Dr Dingle's Blog / inflammation
If you have been to one of my talks you would have heard me emphasize the importance of inflammation and the need to lower your body's chronic inflammation levels. Of course one of the major sources of ongoing chronic inflammation is the gut.
Inflammation is literally the body “on fire” and is a primary immune mechanism response of the body to a range of noxious stimuli. This can include infectious agents, such as bacteria or virus, oxidation or acidosis, damaged or diseased tissues.
The main function of inflammation is a short-term response to resolve infection and to repair damage in order to achieve homeostasis (balance) in the body. The ideal inflammatory response is therefore rapid and destructive, yet specific and very limited. This is the reddening and swelling you see around any infected or injured area. Most of us are familiar with redness, heat, swelling, and pain associated with inflammation. These symptoms are created by the activity of immune cells working to break down injured and dying tissues so that new, healthy ones can replace them.
Unfortunately, we have created a situation in which we now suffer from chronic low-level inflammation over decades of our lives as a result of our unhealthy and unbalanced lifestyles and diet. Chronic inflammation is being shown to be involved in the onset and the development of most, if not all, chronic illnesses that are currently at epidemic proportions in our society. These include atherosclerosis (damaged and blocked arteries), heart disease, stroke, obesity, neurodegenerative diseases, depression, Alzheimer’s, Parkinson’s disease, thyroid disorders, diabetes, asthma, autism, arthritis, celiac disease, eczema, psoriasis, multiple sclerosis, lupus, migraines, periodontal disease, sleep apnea, chronic kidney failure, cancer and ageing. This is a long list, yet these are only the most common conditions.
Even though chronic inflammation in the body is hard to detect, there are some common symptoms for which we should be on the lookout. These include the following:
Chronic pain in the joints and/or muscles
Allergies or asthma
Elevated blood pressure
Fluctuations in blood sugar levels
Gut issues (constipation or diarrhoea)
Aches, pain and sorenessThe inflammatory process is driven by the immune system. In order to reduce the incidence of disease, you must reduce inflammation, and to reduce inflammation you must identify and eliminate immune system trigger(s). The typical approach of allopathic medicine is to treat the symptoms of the disease itself, or the immune system (with immune-suppressive drugs) or inflammation (with anti-inflammatory drugs) directly without addressing the underlying cause of the disease. Sustainable health, on the other hand, looks at identifying and eliminating the sources of the inflammation to address the situation at its cause.
 Shelton and Miller 2010.
 Schwarzenberg and Sinaiko 2006.
 Taubes 2002; Ridker et al. 1997, 2000.
Previously I have written on the emulsifiers so I hope you have made some changes. The sulfites and other preservatives are considered food additives intended to limit bacterial contamination and are generally regarded as safe. However, as expected, bactericidal chemicals have been shown to damage beneficial bacteria in the human gut. Sodium bisulfite and sodium sulfite have been shown to have negative effects on our beneficial gut microbiota including Lactobacillus species after two hours of exposure at concentrations of sulfites between 250–500 ppm, concentrations typically found in foods.Sulfites are added to beer, wine, juices, dried fruit, processed fish, seafood, meats, and some canned goods and are intended primarily for controlling microbial growth, preventing browning and food spoilage. The sulfite concentration in red and white wine is around 70 mg/L and 122 mg/L respectively. This means that drinking about two glasses of wine (450 mL) a day equates to an intake of 75% to 130% of ADI for a 60-kg person. A glass or two of wine may have a benefit on the gut microbiome but the preservative in it doesn’t. Combined with typical additional intake of sulfites common in a Western diet, the average total dietary exposure to sulfites could come to a total of 294% of ADI for adults, well over the amount generally regarded as safe and a level likely to do harm to the gut microbiota.
 Irwin et al., 2017.
 Leclercq et al., 2009.
