Inflammation: A Tightly Regulated Biological Response that, if Uncontrolled, Can Turn out Fateful

Jesse Oswald • December 16, 2024

Key points

  • Inflammation is a physiological, tightly regulated, protective process in response to harmful stimuli, such as pathogens, trauma, chemicals, etc.
  • Chronic inflammation is associated with the development of severe chronic health issues, such as cardiovascular disease, type II diabetes, cancer, neurodegenerative and autoimmune diseases
  • The most important causative factors of chronic inflammation are obesity and specifically visceral fat, stress, sleep disturbances, environmental chemicals, and unhealthy dietary constituents and patterns
  • Regular exercise, adherence to healthy dietary patterns, and mind-body interventions have the potential to decrease or even reverse chronic inflammation


Over the last decade, there has been much discussion about inflammation and whether there is such a thing as chronic inflammation, as well as anti-inflammatory agents in terms of food and botanical constituents that could effectively battle it. It seems that it all adds up since chronic inflammation does exist and is at its peak rate, probably due to the contemporary lifestyle. In this post, topics such as what inflammation is as a biological process and what may cause it, its relation to lifestyle factors such as diet, exercise, and environmental chemicals, as well as its implication with chronic severe diseases such as obesity, type II diabetes, and cardiovascular disease will be discussed.


What really inflammation is and how is it caused


Inflammation is a physiological, tightly regulated, protective process in response to harmful stimuli. Insults that can trigger inflammation include:

  • Infection from pathogenic microorganisms like bacteria, viruses, or fungi
  • Tissue damage from trauma
  • Necrotic cells of human tissue remaining after fighting a harmful agent
  • External injuries like scrapes 
  • Effects of irritants and toxic compounds like chemicals 
  • Irradiation


The goal of inflammation is to destroy the harmful stimuli that initiated it and start the repair process, restoring the involved tissues to their pre-inflamed state and thus re-establishing homeostasis. Therefore, acute inflammation, which resolves in a few days after eradicating the inflammatory stimulus, is a beneficial, biologically appropriate process required for regaining tissue homeostasis after damage within the human body has occurred. Symptoms associated with signs of acute inflammation include redness, heat, swelling, pain, and temporary loss of function at the site of inflammation.


The acute inflammatory response involves the recruitment of immune system cells, known as leucocytes, such as neutrophils, macrophages, monocytes, etc. These cells release inflammatory mediators, including reactive oxygen species (ROS) and inflammatory cytokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-a (TNF-a) to kill the harmful agent. Since the goal of the acute inflammatory response is threat removal, without specificity or selectivity, collateral tissue damage is the inevitable consequence of massive ROS and cytokine production from leucocytes. Nevertheless, the resolution and self-termination of inflammation and the return to baseline status in days to weeks following the eradication of the inflammatory stimulus ensures survival and is not a pathological response.


If this elegant coordination of immune system adaptations fails to resolve or resolves inadequately since the inflammatory stimuli persist or propagate, inflammation can become chronic, self-directed, and thus dangerous. Specifically, the chronicity of inflammation is associated with excessive human tissue damage and various severe disease states, including inflammatory bowel disease, cancer, type II diabetes, heart disease, and autoimmune disorders, such as rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus. 


Although this relationship is very complicated and has not yet been elucidated, possible mechanisms connecting chronic inflammation with multiple health conditions include its association with elevated blood glucose levels and insulin resistance, with sodium, fluid retention, and hypertension, as well as with persistently elevated levels of cytokines such as IL-6 and C-reactive protein (CRP).


As mentioned above, chronic low-grade inflammation is associated with the development of severe chronic health issues, some of them being among the top causes of death worldwide, such as cardiovascular disease, type II diabetes, obesity, cancer, and neurodegenerative diseases. It could be actually argued that inflammation is not only associated with the disease condition itself but could also be involved in its pathogenesis and progression.   


The common feature in these disease states is a silent low-grade inflammatory process, reflected as an increase in systemic plasma concentrations of inflammatory markers, such as cytokines (IL-1, IL-6, TNF-a, CRP, etc.). For instance, higher concentrations of inflammatory markers such as IL-6, TNF-a, and CRP have been shown to be associated with higher cardiovascular risk. 


