All about inflammation and anti-inflammatory lifestyle (Part 2)

anti-inflammatory strategies

In Part I we discussed how inflammation can cause a wide variety of serious medical conditions.  So, obviously, you should make every effort to keep inflammation at bay.  This article discusses anti-inflammatory strategies to improve your health and prevent chronic diseases.

One big problem with the way inflammation is being treated in traditional medicine today is that – as with many other conditions – the emphasis seems to be on managing symptoms with anti-inflammatory drugs, rather than eliminating the root cause (one could argue that this is a much more profitable approach for pharmaceutical companies in the long-run).  Anti-inflammatory drugs (also called non-steroidal anti-inflammatory drugs, or NSAIDs) reduce pain, fever and swelling by blocking proteins and enzymes naturally produced in response to tissue damage.

You probably know most of the brand-name NSAIDs – Aspirin, Advil, Aleve, Ibuprofen, Motrin, Naproxen, Celebrex, Voltaren – there are also a dozen or so generic variants, some of which can be bought over the counter and some require a prescription.  They are typically used for pain relief – from headaches to back pains to more serious and chronic conditions, such as arthritis.

But while they can definitely eliminate the discomfort and improve the quality of life, anti-inflammatory drugs could be a double-edged sword.

Not only it is now understood that NSAIDs can cause complications, such as heart attacks, strokes, worsening of asthma symptoms, stomach ulcers, intestinal bleeding and fluid build-up in kidneys which may lead to higher blood pressure – and the risks that are even higher when more than one NSAID is used at the same time, (to a point of such drugs carrying warning labels regarding these conditions) – the direct benefits that anti-inflammatory drugs promise are also questionable.  When you recall that inflammatory response also initiates tissue healing and elimination of pathogens – blocking such response could, essentially, help the pathogens proliferate and do more damage.  This, by the way, is not only the case with invading pathogens, but also with auto-immunity-type inflammatory reactions, such as osteoarthritis – in fact, anti-inflammatory drugs can accelerate osteoarthritis-related tissue-degeneration, by blocking the production of healing prostaglandins.

So what is the best way to reduce inflammation without anti-inflammatory drugs?  Naturally – by focusing on eliminating the root cause, as opposed to just masking the symptoms.

Systemic inflammation symptoms

Most people do not understand the link between their chronic condition and inflammation.  After all, systemic inflammation is not easy to identify because it doesn’t necessarily present visually apparent clues, as is the case with acute local inflammation).

Nevertheless, inflammation may be a prominent factor in obesity, general bloating, sluggishness, immune disorders, allergies, skin conditions, joint pain (ranging from temporary discomfort to full-blown osteoarthritis), digestive disorders (once again, ranging from a temporary stomach upset to irritable bowel syndrome), chronic headaches.  Really, the list is just too long – but a lot of times you may not even think of inflammation being a culprit.  Puffiness in the face and general skin problems? Difficulty losing what seems to be a layer of stubborn body fat (especially around the waist)?  Decreased focus and concentration?  Memory problems?  Constant fatigue?  Yes, you got it – all of these could be symptoms of systemic inflammation.  And while most people think of many of these problems as local issues and try to fight them locally, too – most of these efforts would be futile without addressing the real cause.

The role of free radicals and anti-inflammatory properties of antioxidants

Generally speaking, radicals (most often called “free radicals”) are extremely reactive atoms that have unpaired electrons. A free radical can react quickly with the closest stable molecule and “steal” its electron to balance itself out – meanwhile the attacked molecule can become a free radical by losing its electron and start a chain reaction cascade causing damage to the living cell.

There are many types of radicals, but those of most concern in biological systems are derived from oxygen, and known collectively as Reactive Oxygen Species (ROS) – the two unpaired electrons in separate orbitals in its outer shell make oxygen especially susceptible to radical formation.  Sequential reduction of molecular oxygen (sequential addition of electrons) or a jump of one of its electrons to a superior orbital creates a group of reactive oxygen species, such as superoxide anion, peroxide (hydrogen peroxide), hydroxyl radical or singlet oxygen.