Until very recently little research has been done on the impact of food additives on the gut microbiome, despite their widespread use. Food additives are substances intentionally added during production, processing, packaging, transportation, or storage of commercial food products. However, many food additives including emulsifiers, flavor enhancers, non-caloric artificial sweeteners, organic solvents, gluten and nanoparticles are increasingly used in food processing and being shown to negatively impact microbiota composition.
Emulsifiers, a ubiquitous component of processed foods, and often considered inert have been shown to adversely affect the composition of the gut microbiota and lead to low-grade inflammation. In the intestines a multilayered mucus structure covers the intestinal surface allowing the vast majority of gut bacteria to be kept at a safe distance from gut cells that line the intestine. It seems that emulsifiers, which have detergent-like molecules dissolve and damage the mucous membrane leading to bacterial and toxin movement across gut wall.
In experiments the commonly used food additives, carrageenan (407) and carboxymethylcellulose (466) (CMC) are used to develop intestinal inflammation in animal models. Animal and human studies consistently report that carrageenan and CMC induce cell changes that are typical of inflammatory bowel disease while altering the microbiome, disrupting the intestinal lining and stimulating inflammation. Carrageenan is commonly used and has substantially increased over the last 50 years as a thickening and emulsifying food additive to improve the texture of commercial food products. It is found in milk alternatives such as almond and soy milk, processed meats, and soy-based products, dairy products such as chocolate milk, ice cream, cottage cheese, sour cream, and yogurt, mayonnaise and infant formula.
Two recently studied synthetic dietary emulsifiers polysorbate 80 (P80) and carboxymethylcellulose (CMC) promote inflammatory gut disorders and act directly our microbiome to increase inflammation. As a result the studies suggest that broad use of emulsifying agents might be contributing to increased incidence of obesity, metabolic syndrome and other chronic inflammatory diseases. To support this transferring feces from emulsifier-treated mice to healthy mice resulted in similar host and microbial alterations observed in mice directly treated with emulsifiers including tumor development and low-grade gut inflammation. Carboxymethylcellulose use is widespread throughout the food industry in products typically consumed by children including candy, chewing gum, “snack foods,” ketchup, and various baked goods, and currently, there are no quantitative restrictions on its use nor does its addition to food require to be declared in most countries.
 Lerner and Matthias, 2015.
 Chassaing et al., 2015.
 Johansson et al., 2008.
 Roberts et al., 2010.
 Martino et al., 2017.
 Tobacman et al., 200; Borthakur et al., 2007.
 Borthakur et al., 2007.
 Chassaing et al., 2017.
 Viennois et al., 2017.
 Swidsinski et al., 2009.
Many studies have been done on psychosocial factors and their impact on our health and even how long we live. More recently some of these have been able to show that having a sense of purpose can have many health benefits from lowering stress to reducing the risk of cardiovascular disease cancer and even living longer and it doesn’t matter how old you are. The benefits of perceiving and living a life directed toward a broader purpose are widespread and feeling that you have a sense of purpose in life may help you live longer, no matter what your age.
At a biological level having a sense of purpose has been shown to be associated with more positive body biochemistry and lower cortisol (stress) levels and lower levels of proinflammatory cytokines 1, the chemicals linked to cancer, heart attacks and chronic disease which represents one possible mechanism through which purpose in life influences mortality.
Having a purpose in life provides individuals with a sense of direction and goals for the future, as well as a marker of flourishing and a life well-lived. A strong sense of purpose buffers us from the storms of life. It like the roots of a tree, keeping us steady and grounded even in stormy weather. It provides us with a greater sense of controlling our direction in life, are more motivated and may even feel inspired. However, our sense of purpose is not to make money it has to be directed at something greater than yourself.
In research among teens and young adults having a sense of purpose enabled them to look beyond themselves to appreciate their role in the world and to build the psychological resilience necessary to overcome adversity. There is evidence that focusing on personally meaningful and valued goals can buffer the negative effects of stress by allowing individuals to reinforce a sense of who they are and that creating opportunities for individuals to cultivate a sense of purpose is important as we move forward as a society2.
