"The cell never acts; it reacts." - Ernst Haeckel
Introduction | Glycation | Oxidative Stress | Mitochondrial Dysfunction | Insulin Resistance | Membrane Instability | Chronic Inflammation | Impaired Methylation | Autophagy Dysregulation | Final Thoughts | Takeaway Points | References | Disclaimer
Introduction
Chronic diseases develop as a result of eight cellular processes being metabolically compromised. The mechanisms linked to the metabolic syndrome and the diseases that result from it include glycation, oxidative stress, mitochondrial dysfunction, insulin resistance, cell membrane instability, chronic inflammation, impaired methylation, and autophagy dysregulation. In principle, the strategies that treat the pathologies resulting from these cellular processes are fairly straightforward. They include a nutrient-dense diet, quality sleep, regular exercise, intermittent fasting, and reducing stress, smoking, and alcohol consumption. However, our current state of health, the number of problems we need to address and their complexity, as well as our determination, all regulate the recovery process and its speed. The choices, habits, and patterns we make every day affect our health and are a good way to predict illness.
Glycation
The process
Glycation, also called "the browning effect," is a process in which sugars like glucose and fructose bond to nucleic acids, lipids, and proteins without the help of enzymes [the Maillard reaction]. These non-enzymatic formations are spontaneous and "impact stability and metabolic network structure" as well as cellular physiology[1]. Glycation initiates the formation of glycotoxins, also called advanced glycation end products [AGEs] in the bloodstream. AGEs are considered biomarkers of many degenerative diseases, such as Alzheimer's disease, diabetes, cardiovascular disease, and atherosclerosis. They are also a marker of rapid aging. Glycation in humans can occur either in vivo [inside our bodies] or we can get exposed to AGEs through the diet. Frying, roasting, and grilling foods at high temperatures gives them the browning effect and encourages the creation of carboxymethyl lysines [CMLs], a type of AGE.
How it affects the human body
The Maillard reaction causes the formation of AGEs, flavors, and colors in food. It takes place during food preparation, food storage, cigarette smoking, and in the human body. The dietary accumulation of AGEs within our systems is associated with[2]:
increased inflammatory response,
oxidative stress,
impaired endothelial function,
insulin resistance,
AGE-related LDL production and total cholesterol,
elevated markers of cardiovascular disease,
modifications to the gut microbiome,
the impairment of motor functions in the elderly.
Advanced glycation end products are linked to the development of heart disease, kidney disease, the metabolic syndrome, type 2 diabetes, and age-related cognitive and motor dysfunctions. This is because AGEs build up in the body over the course of a person's life and have harmful effects on the body.
How to fix it
Our bodies are naturally equipped with mechanisms that aid in the elimination of AGEs. The deglycation processes include enzymatic degradation, renal clearance, metal redox chelation, and the metabolism performed by gut microbes, to mention just a few. However, they are effective in a healthy body. If a person has a health condition such as chronic kidney disease or type 2 diabetes, they must modify their cooking habits to reduce the amount of AGEs they consume. It is recommended that stewing, cooking at a low temperature, and steaming foods, especially meats, reduce AGE levels. Products such as fish, legumes, vegetables, fruits, and whole grains are also low in AGEs. Furthermore, a Mediterranean diet enriched with curcumin, a potent anti-inflammatory agent, was found to be successful in reducing circulating AGEs in the body[3]. Another important step in avoiding excess glycotoxins is reducing or even cutting out the sugar that is added to processed foods and pre-made products. Meat marinades, sweet baked goods, candy, sauces, and other sugar-containing ingredients that go through high-temperature processing result in the formation of bonds between sugar molecules and fat and protein molecules, aka AGEs. On the other hand, marinating meat in acidic substances such as lemon juice or vinegar for 1 hour prior to cooking diminishes the production of glycotoxins[4].
Lastly, supplements that reduce inflammation, help fight oxidative stress, and promote a healthy gut microbiome could be of great help.
"The reduction in AGE level can be achieved by [...] supplementing the diet with α-lipoic acid, vitamin A, and L-carnitine, with exercise also playing a significant role in the process," according to studies[3].
As always, the implementation of any supplement into one's diet needs to be discussed with a trained health professional.
Oxidative stress and chronic diseases
The process
Oxidative stress is a process of tissue damage that takes place when our bodies produce more reactive oxygen species [free radicals] and too few antioxidants to combat these damaging molecules. Free radicals are by-products of oxygen metabolism, and they are naturally present in low numbers within the cells of the human body. They are produced by the cell mitochondria. They become harmful, however, when their production increases and the balance with antioxidants is shaken. The most common forms of reactive oxygen species [ROS] are superoxide radicals, hydrogen peroxide, hydroxyl radicals, and singlet oxygen[5]. Oxidative stress is linked with a wide variety of diseases, and it can either contribute to or trigger our health problems.
