Chronic Inflammation

Inflammation is part of the body's defense mechanism. It is the process by which the immune system recognizes and removes harmful stimuli and begins the healing process. These stimuli can be in the form of a foreign invader, such as bacteria or viruses, where your body’s white blood cells and the things they produce go into defense mode. Or it can be in the form of an injury where inflammation helps fight injury and infection. But it doesn’t just happen in response to injury and illness.

An inflammatory response can also occur when the immune system goes into action without an injury or infection to fight. Since there’s nothing to heal, the immune system cells that normally protect us begin to destroy healthy arteries, organs and joints. This can lead to auto-immune diseases.

There are generally two types of inflammation: acute and chronic.

Acute Inflammation
Tissue damage due to trauma, microbial invasion, or noxious compounds all induce acute inflammation. It starts rapidly, becomes severe in a short time and symptoms may last for a few days for example cellulitis or acute pneumonia. Subacute inflammation is the period between acute and chronic inflammation and may last 2 to 6 weeks.

Chronic Inflammation
In chronic inflammation, the inflammatory process may begin even if there is no injury, and it does not end when it should. Why the inflammation continues is not always known. Chronic inflammation may be caused by infections that don’t go away, abnormal immune reactions to normal tissues, or conditions such as obesity.

Diseases Linked to Chronic Inflammation

Chronic inflammatory diseases such as diabetes, cardiovascular disease, cancer, arthritis, COPD, and Alzheimer's are the most significant cause of death in the world. 

According to the American Diabetes Association, 30.3 million people or 9.4% of the American population, had diabetes in 2015 and it was the 7th leading cause of death in the United States.

Researchers discovered that in people with type 2 diabetes, cytokine levels are elevated inside fat tissue. Their conclusion: Excess body fat, especially in the abdomen, causes continuous (chronic), low levels of abnormal inflammation that alters insulin's action and contributes to the disease.

As type 2 diabetes starts to develop, the body becomes less sensitive to insulin and the resulting insulin resistance also leads to inflammation. A vicious cycle can result, with more inflammation causing more insulin resistance and vice versa. Blood sugar levels creep higher and higher, eventually resulting in type 2 diabetes.

NIH Study - The Role of Inflammation in Diabetes: Current Concepts and Future Perspectives

Does inflammation cause diabetes? It's not as simple as that, however, researchers know for sure that inflammation is somehow involved in the development of type 2 diabetes.

Cardiovascular Disease
Cardiovascular disease (CVD) accounts for one out of every three deaths or approximately 800,000 deaths in the United States.

Many clinical studies have shown strong and consistent relationships between markers of inflammation and cardiovascular disease prediction. Furthermore, Atherosclerosis is a pro-inflammatory state with all the features of chronic low-grade inflammation and leads to an increase in cardiovascular events such as myocardial infarction, stroke, among others.

Immune system cells that cause inflammation contribute to the buildup of fatty deposits in the lining of the heart’s arteries. “These plaques can eventually rupture, which causes a clot to form that could potentially block an artery. When blockage happens, the result is a heart attack,” says James Gray, MD, a cardiologist at the Scripps Center for Integrative Medicine.

Over time, chronic inflammation can cause DNA damage and lead to cancer.

The latest evidence seems to suggest that when a group of cells becomes cancerous and begins the tumor creation phase, they hijack other cells such as fibroblasts, and immune cells into the forming tumor. The incorporation of these immune cells gives them some level of protection against the body's immune system itself. This is all made possible when the tumor is enmeshed in a pro-inflammatory environment.

While the immune system has the ability to seek out and destroy cancerous tumors, the resulting inflammation not only blocks anti-tumor immunity, but it exerts direct tumor-promoting signals and functions onto epithelial and cancer cells. This is the paradoxical trade-off that evolution has dumped on us.

So, the key take-away here is how to maintain the benefits of immunity and its accompanying inflammation, while avoiding the pro-cancerous environment that that inflammation creates. What we want is the swift and immediate benefits of “acute” inflammation, and what we don’t want is the slow buildup of “chronic” inflammation.

Arthritis and Joint Diseases
These affect approximately 350 million people worldwide and nearly 43 million people in the United States or almost 20% of the population.

Chronic Obstructive Pulmonary Disease (COPD)
The third most common cause of death in the United States in 2014, and nearly 15.7 million Americans (6.4%) were reported to have been diagnosed with COPD.