Having a high sense of purpose in life has also been associated with lower risk of heart disease and stroke. In a review of 10 relevant studies with the data of more than 137,000 people they defined purpose in life as a sense of meaning and direction, and a feeling that life is worth living. Previous research has linked purpose to psychological health and well-being and this study found that a high sense of purpose is associated with a 23 percent reduction in death from all causes and a 19 percent reduced risk of heart attack, stroke, or the need for coronary artery bypass surgery or a cardiac stenting procedure. This is better than any drug and has multiple other benefits.
Previous studies have suggested that finding a purpose in life lowers risk of mortality above and beyond other factors that are known to predict longevity. Purposeful adults tend to outlive their peers and experience a diminished risk for both cognitive decline and disability in older adulthood. Moreover, having a purpose in life appears to lead to unique health benefits relative to other aspects of psychological well-being, such as having positive relations with others. In this study of 749 people with an average age of 60 found that the participants’ sense of purpose was positively associated with multiple positive health qualities including vigorous and moderate activity, vegetable intake, flossing, and sleep quality 3.
In another study of 6985 adults between the ages of 51 to 61 and a follow up for 14 years life purpose was significantly associated with all-cause mortality. Those with the strongest sense of purpose almost 2 and a half times more likely to be alive comparing those in the lowest life purpose category. Particularly compelling was the reduction in deaths from heart, circulatory, and blood conditions. Purpose had similar benefits for adults regardless of retirement status, a known mortality risk factor. And the longevity benefits of purpose in life held even after other indicators of psychological well-being, such as positive relations and positive emotions, were taken into account. These findings suggest that there's something unique about finding a purpose that seems to be leading to greater longevity 4.
These findings point to the fact that finding a direction for life, and setting overarching goals for what you want to achieve can help you actually live longer, regardless of when you find your purpose. So the earlier someone comes to a direction for life, the earlier these protective effects may be able to occur.
So what is your sense of purpose?
Write it down
1 Ryff CD, Singer BH, Dienberg Love G. Positive health: connecting well-being with biology. Philos Trans R Soc Lond B Biol Sci. 2004;359(1449):1383-1394.
2 A. L. Burrow, P. L. Hill. Derailed by Diversity? Purpose Buffers the Relationship Between Ethnic Composition on Trains and Passenger Negative Mood. Personality and Social Psychology Bulletin, 2013; DOI: 10.1177/0146167213499377
4 . P. L. Hill, N. A. Turiano. Purpose in Life as a Predictor of Mortality Across Adulthood. Psychological Science, 2014; DOI: 10.1177/0956797614531799
Diet has a profound impact on gut microbiota composition and function including the role of food additives.
The study found that TiO2 could alter the release of bacterial metabolites in the gut and affect the distribution of the commensal bacteria. They also found reduced expression of the colonic mucin 2 gene, a key component of the intestinal mucus layer, and increased expression of the beta defensin gene, indicating that TiO2 significantly impacts gut homeostasis. These changes were associated with gut inflammation and an increase in the rick of colon cancer.
These findings collectively show that TiO2 is not inert, but rather impairs gut homeostasis which may in turn prime the host for disease development.
After initial breakdown by chewing, food is churned by the smooth muscles of the stomach and is broken down by hyrdochlooric acid and stomach juices (enzymes). The pH of the stomach is highly acidic, around 1.5 (1.0-2.5) due to the hydrochloric acid which helps to kill harmful microorganisms, denature protein for digestion, and help create favorable conditions for the enzymes in the stomach juices such as pepsinogen (Adbi. 1976, Martinsen et al 2005). Not to mention sending messages along the GI tract that everything is working well in the stomach. If the pH is too high, say 3 or 4 (more alkaline) then the system does not work and you end up with digestive and health complications.