ROS are formed as necessary intermediates in a variety of normal biochemical reactions – this is a constant – and necessary – process that you cannot avoid (ROS play crucial roles in activation of signaling pathways in cells which alter the intra- and extracellular metabolism).  Notably, a lot of free radicals are generated in mitochondria as a part of normal aerobic life, during the process of oxidative phosphorylation.  Your body normally produces natural anti-oxidants to counteract the damaging effect of such reactive oxygen species.

But when generated in excess or not appropriately controlled, radicals can wreak havoc on a broad range of macromolecules.   In particular, lipids, proteins and nucleic acids are important targets for oxidative attack.  Peroxidation of membrane lipids can have numerous effects, including increased membrane rigidity and altered permeability, decreased activity of membrane-bound enzymes, altered activity of membrane receptors.  When radicals directly attack membrane proteins they induce lipid-lipid, lipid-protein and protein-protein cross-linking, affecting membrane functions.  Generally speaking, such alteration of these molecules can enhance the mutagenesis process (the first step to cancer).

How free radicals relate to inflammation

So how is all this related to inflammation?  In a very direct way, it turns out!  Disregarding the effects of ionizing radiation (which is beyond the scope of this article), the two other important examples of cases when oxygen radicals are overproduced in cells are:

  • Over-recruitment of white blood cells (such as neutrophils), which specialize in producing oxygen radicals normally used in host defense to kill invading pathogens (this should sound familiar form our discussion on white blood cell’s involvement in inflammation in Part I). Chronic inflammation – which keeps your inflammatory responses on all the time – can do that;
  • In general, cells exposed to abnormal environments generate abundant and often damaging reactive oxygen species. Constant inflammation that does not subside can very well be classified as “abnormal” and, thus, become a major contributor;

In inflammatory response, leukocytes and mast cells are present in large amounts in the affected area, and, as a result of an enhanced uptake of oxygen, the production and release of ROS is also increased.

Moreover – inflammatory cells generate more soluble inflammatory mediators (cytokines, arachidonic acid, chemokines), which release more reactive species, which, through a cascade of different chemical reactions, play a role in further oxidative stress-induced inflammation. In other words, inflammation can trigger overproduction of free radicals, which further trigger more inflammation.  This inflammatory/oxidative environment leads to a perpetual cycle, which can harm healthy stromal cells and neighboring epithelial cells – and this, after a long period of time, may trigger carcinogenesis.

Antioxidants

Because generation of reactive oxygen species is a normal biological process, our bodies have evolved a host of natural defenses against free radicals.  These defenses involve either preventing reactive oxygen species from being formed or deactivating them before they cause substantial damage by way of chemical reactions that eventually donate missing electrons to radicals and thus stabilize them.  The group of molecules that inhibits oxidation of other molecules is collectively called “antioxidants”.

The function of natural antioxidant systems is not to remove oxidants entirely, but instead to keep them at an optimum level (remember that some level of oxidative activity is essential for normal cell functioning).  Quite a bit of such antioxidants are enzymatic and generated internally – examples include:

  • Superoxide Dismutase or SOD (which catalizes the conversion of extremely toxic superoxide into substantially less toxic hydrogen peroxide and oxygen and depends on a bound manganese, copper or zinc for its antioxidant activity),
  • Catalase (which degrades hydrogen peroxide to water and oxygen, and finishes the detoxification reaction started by SOD),
  • Glutathione peroxidase (a group of enzymes, the most abundant of which contain selenium, which also degrades hydrogen peroxide and reduces organic peroxides to alcohols, providing another route for eliminating toxic oxidants),
  • Others (ceruloplasmin, hemoxygenase and several other enzymes).