So, how can this chronic silent inflammatory process be triggered? Lifestyle factors, including smoking, alcohol consumption, poor diet, low levels of physical activity, exposure to environmental chemicals, and increased stress, contribute to the development of low-grade inflammation. Hence, strategies to improve overall lifestyle, including adhering to a healthy diet, regular exercise, adequate sleep, and social support, may be an effective approach to prevent chronic inflammation by modifying risk factors for chronic diseases associated with it.


The most important causative factors of chronic inflammation are discussed below. 


Obesity and its central role in chronic inflammation


The vast majority of human fat tissue is of the white type; this type of fat is mainly located beneath the skin (subcutaneous adipose tissue) and around internal organs (visceral adipose tissue). White adipose tissue is not only an energy storage place but is also metabolically active, regulating several metabolic pathways, including immunity and inflammation. Specifically, adipocytes secrete numerous hormones and cytokines, collectively called adipokines. Some of them are pro-inflammatory, such as the hormones leptin and resistin, and the cytokines IL-6, CRP, and TNF-a, and some of them are anti-inflammatory, such as the hormone adiponectin. 

While research has shown an association between both central obesity (visceral fat) and total obesity and inflammation, increased visceral fat is the primary source of chronic systemic low-grade inflammation. 


Although the association is not clear yet, it seems that the link between central obesity and inflammation is the oversecretion of pro-inflammatory adipokines and free fatty acids by the visceral fat of obese individuals. 


More specifically, obesity is linked to the enlargement of adipocytes (hyperplasia), leading to hypoxic conditions within these cells. As a result, a local inflammatory response is triggered, with the recruitment of immune cells, such as macrophages, and the subsequent accumulation of the pro-inflammatory cytokines IL-6 and TNF-a. IL-6, in turn, stimulates CRP production in the liver and the employment of more immune cells. Simultaneously, since fat tissue has a limited capacity to store energy, once this is exceeded, like in hyperplastic fat cells, lipolysis occurs within the cells, causing a release of free fatty acids into the circulation. Free fatty acids reinforce the release of pro-inflammatory cytokines and also directly mediate the inflammatory process.


The association between visceral fat and inflammation is actually proportional, meaning the higher the body weight and the body fat, the higher the levels of the pro-inflammatory adipokines and, therefore, the higher the level of inflammation.


It’s thus becoming evident that obesity predisposes to a pro-inflammatory state. Inflammation results in the massive production of ROS, also leading to oxidative stress. Both oxidative stress and inflammation statuses are strongly associated with chronic severe health complications, including cardiovascular disease, insulin resistance, hypertension, type II diabetes, obstructive sleep apnea, rheumatoid arthritis, dementia, and cancer.  Therefore, obesity, especially large visceral fat volumes (central obesity), through its chronic inflammatory components, is involved in the pathogenesis and progression of cardiometabolic, neurodegenerative, and autoimmune diseases.


Inflammation caused by dysregulated sleep patterns


Lifestyle behaviours like sleep have been linked to heightened inflammatory responses. 

Moreover, sleep issues have been associated with an increased risk of multiple inflammatory disorders, including cardiovascular disease and neurodegenerative diseases. 


So, could chronic inflammation be the link connecting sleep issues with adverse public health outcomes?

Indeed, sleep disturbances in terms of sleep deprivation, insomnia, sleep restriction (sleeping less than 5 hours per night), and sleep fragmentation (nocturnal waking for ≥ 90 minutes) lead to increased inflammation due to changes in the immune system that trigger inflammatory responses.


A possible mechanism is that sleep disturbances induce a shift in the temporal profile of inflammatory responses, with increased production of the pro-inflammatory cytokines IL-6 and TNF-a during the day rather than during the night, leading to excessive levels of inflammation. Due to the increased production of IL-6, there is also a subsequent overproduction of CRP, further propagating inflammation. If the sleep disturbance is persistent, it leads to sustained activation of the inflammatory response and, thus, chronic inflammation.