The small intestine is more alkaline as the acid contents from the stomach are neutralised so that digestion and adsorption of carbohydrates, proteins and fats can occur. As the mixed juices (chime) from the stomach moves into the small intestine, the pancreas secretes sodium bi carbonate and the gallbladder releases bile which is produced in the liver, to make it slightly alkali to a pH of 7 to 8. Bile salts play an important role in the balance of the gut microbiota and like the pH in the stomach are important in controlling disease microorganisms entry into our system.
Further breakdown of protein and fat takes place, and absorption of nutrients through the use of enzymes which break down complex molecules into simpler ones. However, all enzymes need certain conditions, including pH to work. At pH's that are not optimum, the enzyme becomes less efficient until it cannot work at all. In the small intestine, the enzymes that "work" there need an alkaline pH in order to have optimum working conditions. Inadequate acid neutralization in the small intestine likely interferes with nutrient absorption by diminishing further digestive enzyme activity (Borowitz et al 2015).
The more alkaline pH also favours the non-acid loving bifidobactria which produce short chain fatty acids (SCFA) such as acetic, propionic, and butyric acid, and hydrogen ions (Vernia et al 1988) which lower the pH of the food as it moves through to make it more acid, again for the more acid loving bacteria including lactobacilis species further down the large intestine. The large intestine absorbs water and salts, and stores the leftover material ready for excretion out of the anus is a little more acidic and favours the acidopholus species. The pH of the large intestine might go as low as 3.
The pH of the gut, right from the mouth to the anus is incredible important in determining the type of gut microbiota, gut health and your own health. In the stomach if it is not acid enough (no not too much acid) it sets of a chain of events that favours the wrong type of microbiota including helicobacteror and candida species known for causing stomach ulcers and other gut health problems as well as an overgrowth of lactobacillus which should not be there and lead to Stomach Bacterial Overgrowth (SBO). So optimal functioning of the gut relies on the optimal pH for that part of the GI tract. Even in the mouth if it is too acidic it favours lactobacteria, acid loving bacteria, which in the large intestine are really beneficial, but in the mouth contribute to tooth decay and periodontal disease. Similarly, if the pH in the small intestine is out of balance it contributes to an overgrowth of lactobacillus and a condition called Small Intestinal Bacterial Overgrowth (SIBO). It all comes down to the pH and getting it right from the start.
Treatments for obesity have been shown to reduce pain secondary to weight loss. Intestinal microbiota has been shown to influence obesity and pain sensitivity.
Physiological pain plays a life-essential protective role, while acute or chronic pathological pain indicates a medical problem that needs treatment and imposes a medical challenge. Neurotransmitters, immune cells, and hormones have been demonstrated to contribute in pathogenesis of chronic pain.
Pain threshold is influenced by several factors, including obesity, which alters adipose tissue metabolic and endocrine functions leading to alterations in systemic physiology including an increased release of fatty acids, hormones, and proinflammatory molecules that contribute to obesity associated complications. Studies have demonstrated that obese humans and rats are more sensitive to pain stimuli than normal weighted ones.
Previous studies have demonstrated a relationship between intestinal microbiota and diseases including pain disorders with probiotics having a positive effect.
In this study the mice taking probiotics had a significantly lower sensitivity to mechanical stimulation compared to their corresponding control. The results of this study suggest a protective effect of probiotics on nociception circuits, which propose a direct result of the weight reduction or an indirect result of anti-inflammatory properties of the probiotics.
Potential Nociceptive Regulatory Effect of Probiotic Lactobacillus rhamnosus PB01 (DSM 14870) on Mechanical Sensitivity in Diet-Induced Obesity Model
The intestinal microbiome is a plastic ecosystem that is shaped by environmental and genetic factors, interacting with virtually all of our organs, tissues and cells. One of the most important factors in regulating and controlling our microbiome is the pH or acid level.