The non-enzymatic antioxidants are typically ingested with food – the most notable and particularly important are:

  • Vitamin E, with its most active form of alpha-tocopherol (lipid-soluble antioxidant with a vital role of protecting membranes from oxidative damage by trapping peroxy radicals in cellular membranes and triggering apoptosis of cancer cells);
  • Vitamin C or ascorbic acid (a water-soluble antioxidant that can reduce radicals from a variety of sources and appears to participate in recycling vitamin E radicals),
  • Beta-carotene (found to react with peroxyl, hydroxyl and superoxide radicals) and numerous other small molecules that function as antioxidants.
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While donating their electrons, antioxidants get oxidized themselves, but typically, your body’s natural reduction systems take care of that.  For instance, vitamin C, as mentioned above, helps convert vitamin E free radicals back to vitamin E.  A redox cycle involving glutathione reductase and the electron acceptor NADPH helps regenerate glutathione after it gets oxidized, etc.

Three are also minerals that have no antioxidant action themselves and are instead required for the activity of some antioxidant enzymes, such as selenium and zinc.

Glutathione (GSH) – a master anti-oxidant

Of many antioxidants that stand on guard for you, glutathione, the most important intracellular defense against damage by reactive oxygen species due to its chemical structure which makes it very reactive and provides an abundant target for radical attack, may very well be the most important – so much so that the ratio of GSH to GSSG (oxidized form of glutathione) is a major indicator of oxidative stress.  Glutathione is produced by all cells and is highly abundant in all cell compartments, but the vast majority of it is generated by the liver.

Not only GSH exhibits potent antioxidant effects itself (by detoxifying hydrogen peroxide and lipid peroxides, it is also a cofactor for several detoxifying enzymes, such as Glutathione peroxidase (GSH-Px) and transferase, has a role in converting vitamin C and E back to their active forms, protects cells against apoptosis by interacting with proapoptotic and antiapoptotic signaling pathways and regulates several transcription factors, such as AP-1, NF-κB, and Sp-1.

Anti-inflammatory foods, spices and other compounds

Remember your mother telling you to eat your veggies?  She was right!  The more colors – the better (different colors represent different antioxidants and phytonutrients that have different functions, the bigger the color variety – the better your exposure to them) – obviously we are not referring to artificial colors in some vegetable chips!  Remember, antioxidants and other beneficial compounds can reduce inflammation.

You already know from many other articles on this website that, generally speaking, when most of your energy comes from dietary fat as opposed to carbohydrates, your chances of reducing inflammation are much better.  When you do eat carbs – avoid simple sugars, anything made from grains or its derivatives and starches.  Stick to complex carbohydrates from fruits and vegetables with a low glycemic index such as apples, asparagus, broccoli, blackberries, blueberries, cabbage, cantaloupe, citrus fruits, leafy greens, pears, raspberries, spinach and strawberries.  For extreme cases, when you are battling some medical condition and need to be really diligent and strict about what you eat, consider tipping the scale towards some variation of ketosis.

There are also several herbs and spices that help reduce inflammation – such as chili peppers (containing capsaicin, a naturally occurring ingredient), rosemary (with its rosmarinic acid), ginger, natural vanilla, basil, bay leaves, cumin, coriander, dill, fennel, garlic, oregano, pepper, sage and thyme. Make it a habit to season your food with natural organic spices listed above – not only this improves taste, the health benefits are also much higher.  Turmeric has been praised for its anti-inflammatory properties for a long time – so much so that it serves as a very viable alternative to medication when it comes to reducing inflammation-based aches and pains – it is a dose-dependent result, however, so for best results you might need to consider concentrated turmeric supplements.  Incidentally, black pepper makes turmeric more bioavailable in your body, so combining the two (which is easy to do when seasoning food) makes a lot of sense.

Some of the less consumed, but still very effective ingredients include green tea extract, spirulina (an excellent source of a very wide range of nutrients) and willowbark.

Overabundance of anti-oxidants is not the best strategy.

So, we talked about oxidative stress – but did you know you can also subject your cells to anti-oxidative stress?   Overabundance of bioavailable antioxidant compounds may interfere with the immune system’s ability to neutralize pathogenic threats – in fact, anti-oxidative stress has been notably implicated as an underlying cause of allergies and asthma.