Inflammation caused by chronic stress


Chronic stress in major life domains (relationships, work, finances) stimulates chronic inflammation in both men and women, which is reflected in the elevated CRP levels.


Additionally, emerging research suggests that social support and network may have a role in mitigating the psychological impact of major life stressors, thus attenuating their potential to cause chronic inflammation.


Moreover, mind-body interventions such as tai chi and meditation are emerging as promising strategies to reduce stress and thus decrease or even reverse inflammation, with effects on the severity or even the prevention of pathologies related to chronic inflammation, such as neurodegenerative and autoimmune diseases. 


Inflammation caused by environmental chemicals


Chemical exposure in the environment, including long-term exposure to polycyclic aromatic hydrocarbons (PAHs), perfuoroalkyl substances (PFAs), and metal exposure, is responsible for causing chronic inflammatory responses. 


PFAs have significant bioaccumulation potential and are widely used in food packaging, household cleaning products, cosmetics, etc. 

PAHs are a group of chemicals formed during the incomplete combustion of coal, oil, gas, and garbage, including vehicle exhaust, coal tar, wildfires, agricultural burning, etc. 


Regarding metal exposure, arsenic is a toxic metal widely distributed in the environment and is present in soil, food, and water, leading to unavoidable human exposure. Cadmium is mainly released from nickel-cadmium batteries, plastic stabilizers, fossil fuel combustion, and garbage incineration. Mercury pollution primarily comes from burning coal, non-ferrous metals, and cement production.


All these environmental pollutants can enter the human body through the respiratory tract, digestive tract, and skin and interact with the immune system, inducing a chronic inflammatory response and, thus, the possibility of chronic inflammatory diseases, such as cancer and autoimmune disorders.


The implication of exercise with chronic inflammation


Physical inactivity is one of the most important lifestyle factors associated with persistent systemic low-grade inflammation and, thus, an increased likelihood of inflammatory diseases. On the other hand, regular exercise possesses anti-inflammatory effects, thereby reducing disease risk. 


The anti-inflammatory effects of regular exercise are attributed to several mechanisms, the most critical of which are increased fat oxidation and reduced visceral body fat stores. Specifically, exercise results in an increased skeletal muscle capacity to burn fat, resulting in increased fat oxidation in mitochondria and decreased overall lipid storage inside cells. Consequently, exercise helps limit visceral fat accumulation and adipose tissue expansion. Since fat tissue and visceral fat, in particular, are metabolically active and release pro-inflammatory mediators, as stated before, exercise limits inflammation activation by downregulating these pro-inflammatory mediators, including cytokines. Specifically, it has been shown that regular exercise reduces the levels of IL-1 and IL-6.

Moreover, active skeletal muscles secrete molecules known as myokines, which help counterbalance the pro-inflammatory effects of cytokines. 


Since the inflammatory effects of physical inactivity run mostly through its impact on visceral fat and obesity, it could be supported that a link between physical inactivity, visceral fat accumulation (central obesity), and inflammation likely exists. However, the association between chronic systemic inflammation and physical inactivity is independent of obesity status. 


Collectively, regular physical activity and its associated fat loss may offer prevention and treatment for various chronic diseases associated with low-grade inflammation. It is inexpensive and without the side effects of many pharmacological therapies and could be viewed as a natural remedy for recovering part of the inflammatory burden caused by modern lifestyles.


The implication of diet with chronic inflammation


Primarily, nutrition serves as the source of essential nutrients, providing energy and substrates for numerous metabolic functions. 

In cases of obesity and, thus, chronic inflammation, a dietary pattern encompassing caloric restriction has been proven effective in reducing inflammation and metabolic dysfunction related to obesity status.


Besides the caloric restriction that can reduce chronic inflammation by decreasing visceral fat, several studies demonstrate an inverse association between inflammatory markers and adherence to healthy dietary patterns. Specifically, nutritional factors such as dietary fiber, antioxidants, and omega-3 fatty acids have been associated with decreased concentrations of inflammatory markers. In contrast, dietary factors, such as trans and saturated fat, sugar, and sodium, have been associated with increased levels of inflammation. 