How it affects the human body
"Oxidative stress is [...] useful in some instances. For example, [it] induces apoptosis to prepare the birth canal for delivery. Also, biological defense mechanisms are strengthened by oxidative stress during appropriate physical exercise and ischemia"[6].
These processes, however, are natural occurrences that our bodies are equipped to handle correctly. Oxidative stress that harms our bodies is induced mostly by our lifestyle choices, which include smoking, drinking alcohol, stress, and diet[6]. The detrimental health effects that oxidative stress causes are:
damage to cell membranes, proteins, lipids, lipoproteins [molecules made from proteins and lipids], and DNA,
influences epigenetic information,
induces carcinogenesis and chronic and degenerative diseases such as cardiovascular, kidney, neurological, and respiratory conditions, and rheumatoid arthritis.
late puberty onset,
accelerates the aging process.
How to fix it
Addressing our lifestyle choices is a key element in reducing oxidative stress. Adopting a healthy, nutrient-dense diet, getting a sufficient amount of sleep every night, reducing stress, and quitting smoking and excessive drinking will help induce positive changes in the functioning of our bodies. Additionally, antioxidant substances obtained either from diet or supplementation can further improve the level of oxidative stress. Vitamin E, flavonoids [e.g., genistein], vitamin C, and polyphenols [e.g., esculetin, anthocyanins, curcumin[5] have free radical scavenging properties and diminish the damage caused by ROS.
Mitochondrial dysfunction
The process
Mitochondrial dysfunction refers to the improper functioning of mitochondria in our cells. It is caused by an impaired synthesis of ATP [adenosine triphosphate] molecules, an insufficient number of mitochondria, or an impaired supply of substrates that serve this organelle[7]. Mitochondria are responsible for maintaining cellular metabolism, cellular signaling, and the production of cellular ATP. The dysfunctions result in cell damage and membrane permeability, apoptosis [cell death], mitochondrial DNA damage, and shortened mitochondrial life. They lead to such health outcomes as poor insulin control in obesity, the development and progression of cancer, and cardiovascular diseases, including atherosclerosis.
How it affects the human body
The term "mitochondrial dysfunction" is now widely used to describe a wide range of metabolic, cardiovascular, neurodegenerative, and neuromuscular disorders, all of which are thought to result from a complex interaction of multiple genes [polygenic conditions]. At first, the term "mitochondrial dysfunction" only applied to conditions caused by changes in a single gene [monogenic conditions].
Health conditions influenced or caused by defects in the mitochondria include:
Neurodegenerative diseases such as Parkinson's, Alzheimer's, and Huntington's diseases, Friedreich's ataxia, infantile mtDNA depletion syndrome, ophthalmoplegia, male subfertility, and potentially premature senescence[8],
Cardiovascular diseases such as heart failure[9] and atherosclerosis[10],
Type 2 diabetes and insulin insensitivity[11],
Cancer[12].
Early aging, amyotrophic lateral sclerosis [ALS], autism, chronic fatigue syndrome, and migraine headache[13].
How to fix it
Inadequate nutrition, environmental toxins, and oxidative stress[13] can all cause significant damage to the mitochondria. The essential nutrients that aid ATP production include CoQ10, carnitine, iron, magnesium, manganese, B1 [thiamin], B2 [riboflavin], B3 [niacin], and cysteine [glutathione]. Furthermore, the detoxification of heavy metals, reducing the exposure to persistent organic pollutants [POPs], prescription drugs [Acetaminophen, Antibiotics, Aspirin, AZT, Cocaine, Grisepfulvin, Indomethacin, Methamphetamine, l-DOPA, NSAIDs, and Statins], diminished alcohol consumption, and the implementation of strength training will improve mitochondrial function.
Insulin resistance
The process
Insulin resistance is a dysfunction of insulin action. Elevated blood levels of glucose and lipids [fats], chronic inflammation, mitochondrial dysfunction, and impaired endoplasmic reticulum function—a functional component of a cell that produces proteins—are the causes of it. Insulin resistance induces hyperinsulinemia and hyperglycemia. Both of these conditions are triggering factors for such metabolic diseases as type 2 diabetes, hypertension, kidney disease, and cardiovascular disease[14].
How it affects the human body
Insulin resistance has many negative effects on our metabolism. Impaired insulin action is linked with such conditions as[17]:
hyperglycemia,
hypertension,
dyslipidemia,
visceral adiposity,
hyperuricemia,
elevated inflammatory markers,
endothelial dysfunction,
prothrombic state.
