. Periodontal disease, tooth loss, and cancer risk in male health professionals: a prospective cohort study. Lancet Oncol. 2008 Jun;9(6):550-8.

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