In addition, not all anti-oxidants are created equal.  Relatively strong reducing acids normally present in high amounts in plant-based diets – such as oxalic acid, phytic acid and tannins, (which can, otherwise, function as anti-oxidants) can have anti-nutrient effects by binding to dietary minerals such as iron and zinc in the gastrointestinal tract and preventing them from being absorbed.

Reducing Inflammation by straightening out dietary habits

What are dietary habits that lead to inflammation?  Here are a few examples:

  • High-carb diets. High carb diets contribute to loss of insulin sensitivity and, progressively, to type 2 diabetes. Patients with type 2 diabetes have higher levels of inflammation and this may contribute to a higher risk of cardiovascular disease and other complications.  Simple carbohydrates rev up inflammation by causing surges in blood sugar that promote a chemical reaction in cells called glycosylation, or the browning effect.  Clinical trials demonstrate that patients with type 2 diabetes on a low-carbohydrate diet exhibited reduced levels of inflammatory markers in blood, compared to patients on traditional low-fat diet, despite the fact that weight loss was similar in both groups.
  • Lack of natural foods. Overuse of artificial sweeteners, neglect of fermented foods, abundance of nutritionally-void over-processed meals that are typically full of preservatives, artificial colors and other chemicals – all of this wreaks havoc on your gut bacteria.  The gut houses the bulk of the human immune system – so compromising intestinal bacteria compromises your immune system and, as a result, inflammatory regulation;
  • Insufficient intake of Omega-3 and abundance of Omega-6 oils. Given almost a total domination of pseudo-healthy “cooking oils” – such as corn oil, sunflower oil, peanut oil, soybean oil, cottonseed oil – and their abundance in processed fast foods and packaged meals, the Omega-6 / Omega 3 ratio for most people consuming standard modern diets is heavily skewed towards the former – this, as we previously covered, creates a pro-inflammatory environment.  Poor omega-3 status means insufficient production of anti-inflammatory eicosanoids.
  • Eating deep-fried foods. Yes, this needs to be a separate bullet point – that is how important it is!  Not only the oil used for deep-frying in restaurants (and often – in homes) is pro-inflammatory to begin with, subjecting it to very high temperatures (which is what deep frying is all about) and acceleration of their peroxidation pushes the level of free radicals through the roof – and promotes further peroxidation of lipids in your body, resulting in increased inflammation.  Deep-fried food is the worst kind of food you can eat – so stay away from it at all cost.

Other factors that influence inflammation

Lack of sleep.

As our lives get busier and busier and more and more distractions are introduced, poor sleep becomes a chronic problem in developed nations. We go to bed too late, wake up too early, use too many electronics at night that disrupt the quality of our sleep with their blue screens that disrupt our circadian rhythms, etc.  Such decrease in the amount and/or quality of sleep has its consequences – and among other things, poor sleep is linked to elevated inflammatory markers – this was after only a few days of disrupted sleep (where participants were losing 2 to 4 hours of their normal sleep time).  Imagine the effects as they mount over time for those who constantly get at least partially sleep-deprived!

“Chronic cardio” exercise. 

Here are some interesting facts about exercise.  Acute exhaustive exercise increases inflammatory markers (CRP, IL-6, TNF-α) and oxidative stress.  But skipping exercise altogether is, of course, not the right solution either.  Absence of exercise (or, generally, lack of activity and movement and leading a sedentary lifestyle is strongly linked to systemic, low-grade inflammation.

As a matter of fact, some inflammation is actually necessary and it is often what drives your tangible results – whether it is hypertrophy, endurance or strength – the inflammatory response to the stress makes your body stronger and rebuilds its tissues to deal with future demands.  Effective exercise is an acute stressor that initiates a temporary, but powerful inflammatory response.  Moreover, regular training with proper recovery may provide necessary changes to adapt to exercise and to trigger mechanisms against inflammation that will occur after muscle activity.