  • Dietary fiber
  • Fiber-rich diets are often associated with a high intake of antioxidants and complex carbohydrates, both of which may reduce inflammation. Another anti-inflammatory mechanism of fiber is its conversion into immune-regulating substances, such as short-chain fatty acids, by the gut microbiota in the colon. These substances activate signaling pathways, eventually decreasing the inflammatory response by reducing the pro-inflammatory cytokines IL-6, TNF-a, and CRP production.
  • Polyphenols
  • Polyphenols are a heterogeneous group of bioactive substances found in plant-based foods. They are known to have potent antioxidant and anti-inflammatory effects, thanks to their ability to reduce ROS and the pro-inflammatory cytokines IL-6 and TNF-a, respectively.
  • Omega-3 fatty acids
  • Omega-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are found in fish and fish oils and are considered anti-inflammatory. They have been shown to improve markers of cardiovascular disease, rheumatoid arthritis, and cancer cachexia, all disease states associated with chronic inflammation.
  • Trans fatty acids
  • Trans fatty acids have predominantly pro-inflammatory properties by activating inflammatory pathways and increasing oxidative stress through increased ROS production. Their primary source is partially hydrogenated oils, usually the result of industrial food processing. They are also partly derived from ruminant animal products. 
  • Saturated fat
  • Similarly to trans fatty acids, saturated fat also seems to exert pro-inflammatory effects due to increased production of ROS and activation of pro-inflammatory pathways.
  • Sugar
  • Food products with high levels of free-added sugar seem to have enhanced pro-inflammatory effects and may be linked to the development of chronic diseases associated with inflammatory processes, such as atherosclerosis, cancer, and Alzheimer’s disease. A possible explanation is a chronic and exaggerated increase in blood glucose caused by such foods, which can lead to the excessive formation of advanced glycation end products (AGEs). AGEs may cause oxidative stress and trigger inflammatory responses. 
  • Dietary patterns
  • High adherence to the Mediterranean diet or the DASH (Dietary Approaches to Stop Hypertension) has been associated with decreased CRP, IL-6, and TNF-a levels, as well as oxidative stress biomarkers. The high content of anti-inflammatory nutrients such as omega-3 fatty acids, dietary fiber, complex carbohydrates, and polyphenols may explain the consistent anti-inflammatory effects of such diets, which are rich in fruits, vegetables, legumes, and whole grains.
  • Also, adherence to a Paleolithic diet, rich in plant-based and non-processed animal products but low in processed foods, added sugars, salt, and dairy, has also been linked to a decrease in inflammation markers, especially CRP and oxidative biomarkers. In contrast, the ‘’Western’’ dietary pattern rich in processed meats, refined grains, and sugary beverages is linked to increased inflammatory markers.


To sum up, the battlefronts of chronic inflammation are multiple, and if silently working chronically without us making lifestyle changes to decrease them or even completely eradicate them, they can lead to severe health issues that can compromise quality of life and reduce lifespan. However, the ability of inexpensive and undemanding remedies, such as diet, exercise, meditation, etc., to effectively combat chronic inflammation is in front of our eyes and the palm of our hands, so it should not be neglected.


References

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4. Ellulu MS, Patimah I, Khaza’ai H, Rahmat A, Abed Y. Obesity and inflammation: the linking mechanism and the complications. Arch Med Sci. 2017;13(4):851-863. DOI: 10.5114/aoms.2016.58928


5. Hess JM, Stephensen CB, Kratz M, Bolling BW. Exploring the links between diet and inflammation: Dairy foods as case studies. Adv Nutr. 2021;12(Suppl1):1S-13S. DOI: 10.1093/advances/nmab108


6. Irwin MR, Sleep and inflammation: partners in sickness and in health. Nat Rev Immunol. 2019;19(11):702-715. DOI: 10.1038/s41577-019-0190-z


7. Khanna D, Khanna S, Khanna P, Kahar P, Patel BM. Obesity: A chronic low-grade inflammation and its markers. Cureus. 2022;14(2):e22711. DOI: 10.7759/cureus.22711