The development of these health issues may lead to the development of prediabetes and later type 2 diabetes. They can also result in obesity, polycistic ovary syndrome [PCOS], non-alcoholic fatty liver disease, and cardiovascular disease.
How to fix it
Overeating, a diet rich in trans-fats, carbohydrates, sugar, alcohol, and processed foods, and the consumption of products scoring highly in the glycemic index [GI] all contribute to insulin resistance[15]. Adjusting the diet to promote healthy digestion, whole food consumption, and a high fiber content is a key element of managing insulin resistance. Additionally, intermittent fasting[16] is also a proven tool that helps improve poor glucose control. Furthermore, nutrients such as zinc, chromium, and iron have been shown to positively influence various mechanisms related to insulin activity. Lastly, physical exercise, stress reduction, and sufficient restful sleep further contribute to normalizing insulin action in the body.
Membrane instability
The process
Membrane instability is a process where the integrity of the cell's outer layers [membranes] is harmed, making them unable to maintain the internal homeostasis that encourages proper cellular functioning. Membrane instability affects how cells send and receive signals inside and outside the cell. It can also cause oxidative damage, osmotic stress, and even cell death[18]. The damage to the outer membranes of the cells can be either mechanical or biochemical.
How it affects the human body
Cell membrane instability, injury, and permeability contribute to a wide variety of pathological changes within the organism[18]. Leaky cell membranes are linked with the following health conditions:
impaired calcium homeostasis causes muscle weakness, atrophy, and muscle degeneration,
genetic muscle diseases such as Duchenne muscle disease, Becker muscle disease, Tibial muscle disease, Limb-Girdle muscle disease, Miyoshi myopathy, and Niemman-Pick disease,
cardiovascular diseases such as myocardial infarction,
increased susceptibility to pneumonia, meningitis, and septicaemia,
age-related neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease,
obesity and metabolic syndrome.
How to fix it
The cells in our bodies are naturally equipped with repair mechanisms that help them rebuild and restore their functions. It also applies to their membranes. Cell membranes can repair dysfunctional and injured elements to maintain their integrity under favorable conditions. However, there are factors that may make this process very hard. Poor diet, obesity, an inactive lifestyle, and medications are the key elements that contribute to the membrane's ill health. Regular exercise, the maintenance of a healthy weight, a nutrient-dense whole-food diet, proper sleep, and possibly the reduction of prescription drug usage will improve the functioning of the cells in our bodies and create space for them to heal. It was observed that a diet rich in polyunsaturated fatty acids [PUFAs], such as Omega-3s, has a beneficial effect on cell membranes since fatty acids are a building block of the cell[19].
Chronic inflammation
The process
Chronic inflammation takes place when the body's response to an inflammatory stimulus lasts for a long time. This causes immune tolerance to break down. The persistent inflammatory response and the ongoing involvement of lymphocytes and macrophages result in tissue damage, which is its defining feature. This leads to functional tissue impairment throughout the whole body[20]. Chronic inflammation can be caused by continuous infections [pathogens, bacteria, and viruses], the presence of toxic agents [crystalline silica, heavy metals, and toxins], persistant stress, or autoimmunity. Furthermore, it is linked to the development and progression of a wide range of long-term diseases, such as autoimmune conditions, metabolic disorders, fibrosis, and even cancer.
How it affects the human body
Chronic inflammation damages the cells, tissues, and organs of the body. It can also lead to DNA impariments[21]. Such a wide, harmful effect on the human organism creates a favorable environment for a disease to develop. Chronic inflammation is an underlying cause of:
cardiovascular disease,
chronic kidney disease,
irritable bowel disease [IBD],
cancer,
rheumatoid arthritis,
diabetes,
Alzheimer's disease,
allergic asthma,
chronic obstructive pulmonary disease [COPD].
How to fix it
Lifestyle changes—dropping bad habits and adopting new, healthy ones—will greatly improve the inflammatory changes in the human body. Quitting smoking, reducing alcohol consumption, improving sleep quality, following a whole-foods-based, fiber-rich, low-glycemic diet, avoiding trans fats, participating in regular exercise, and practicing intermittent fasting all promote health and reduce inflammation. Furthermore, nutrients such as omega-3 fatty acids [fish or algae oil], curcumin, magnesium, vitamin D, vitamin E, zinc, selenium, and others are potent anti-inflammatory agents.
Impaired methylation
The process
Methylation is a biochemical process that attaches a methyl group, which is made up of one carbon and three hydrogen atoms, to another molecule, like DNA, RNA, or a protein[22]. The addition of a methyl group can change the function of another molecule in the body. In the case of a DNA sequence, the addition of a methyl group may influence gene expression and therefore turn the gene on or off. Such changes in molecular function may increase the risk of disease development.