And it’s not just muscles that benefit from proper exercise – it also trains your arterial walls, causing the endothelium to produce more nitric oxide (which inhibits LDL oxidation) and significantly increase the expression of anti-inflammatory and anti-oxidant proteins.

The effects of occasional acute exercise are, however, extremely different from those of chronic training.  Studies show that markers of inflammation are actually quite stable in the days after a single session of moderate-intensity aerobic exercise in apparently healthy men of at least average fitness – but the picture changes dramatically if these exercise sessions turn into constant exhaustive efforts without sufficient recovery.  It is all about finding that balance – too much exercise – just as too little of it – become the cause for systemic inflammation.,

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Whether you look at studies that refer to extreme examples (such as those that confirm acute inflammatory response in muscle tissue and marked increases in plasma levels of many markers of inflammation following spartathlons – which is 246 km of continuous running!) – or those that refer to only a moderate overtraining (such as two weeks of moderate, but daily exercise leading to significant increases in CRP and TNF-α with a significant decrease below baseline in the same markers of inflammation during subsequent recovery – the common theme is the same: exercise-induced inflammation does not subside and turns into chronic systemic inflammation unless you allow sufficient time for recovery.  In contrast to the reduction of chronic inflammation by regular, moderate exercise (which results in release of epinephrine, cortisol, growth hormone, prolactin and other factors that have immunomodulatory effects), prolonged, high intensity training results in increased systemic inflammation and elevated risk of infection.  Subsequent to this type of exercise, athletes exhibit a transient exercise-induced immunodepression.

Inflammation, of course, is not just a direct result of just “cardio”-type workouts.  Any intense workout that is too long and too frequent has a potential to increase inflammation. But it’s hard to overdo resistance exercise as you would be under load (albeit potentially a quite heavy load) for only a very short time – and then, if you follow any meaningful program, will take quite a bit of time to recover before going at it again.  By contrast, regularly training for marathons and other ultra-endurance events requires A LOT of time.  Moreover, with heavy-weight resistance exercise (let’s call it weight lifting), if you haven’t recovered sufficiently – you just won’t make the lift.  In fact, you probably won’t even attempt a very heavy lift if something feels off (at least this is the right thing to do).  Contrast that to endurance workouts – and the fact that many people force themselves through them because it is lower intensity and relatively easier to just will-power through.  When you do – and you still will probably be able to, despite all the little signs your body would be giving you – you will make the problem even worse.

Hopefully, you understand now why doing these daily long runs and other chronic cardio exercise without proper recovery may not be as healthy as you might have been lead to believe.

So build your training sessions around lots of acutely stressful resistance exercise with plenty of recovery time and lots of low-intensity slow-moving (like walking daily and generally being active and non-sedentary) and be cautious with long and frequent cardio-type workouts (nothing wrong with properly structured aerobic activity, though).  When you exercise in the right amount, the risk of systemic inflammation will actually get lower.

Tobacco and alcohol

It’s hard to find anyone these days who would deny that smoking is bad for your health.  Most of the time detrimental effects of smoking are discussed in the context of elevated lung cancer risk.  But it’s not only just those extreme cases you have to fear – studies show that inhaling hot tobacco smoke acutely increases inflammation.  Inflammation of endothelium and inflammatory stress on atherosclerotic plaque increases the risk of cardiovascular disease and stroke – and the cumulative effect of very long-term smoking may be such that this chronic inflammation never truly subsides even after you quit.  So the best strategy is – don’t start.  Or, if you are already a smoker, quit as soon as possible.

Similarly, while many of you enjoy an occasional glass of wine (and, perhaps, something stronger) – remember that, in the long run, alcohol is still a potent toxin that increases inflammation (especially intestinal inflammation) and generally disrupts cellular machinery.  So, be very mindful of the amounts you consume and – although it is probably unrealistic to expect that alcohol will be fully eliminated from your social lives – do not think for a minute that it is somehow good for your heart or some other nonsense.  It is a calculated risk – and nothing more.