8. Liu Y, Zhang Z, Han D, Zhao Y, Yan X, Cui S. Association between environmental chemicals co-exposure and peripheral blood immune-inflammatory indicators. Front Public Health. 2022;10:980987. DOI: 10.3389/fpubh.2022.980987


9. Oronsky B, Caroen S, Reid T. What exactly is inflammation (and what is it not?). Int J Mol Sci. 2022;23(23):14905. DOI: 10.3390/ijms232314905


10. Ricordi S, Garcia-Contreras M, Farnetti S. Diet and inflammation: Possible effects on immunity, chronic diseases, and life span. J Am Coll Nutr. 2015;34Suppl1:10-13. DOI: 10.1080/07315724.2015.1080101


11. Sotos-Prieto M, Bhupathiraju SN, Falcon LM, Gao X, Tucker KL, Mattei J. Association between a Healthy Lifestyle Score and inflammatory markers among Puerto Rican adults. Nutr Metab Cardiovasc Dis. 2016;26(3):178-184. DOI: 10.1016/j.numecd.2015.12.004


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An Ounce of Prevention - Hyperion Health Blog

A woman is helping an older woman do exercises on an exercise ball in a gym.

What is a Kinesiologist?

By Jesse Oswald • January 29, 2025
What is a Kinesiologist?
A woman is wearing an oxygen mask while running on a treadmill.

Predicting Medical Costs with VO2max

By Jesse Oswald • January 20, 2025
Highlights Healthcare expenses are skyrocketing, with consumers and employers facing the significant brunt. Identifying those likely to get sick is critical as our resource-strapped healthcare system should focus on those likely to become the most significant burden to the system. VO2 max is a crucial longevity indicator that can also accurately predict healthcare expenses. The rampant chronic disease epidemic and the resulting surge in medical expenses is one of the most dire problems of modern societies, probably only second to climate change. Healthcare inflation is on a meteoric rise, and for those with limited or no healthcare coverage, a medical emergency is the equivalent of personal bankruptcy. A dire problem for employers In the US, employers and consumers who face rising health insurance premiums and astronomical out-of-pocket medical expenses feel the brunt of rising healthcare costs. Such is the problem that even large, well-capitalized corporations choose to send employees overseas for specific medical procedures since the cost of traveling and treatment in a foreign country is lower than the cost of care in the US. Another startling example is the infamous "northern caravan," a term that describes people with diabetes in the northern states who travel to Canada to secure their insulin supply. According to McKinsey , a survey conducted among over 300 employers highlighted that the average increase in the cost of health benefits over the past three years has been within the range of 6 to 7 percent. This survey also indicated that any rate increases exceeding 4 to 5 percent were deemed unsustainable. Interestingly, 95 percent of the surveyed employers expressed willingness to contemplate reducing benefits if costs surged by 4 percent or more. The primary cost-control measures that these employers indicated they might explore included elevating the portion of premium costs covered by employees and a potential transition to high-deductible health plans. Why is Breath Analysis relevant? Vis-a-vis this problem, the early and accurate estimation of who will get sick and how much they will cost is as critical as the treatment itself. The reason is that no other method of accurately identifying at-risk populations exists; it helps focus our scarce prevention resources and attention on those most in need. Breath analysis, AKA VO2max or metabolic testing, is an assessment that reveals two key biomarkers that provide significant predictive value for one's likelihood of developing costly chronic conditions. These two biomarkers are VO2max and the Respiratory Exchange Ratio. In this article, we will dive into VO2max to understand why it's a critical reflection of our overall health and, consequently, a window into our future healthcare spend. What is VO2max? Let's start with the basics. What is VO2max? VO2 max is the maximum amount of oxygen the human body can absorb. It is measured in terms of milliliters of oxygen consumed per kilogram of body weight. The below formula below indicates how VO2max is calculated: The numerator indicates the volume of oxygen your heart, lungs, and cells can absorb, expressed in milliliters per minute. The denominator indicates the weight of the individual represented in kilograms. 
There are many different types of fats in this picture.