While often mentioned in terms of the stomach the pH has a controlling role to play in the health of the whole GI tract from the mouth to the anus and changes in the “normal” pH anywhere in the gut can have large implications on the rest of the GI tract. The pH scale goes from 1 being very acidic to 14 being very alkaline. The level in our blood and tissues should be constantly around 7.36, neutral and the level in our GI trace varies from 1 to 8. We cover this a lot more in our book “Overcoming Illness” which focuses on the role of inflammation, oxidation and acidosis in illness.
After initial breakdown by chewing, food is churned by the smooth muscles of the stomach and is broken down by hydrochloric acid and stomach juices (enzymes). The pH of the stomach is highly acidic, around 1.5 (1.0-2.5) due to the hydrochloric acid which helps to kill harmful microorganisms, denature protein for digestion, and help create favorable conditions for the enzymes in the stomach juices such as pepsinogen. Not to mention sending messages along the GI tract that everything is working well in the stomach. If the pH is too high, say 3 or 4 (more alkaline) then the system does not work and you end up with digestive and health complications. For example, premature infants have less acidic stomachs (pH more than 4) and as a result are susceptible to increased gut infections. Similarly, the elderly show relatively low stomach acidity and a large number of people, more than 30%, over the age of 60 have very little or no Hydrochloric Acid in their stomachs.
Similarly, in gastric bypass weight loss surgery, roughly 60 percent of the stomach is removed. A consequence of this procedure is an increase in gastric pH levels that range from 5.7 to 6.8 (not 1.5) to making it more alkaline and as a result are more likely to experience microbial overgrowth. We see similar patterns in other clinical cases such as acid reflux in which treatment involves the use of proton-pump inhibitors and celiac disease where delayed gastric emptying is associated with reduced acidity and increased disease.
Unfortunately, acid reflux is often wrongly treated as a condition which involves the production of too much acid. It is in fact, the stomach finding it difficult to digest the foods, most commonly as a result not having enough acid to complete digestion and why medications (see later) which further reduce stomach acid have serious and deadly side effects on health, the digestive process and the gut microbiota. Acid reflux affects about 20% of the adult population and is much higher in older people which is consistent with the studies showing lower stomach acid as we age.
 Adbi. 1976; Martinsen et al., 2005.
 Carrion and Egan, 1990.
 Husebye et al., 1992.
 Machado et al., 2008.
 Amir et al., 2013.
 Usai et al., 1995.
Research into the gut microbiome has ramped up over the past decade thanks to high investments over 100 million dollars by the US Governments in the Human Microbiome Project in 2007 as well as large sums from companies and private sources not wanting to be left behind as its importance for our health has become more widely recognised and understood by the mainstream. There is now a tsunami wave of information coming through on the gut microbiome, literally thousands of new studies and increasing each year.
Until recently the positive effects of the gut microbiome on our digestive system and health has been severely under rated. Wisdom of Chinese doctors from centuries ago, who somehow knew that the intestines were not merely a digestive organ, but the centre of health and well being. Hippocrates was recoded as saying that all illness begins in the gut. Throughout history from the Egyptians till around 80 years ago medicine and the bowels were frequently mentioned in the same sentence.
Even today the nomadic Maasai tribes in Africa attribute most illnesses to the effect of “pollutants” that block or inhibit digestion. In these communities the plants are used to cure diseases served mainly as strong purgatives and emetics; they "cleanse" the body and digestive system from polluting substances. While studies of the great apes show they self-medication to control intestinal parasite infections and gut problems across Africa. Chimpanzees (Pan troglodytes) for example, swallow the leaves of certain plant species whole, without chewing to aid expulsion of certain parasites. Swallowing rough or bristly leaves increases gut motility causing expulsion of adult worms, which disrupts the nematode’s life cycle and likely reduces worm burdens. Even carnivores first eat the guts of their kill and get all the intestinal bacteria. We seem to be the only ones who have forgotten the importance of the gut.