Leaky gut as the source of low-grade  systemic inflammation

Your intestinal walls are designed to only let through specific small molecules important for your metabolism and restrict access to and further purge everything else. When the tight junctions in the gut, which control what passes through the lining of the small intestine, don’t work properly, other substances leak into the bloodstream.  Undigested or not fully digested proteins and fats, bacteria and waste showing up in your bloodstream trigger auto-immune reaction, as your killer cells attack those invaders and, along the way, also mistakenly attack healthy cells that contain molecules similar to those your immune system marks as harmful – causing systemic inflammation as a result.

Leaky gut is hard to diagnose, but a few tell-tale signs may include chronic fatigue, food allergies, seasonal allergies, joint pain, arthritis, skin rashes, weak immune system and even more severe conditions, such as irritable bowel syndrome, Crohn’s desease, Celiac, diabetes, lupus and several neurological conditions.   When you are talking systemic inflammation – what part(s) of the body this systemic inflammation may ultimately affect the most is really a wild guess.

Once again, with leaky gut there is a bit of feedback loop and a vicious circle – inflammation of intestinal lining increases its permeability, which leads to leaky gut, which leads to more inflammation throughout the body.  So, what triggers this cycle and causes leaky gut?  Pretty much anything that we discussed that can lead to inflammation – but, specifically, certain drugs (including, ironically, anti-inflammatory drugs), alcohol, diets that contain too much pro-inflammatory Omega-6 fats and insufficient amount of protective and anti-inflammatory Omega-3 fats, diets that contain many artificial overly processed ingredients – essentially, any diets that put undue stress on digestion and modify intestinal flora (yes, the change in bacterial composition in your gut matters, because beneficial bacteria and the products of their metabolism protect intestinal lining, while harmful bacteria damage it).  Specifically, we should note such anti-nutrients as gluten and phytates.  Gluten is believed to cause direct damage to intestinal lining through zonulin production.  Zonulin is a protein that modulates intercellular tight junctions and trafficking macromolecules.  One of the group of proteins in gluten (yes, it is actually a group of proteins, not a single protein), gliadin, has been shown in studies to activate zonulin signalling and, thus, induce intestinal permeability (the other major driver for zonulin release is bacterial exposure).  This sensitivity to gluten is irrespective of whether we are talking Celiac disease (pretty much the only officially recognized gluten sensitivity in traditional medicine) or not.  And, as we discussed in the past even non-Celiac gluten sensitivity may cause auto-immune disorders.

Solution?  Stop eating grains!  Especially considering that the second anti-nutrient abundant in them is phytic acid – which not only robs your body of important minerals, but actually leads to inflammation.

Conclusion

We have surely covered a lot – so here is a brief summary if you want to reduce systemic inflammation and get much healthier as a result:

  • Your number one goal is to reduce the source of inflammation, instead of increasing anti-inflammatory treatments. Anti-inflammatory medication may have side effects and other natural measures may only be partially effective if the root of the problem is not eliminated;
  • Inflammation is, essentially, your body’s way of letting you know that something is wrong, so don’t try to silence its voice by consuming inordinate amounts of anti-inflammatory compounds – instead, listen to it and try to correct the problem.  Of course, eating anti-inflammatory foods and eliminating inflammation-promoting habits remains a prudent tactic in a world where you cannot fully control your exposure to what may potentially cause problems (without even knowing or understanding the effects, you may be inhaling some toxic compounds by sitting next to a colleague who uses synthetic perfumes full of volatile compounds, you may move into a house or a building that has been recently renovated and where the materials are off-gassing a high amount of toxic chemicals, or you may be bombarded by high-frequency electro-magnetic fields from all corners of the world that becomes more and more “connected”) – but this should only be done in addition to reducing your exposure to the real causes of inflammation;
  • Following general healthy living guidelines (most of which you will find on this website) – such as sleeping enough, eating proper foods while eliminating common offending foods and cooking methods, decreasing body fat and exercising properly is – as usual – the very best way to reduce excessive inflammation and improve your quality of life;