Dietary Fat: An Essential Dietary Component Rather than the root of all Nutritional Health Issues

By Jesse Oswald • January 13, 2025
Key points A total fat intake between 20-35% ensures sufficient intake of essential fatty acids and fat-soluble vitamins Omega-6 PUFAs are primarily found in vegetable oils, while omega-3 PUFAs are primarily found in fatty fish and fish oils Both omega-3 PUFAs and MUFAs have established benefits for cardiovascular disease TFAs are the only dietary lipids that have a strong positive relationship with cardiovascular disease Omega-3 PUFA supplementation increases the beneficial bacteria of the human microbiome Over the last three decades, there has been a great revolution against fat due to its suspected association with several nutritional health issues, especially cardiovascular disease. There was a tremendous amount of evidence that indicated dietary cholesterol and saturated fat as the main culprits of cardiovascular disease, thus morbidity and mortality. It was when all the low-fat and no-fat dairy products started to launch, promising even complete substitution of the cholesterol-lowering heart medication if these products were exclusively consumed. Let’s start from the beginning. Dietary fat intake can vary significantly and still meet energy and nutrient needs. International guidelines suggest a total fat intake between 20% and 35% of the daily caloric consumption. This range ensures sufficient intake of essential fatty acids and fat-soluble vitamins. Not only does the quantity of the ingested fat matter, but most importantly, its quality. Some dietary fats have beneficial effects, with a significant role in maintaining good health, while others may threaten it. Which are, after all, the dietary fats? Dietary fats is a rather heterogeneous group of organic compounds, including four main types of fat, which are elaborately described in the following sections of this article. Polyunsaturated fatty acids (PUFAs) Polyunsaturated fatty acids (PUFAs) have two or more carbon-carbon double bonds. Omega-6 PUFAs and omega-3 PUFAs are the main types of PUFAs and are classified according to the location of the first unsaturated bond (sixth and third carbon atom, respectively). Alpha-Linolenic acid (ALA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and eicosapentaenoic acid (EPA) are the most important omega-3 PUFAs. ALA is an essential fatty acid that can only be obtained from diet and can be converted into EPA and then to DHA, but the rate of this conversion is finite, approximately 7.0%–21% for EPA and 0.01%–1% for DHA. In the same way, the most important omega-6 PUFAs are linoleic acid (LA) and arachidonic acid (ARA). LA is an essential fatty acid that, in order to give rise to ARA, needs to be ingested through the diet as the human body cannot synthesize it. The recommended intake for total PUFA ranges between 5% and 10% of the total energy intake, while a total omega-3 PUFA intake of 0.5%–2% and a total omega-6 PUFA intake of 2.5%-5% is suggested. A dietary ratio of omega−6/omega−3 PUFA is recommended to be 1:1–2:1 to balance their competing roles and achieve health benefits. Omega-6 and omega-3 PUFAs Omega-6 PUFAs, in the form of LA, are plentiful in most crop seeds and vegetable oils, such as canola, soybean, corn, and sunflower oils. In contrast to omega-6 PUFAs, omega-3 PUFAs are obtained from a limited range of dietary sources. Flax, chia, and perilla seeds are rich in ALA, with significant amounts also detected in green leafy vegetables. The consumption of fatty fish, such as salmon, sardines, tuna, trout, and herring, provides high amounts of EPA and DHA. Besides fish and their oils, small amounts of omega-3 PUFAs are also detected in red meat like beef, lamb, and mutton. All the above dietary sources provide EPA, DPA, DHA, LA, and ARA in different amounts, and their intake is necessary for normal physiological function. PUFAs play a critical role in many chronic diseases, affecting human cells by regulating inflammation, immune response, and angiogenesis. Omega-3 PUFAs’ role against hypertriglyceridemia has been clarified, and research indicates that systematically consuming oily fish can contribute to general heart protection. Supplementation with omega-3 PUFAs could potentially lower the risk of several cardiovascular outcomes, but the evidence is stronger for individuals with established coronary heart disease. Moreover, adequate EPA and DHA levels are necessary for brain anatomy, metabolism, and function. Although the mechanisms underlying omega-3 