How it affects the human body
Lifestyle factors have an impact on methylation. Smoking, binge drinking, and other social factors, such as one's socioeconomic status or demographic background, affect gene expression in our bodies. DNA and protein methylation are associated with:
DNA methylation is linked with cervical and breast cancers,
RNA methylation is linked with liver, colon, and other gastric types of cancer,
Protein methylation: lysine methylation linked with pancreatic cancer; arginine methylation linked with oesophageal cancer,
Air-pollution-induced DNA methylation is linked with pulmonary diseases such as lung disease, a slower fetal growth rate in the uterus, and reduced immune function[23],
Prenatal maternal stress-induced DNA methylation impacts placenta function[24],
Parental maltreatment of children and stress-induced methylation are linked with depression in those children[24],
Tabacco smoking-induced DNA methylation is linked with all-cause, cardiovascular, cancer, and other mortality[25].
How to fix it
Elevated levels of homocysteine in the blood are a hallmark of many diseases brought on by the methylation process. Homocysteine inhibits DNA synthesis and induces hypomethylation, causing damage to various cells and provoking disease. Lowering homocysteine levels to prevent illness is an essential step. It can be achieved by supplementing with vitamins B12, B6, and folate. Furthermore, environmental and lifestyle changes can also help diminish the negative effects of methylation on our bodies. Regular exercise and supplementation with B vitamins, antioxidants, and carotenoids can help reduce air pollution-induced methylation[23]. Quitting smoking, getting a lot of fresh air, reducing alcohol consumption, getting a sufficient amount of sleep, and reducing stress all contribute to health and inhibit methylation processes.
Autophagy dysregulation
The process
Autophagy is a "housekeeping" process in our bodies by which old, damaged proteins, cell organelles, and intracellular pathogens are eliminated and recycled to aid important cell functions[26]. Autophagy also aids in the clearance of invading bacteria and viruses, as well as the prevention of tumor cell formation. Dysregulation of autophagy in our bodies can be induced by overeating, which causes an energy imbalance.
How it affects the human body
Autophagy helps maintain energy homeostasis in the body. Furthermore, it is responsible for regulating lipid, amino acid, and glucose metabolism[27]. Alternations to these processes cause dysregulation in autophagy and result in the occurrence of health conditions such as:
obesity,
insulin resistance,
type 2 diabetes,
atherosclerosis,
inflammation,
infertility,
osteoporosis,
cancer,
cognitive aging, dementia, neurodegenerative diseases: Alzheimer's disease, Parkinson's disease, Huntington's disease,
skeletal muscle diseases: duchenne muscular dystrophy, Ullrich muscular dystrophies and bethlem myopathy, Danon disease, Pompe disease, etc.[28]
How to fix it
Autophagy is induced by lifestyle interventions such as exercise, calorie restriction, a ketogenic diet, intermittent fasting, quality sleep, and hot and cold exposure. In addition, a nutrient-dense, whole-foods-based diet rich in polyphenols [plant compounds] also induces this healthful process. Polephenol-rich foods include green tea, grape skin (red wine), nuts, onions, apples, berries, turmeric, soybeans, and milk thistle[29].
Final Thoughts
The way our bodies function is reflected in our health. If the mechanisms that govern the key metabolic processes are disrupted and far from efficient, they will provide space for the emergence of a wide variety of health conditions. It quickly becomes clear that lifestyle changes can help and have an impact on the majority of these health issues if we try to find the commonalities among them all. Health depends on our daily choices. It requires proper nutrition, regular physical activity, a good night's rest, stress reduction, quitting smoking, and avoiding excessive alcohol consumption. Being mindful of how we carry ourselves and understanding that our habits and choices impact the above-mentioned metabolic processes should be motivation enough to start living our best lives. It is important to mention, though, that restoring our health to its homeostatic baseline is a great effort. Depending on how advanced our health problems are, they will require dedication, focus, determination, and, very often, professional help, either from a medical practitioner, a nutritionist, or a health coach, to reduce their impact on our bodies.
Takeaway Points
Our health is decided on a cellular level.
Diseases have been linked to glycation, oxidative stress, mitochondrial dysfunction, insulin resistance, unstable cell membranes, chronic inflammation, poor methylation, and autophagy dysregulation.
Adjusting our lifestyle can greatly improve our health.
Proper nutrition, regular physical activity, a good night's sleep, reducing stress, quitting smoking, and not drinking too much alcohol are all good ways to elevate our health.
Supplements can help fix some of the problems that come up when these metabolic processes don't work right.
References
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