Chronic airway inflammation has been indicated as a major risk factor in COPD and has been suggested to be associated with an increased risk of cancer, including lung cancer. Therefore, it can be hypothesized that COPD and lung cancer may share chronic inflammation as one of the common pathogenic mechanisms.

In older adults, chronic low-level inflammation is linked to cognitive decline and dementia.

Amyloid beta are peptides (amino acids) that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. These amyloid-beta molecules can aggregate into forms that are toxic to nerve cells.

Amyloid-beta fragments are believed to be one of the main causes of Alzheimer’s disease, accumulating in the brain and leading to brain cell death.

The latest experiments have shown that increasing the markers for inflammation and the subsequent increase in inflammation levels lead to higher levels of amyloid-beta. 

Causes of Chronic Inflammation

C-reactive protein (CRP) is used to measure the amount of inflammation in the body. CRP concentrations between 2 and 10 mg/L are considered as metabolic inflammation: metabolic pathways that cause arteriosclerosis and type II diabetes mellitus. Once inflammation subsides, CRP level falls quickly because of its relatively short half-life.

Increasing age is positively correlated with elevated levels of several inflammatory molecules. The age-associated increase in inflammatory molecules may be due to mitochondrial dysfunction or free radical accumulation over time and other age-related factors like increase in visceral body fat.

Many studies reported that fat tissue is an endocrine organ, secreting multiple adipokines and other inflammatory mediators. Some reports show that the body mass index of an individual is proportional to the amount of pro-inflammatory cytokines secreted. Metabolic syndrome typifies this well.

A diet rich in the following foods is associated with a higher production of pro-inflammatory molecules, especially in individuals with diabetes or overweight individuals.
  • Simple and refined carbohydrates (sugar, white flour, white rice)
  • Artificial trans-fats (hydrogenated trans-fats)
  • Oils high in Omega-6 (vegetable oils) - Omega-6 fatty acids are essential for a healthy diet, so instead of avoiding them, it may be better to control the amounts while balancing their intake with Omega-3 fatty acids. A ratio of 1 to 1 or even 2 to 1, Omega-3 to Omega-6 is ideal.
  • Excessive Alcohol
  • Processed meat that contains more advanced glycation end products (AGEs).

Cigarette smoking is associated with lowering the production of anti-inflammatory molecules and inducing inflammation.

Low Sex Hormones
Low testosterone and chronic inflammation are two interconnected health issues that have gained increasing attention in the medical community. Here's an overview of their relationship:

Testosterone's Role in the Body: Testosterone, a primary male sex hormone, plays a vital role in various bodily functions including muscle mass, bone density, and the production of red blood cells. It also impacts mood, energy levels, and sexual function.

Understanding Chronic Inflammation: Chronic inflammation is a prolonged inflammatory response that can negatively impact tissues and organs. It's associated with various diseases such as rheumatoid arthritis, heart disease, and diabetes. Unlike acute inflammation, which is a necessary part of the body's healing process, chronic inflammation can be harmful.

Inflammatory Markers: Research has shown that low levels of testosterone are often found in conjunction with elevated markers of inflammation, such as C-reactive protein (CRP) and interleukin-6 (IL-6).
Testosterone as an Anti-Inflammatory Agent: Testosterone can act as an anti-inflammatory agent. Lower levels of testosterone may lead to an increase in inflammatory processes.

Impact on Chronic Conditions: Conditions associated with chronic inflammation, like metabolic syndrome and obesity, are also often linked with reduced testosterone levels. This relationship suggests a bidirectional link, where low testosterone can contribute to the development of chronic inflammation and vice versa.
Mechanisms of Interaction:

Hormonal Imbalance: Hormonal imbalances involving testosterone can influence the regulation of the immune system, potentially leading to increased inflammatory responses.
Body Composition: Testosterone plays a role in maintaining muscle mass and reducing fat mass. Lower testosterone levels can lead to increased body fat, which is associated with higher levels of inflammation.

Stress and Sleep Disorders
Both physical and emotional stress is associated with inflammatory cytokine release. Stress can also cause sleep disorders. Since individuals with irregular sleep schedules are more likely to have chronic inflammation than consistent sleepers, the sleep disorder is also considered as one of the independent risk factors for chronic inflammation.

Reducing Chronic Inflammation

Exercise and Lose Weight
In human clinical trials, it is shown that energy expenditure through exercise lowers multiple pro-inflammatory molecules and cytokines independently of weight loss.