PUFAs' cardioprotective effects are still poorly understood, several studies have been conducted in this direction. Unfortunately, that does not hold true for their omega-6 counterparts, for which controversial emerging data tend to show anti-inflammatory behavior that needs to be further studied. Monounsaturated fatty acids (MUFAs) In contrast to PUFAs, monounsaturated fatty acids (MUFAs) are easily produced by the liver in response to the ingestion of carbohydrates. The main MUFA is oleic acid, found in plant sources, such as olive oil, olives, avocado, nuts, and seeds, while minimal amounts are also present in meat, eggs, and dairy products. Specific guidelines around MUFAs’ dietary consumption do not exist. Therefore, MUFAs are recommended to cover the remaining fat intake requirements to reach the total daily fat intake goal. A growing body of research shows that dietary MUFAs reduce or prevent the risk of metabolic syndrome, cardiovascular disease (CVD), and hypertension by positively affecting insulin sensitivity, blood lipid levels, and blood pressure, respectively. Moreover, olive oil contains several bioactive substances, possessing anti-tumor, anti-inflammatory, and antioxidant qualities. According to a meta-analysis, consuming olive oil was linked to a lower risk of developing any sort of cancer, especially breast cancer and cancer of the digestive system. Another study found that an isocaloric replacement of 5% of the energy from saturated fatty acids (SFAs) with plant MUFAs led to an 11% drop in cancer mortality over a 16-year follow-up period. Therefore, including MUFAs in the everyday diet offers multifaceted benefits in chronic disease prevention and management, including cancer and general health promotion.  Saturated fatty acids (SFAs) Saturated fatty acids (SFAs) form a heterogeneous group of fatty acids that contain only carbon-to-carbon single bonds. Whole-fat dairy, (unprocessed) red meat, milk chocolate, coconut, and palm kernel oil are all SFA-rich foods. These fatty acids have distinct physical and chemical profiles and varying effects on serum lipids and lipoproteins. Stearic, palmitic, myristic, and lauric acids are the principal SFAs found in most natural human diets. Dietary practice and guidelines recommend limiting SFA intake to <10% of the total energy (E%), while the American Heart Association suggests an even lower intake of <7 E% because total saturated fat consumption and LDL-C levels are positively correlated. However, the role of SFAs in CVDs is quite complex, and the evidence is heterogeneous. In a recent study with a 10.6-year follow-up period, which included 195,658 participants, there was no proof that consuming SFAs was linked to developing CVD while replacing saturated fat with polyunsaturated fat was linked to an increased risk of CVD. Moreover, according to 6 systematic reviews and meta-analyses, cardiovascular outcomes and total mortality were not significantly impacted by substituting saturated fat with polyunsaturated fat. Even if these analyses were to be challenged, due to heterogenous evidence, the possible reduction in CVD risk associated with replacing SFAs with PUFAs in several studies may not necessarily be an outcome of SFAs’ negative effect but rather a potential positive benefit of PUFAs. Regarding SFAs' effect on different types of cancers, associations of their intake with an increased risk of prostate and breast cancer have been indicated. Conversely, a meta-analysis showed no link between SFA intake and a higher risk of colon cancer; similarly, consuming MUFAs, PUFAs, or total fat did not affect colon cancer risk. Hence, the role of SFA consumption in preventing, promoting, or having a neutral role in serious chronic diseases has not been fully elucidated yet. Trans fatty acids (TFAs) Trans fatty acids (TFAs) are created industrially by partially hydrogenating liquid plant oils or can be naturally derived from ruminant-based meat and dairy products. TFAs are highly found in commercial baked goods, biscuits, cakes, fried foods, etc. Guidelines regarding TFAs are stringent and limit TFA intake to <1% of energy or as low as possible. In 2015, the US Food and Drug Administration declared that industrial TFAs are no longer generally recognized as safe and should be eliminated from the food supply as their consumption is strongly linked to various CVD risk factors. Specifically, TFA intake raises triglycerides and increases inflammation, endothelial dysfunction, and hepatic fat synthesis, leading to a significantly increased risk of coronary