We now know the gut is the cornerstone of health and inflammation in the body. The first theory to explain the link between the gut and inflammation, which underlies all the chronic diseases we suffer from, was put forward in 1907, when Elie Metchnikoff proposed that tissue destruction (disease) and senescence (ageing) throughout the body were consequences of chronic systemic inflammation, which occurred as a result of increased permeability in the colon and the escape of bacteria and their products into the blood. He believed that these bacterial products activated our immune response (macrophages) and that the resulting inflammatory response caused deterioration of surrounding tissues and that this macrophage “intoxification” had systemic effects and led to deterioration of even distant tissues. And he was right.
 Bussmann et al., 2006.
 MCLennan and Huffman, 2012.
 Huffman and Caton, 2001.
Growing up as a child in the 60’s there was lots of space to play on the street, in the big back yards, nearby parks, creeks, the beach and lots of green spaces. While we we have lost a lot of these spaces research is showing that the more “green” we are surrounded with the the healthier it is for us. We exhibit more than just a preference for natural scenes and settings; we suffer health problems when we lose contact with our green surrounds. Increasing evidence indicates that nature provides restorative experiences that directly affect people's physical, social and mental well-being and health in a positive way including decreased mortality.
A recent study found that living in more densely vegetated areas was associated with fewer deaths from causes other than accidents. Using data from the Nurses’ Health Study researchers estimated a 12% lower rate of non-accidental death between women who lived in the most densely versus least densely vegetated areas. When looking at specific causes of death, the researchers estimated a 41% lower rate of kidney disease mortality, a 34% lower rate of respiratory disease mortality, and a 13% lower rate of cancer mortality in the women who lived in the greenest areas, compared with those in the least green areas. A study in the Netherlands found a lower prevalence of diseases in areas with more green space, including coronary heart disease and diabetes. In a cross-sectional study of 11,404 adults in Australia the odds of hospitalization for heart disease or stroke was 37% lower, and the odds of self-reported heart disease or stroke was 16% lower, among adults with highly variable greenness around their home, compared to those in neighborhoods with low variability in greenness. The odds of heart disease or stroke decreased by 7% per unit with every 25% increase in the level of greenness. In an interesting experiment where 14 children undertook two, 15 min bouts of cycling at a moderate exercise intensity while in one situation viewing a film of cycling in a forest setting and another with no visual stimulus. The systolic blood pressure (the top or higher number) 15 minutes after exercise was significantly lower following green exercise compared to the control condition. So if it works for kids it should also work for us we get older.
The rise in obesity is well documented and while there are many contributing factors a systematic review of green space research from sixty studies reported the majority (68%) of papers found a positive association between green spaces and obesity-related health indicators. One study found that increased vegetation was associated with reduced weight among young people living in high population densities and across eight European cities, people were 40% less likely to be obese in the greenest areas. Overall, the majority of studies found some evidence of a relationship with weight and green space. The lower rates of obesity, adverse health and improved health outcomes may be attributable to higher levels of physical activity, such as neighborhood walking which is positively influenced by the natural environment. Walking is the most popular physical activity particularly as we age, and levels of recreational walking have been linked the distance to and attractiveness of local parks and ovals. Many studies have reported that adults with access to a large high-quality park within walking distance (within 1600 m) from home have elevated levels of walking and and in general live longer. In a review of 50 studies twenty studies (40%) reported a positive association between green space and physical activity, including older adults.
Being around vegetation can lead to better mental health and less stress, positive emotions, focus and attention, as well as reduced stress. While walking itself can reduce stress, walking in a natural setting provides greater stress-relieving benefits. Accessible green spaces are ‘escape facilities’, and lack of access to green space contributes to poor mental health. Some of the more potent restorative effects of nature relate to being able to ‘get away’ from everyday settings and immerse oneself in an extensive natural setting that creates a sense of being in a ‘whole other world’.
Perhaps as we decide to age healthier we need to spend more time near green spaces.