It is largely known that adipose tissue in obese or overweight individuals induces low-grade systemic inflammation. Regular exercise is helpful not only in controlling weight but also decreasing the risk of cardiovascular diseases and strengthening the heart, muscles, and bones.

Stress Reduction and Sleep
Chronic stress contributes to inflammation.

Chronic psychological stress is linked to greater risk for depression, heart disease and the body losing its ability to regulate the inflammatory response and normal defense. Yoga and meditation are helpful in alleviating stress-induced inflammation and its harmful effects on the body.

Find your best way to eliminate long-term, chronic stress. “We may not be able to change many of the stressful situations we encounter in life, but we can change our response and perception by learning to manage stress better,” Dr. Gray says.

Overnight sleep (ideally at least 7 to 8 hours) helps stimulate human growth hormones and testosterone in the body to rebuild itself.

Eat Right
Vitamin D is directly linked to reduced inflammation and increased immune response.
Read more - Vitamin D (Coming Soon!)

It is important to avoid eating simple sugars, refined carbohydrates, high-glycemic foods, trans fats, and hydrogenated oils. Consuming whole grains, natural foods, plenty of vegetables and fruits such as avocados, cherries, kale, and fatty fish like salmon is helpful in defeating inflammation.

Eat more fruits and vegetables and foods containing omega-3 fatty acids. Some of the best sources of omega-3s are cold water fish, such as salmon and tuna, and tofu, walnuts, flax seeds and soybeans. 

The Mediterranean diet is a perfect example of an anti-inflammatory diet. This is due to its focus on fruits, vegetables, fish and whole grains, and limits on unhealthy fats, such as red meat, butter and egg yolks as well as processed and refined sugars and carbs.

Foods that can be helpful in removing inflammation triggers: 
  • Low-glycemic diet: Diet with a high glycemic index is related to high risk of stroke, coronary heart disease, and type 2 diabetes mellitus. It is beneficial to limit consumption of inflammation-promoting foods like sodas, refined carbohydrates, fructose corn syrup in a diet.
  • Reduce intake of total, saturated fat and trans fats: Some dietary saturated and synthetic trans-fats aggravate inflammation, while omega-3 polyunsaturated fats appear to be anti-inflammatory. Processed and packaged foods that contain trans fats such as processed seed and vegetable oils, baked goods (like soybean and corn oil) should be reduced from the diet.
  • Fruits and vegetables: Blueberries, apples, Brussels sprouts, cabbage, broccoli, and cauliflower, that are high in natural antioxidants and polyphenols and other anti-inflammatory compounds, may protect against inflammation.
  • Fiber: High intake of dietary soluble and insoluble fiber is associated with lowering levels of IL-6 and TNF-alpha. 
  • Nuts: such as almonds is associated with lowering risk of cardiovascular disease and diabetes.
  • Green and black tea polyphenols: Tea polyphenols are associated with a reduction in CRP in human clinical studies. 
  • Curcumin: a constituent of turmeric causes significant patient improvements in several inflammatory diseases especially in animal models.
  • Fish Oil - The richest source of the omega-3 fatty acids. Higher intake of omega-3 fatty acids is associated with lowering levels of TNF-alpha, CRP, and IL-6.
  • Mung bean: Rich in flavonoids (particularly vitexin and isovitexin). It is traditional food and herbal medicine known for its anti-inflammatory effects.
  • Micronutrients: Magnesium, vitamin D, vitamin E, zinc and selenium). Magnesium is listed as one of the most anti-inflammatory dietary factors, and its intake is associated with lowering of hsCRP, IL-6, and TNF-alpha activity. Vitamin D exerts its anti-inflammatory activity by suppressing inflammatory mediators such as prostaglandins and nuclear factor kappa-light-chain-enhancer of activated B cells. Vitamin E, zinc, and selenium act as antioxidants in the body.

Read More:
  • Creating an Anti-Inflammatory Diet or Foods That Fight Chronic-Inflammation (Coming Soon!)
  • Reducing Chronic Inflammation (Coming Soon!)

Going a Step Further - Testing for Inflammation
The most common way to measure inflammation is to conduct a blood test for C-reactive protein (hs-CRP), which is a marker of inflammation. Doctors also measure homocysteine levels to evaluate chronic inflammation. Finally, physicians test for HbA1C - a measurement of blood sugar - to assess damage to red blood cells.