heart disease (CHD). A meta-analysis suggested that increased TFA intake led to an increase in total and LDL-cholesterol and a decrease in HDL-cholesterol concentrations. Data also indicates that TFAs may influence carcinogenesis through inflammatory pathways, but the reported data are debatable. A recent study investigated the effects of all types of dietary fat intake on CVD risk. While PUFA, MUFA, and SFA intake were not linked to higher CVD risk, dietary TFA intake showed a strong association with CVD risk. Analysis indicated PUFA intake and CVD risk were inversely correlated, and the relative risk of CVD was reduced by 5% in studies with a 10-year follow-up. Dietary lipids and the human microbiome Dietary lipids also affect human microbiota composition. Studies have identified a close association between the human microbiome and metabolic diseases, including obesity and type 2 diabetes. Diets with a high omega-6 PUFA, SFA, and TFA intake increase the amount of many detrimental bacteria in the microbiome and reduce the amount of the beneficial ones, altering the microbiota composition and inducing inflammation via the secretion of pro-inflammatory cytokines. These bacteria may disrupt the gut barrier function, allowing lipopolysaccharides (LPS) translocation, which are bacterial toxins. This condition is linked to metabolic perturbations such as dyslipidemia, insulin resistance, non-alcoholic fatty liver disease (NAFLD), and CVD. On the contrary, omega-3 PUFA (EPA and DHA) supplementation increases beneficial bacteria and limits harmful ones, enhancing intestinal barrier functioning and preventing LPS translocation and its implications. Omega-3 PUFA supplementation has also been studied as a means of mental health disorders management, but the evidence is still controversial. A possible protective impact of fish consumption on depression has been suggested by various studies, as well as a possible protective effect of dietary PUFAs on moderate cognitive impairment. A recent review of meta-analyses indicated that omega-3 PUFA supplementation might have potential value in mental health disorders, but data credibility is still weak. Dietary lipids and obesity Last but not least, obesity and its management is another field that dietary lipids intake seems to impact with their mechanisms. A diet high in PUFA has been shown to lower the total mass of subcutaneous white adipose tissue (the predominant fat type in human bodies), reduce blood lipid levels, and improve insulin sensitivity. In a study comparing PUFA and MUFA isocaloric intake, PUFA was more advantageous and lowered visceral adiposity in patients with central obesity. By stimulating brown adipose tissue, which aids energy expenditure through its elevated thermogenic activity, omega-3 PUFAs seem to elicit these positive effects in fat tissue, thus being useful in preventing and/or managing obesity. Another related study compared PUFA to SFA overfeeding in dietary surplus conditions that aimed to increase weight by 3%. While SFA overfeeding led to weight gain, primarily through the expansion of the visceral adipose tissue, PUFA overfeeding also led to weight gain, but because of a greater expansion of lean tissue mass. To sum up, dietary fats are an essential part of the human diet with many important physiologic functions, including cell function, hormone production, energy, and nutrient absorption. Moreover, dietary fat consumption is associated with positive outcomes in regard to cardiovascular disease, metabolic syndrome, cancer, and depression. Therefore, there is no reason to demonize this valuable dietary component, incriminating it for irrelevant adverse health outcomes, primarily weight loss failure and obesity. References 1. Astrup A, Magkos F, Bier DM, Brenna JT, de Oliveira Otto MC, Hill JO, King JC, Mente A, Ordovas JM, Volek JS, Yusuf S, Krauss RM. Saturated fats and health: A reassessment and proposal for food-based recommendations: JACC State-of-the-Art review. J Am Coll Cardiol. 2020;76(7):844-857. DOI: 10.1016/j.jacc.2020.05.077 2. Bojková B, Winklewski PJ, Wszedybyl-Winlewska M. Dietary fat and cancer-Which is good, which is bad, and the body of evidence. Int J Mol Sci. 2020;21(11):4114. DOI: 10.3390/ijms21114114 3. Custers, Emma EM, Kiliaan, Amanda J. Dietary lipids from body to brain. Prog Lipid Res. 2022;85:101144. DOI: 10.1016/j.plipres.2021.101144 4. de Souza RJ, Mente A, Maroleanu A, Cozma AI, Ha V, Kishibe T, Uleryk E, Budylowski P, Schünemann H, Beyene J, Anand SS. 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