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What Is Epigenetics ?

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Epigenetics involves genetic control by factors other than an individual's DNA sequence. Epigenetic changes can switch genes on or off and determine which proteins are transcribed.

Epigenetics involves genetic control by factors other than an individual’s DNA sequence. Epigenetic changes can switch genes on or off and determine which proteins are transcribed.
Epigenetics is involved in many normal cellular processes. Consider the fact that our cells all have the same DNA, but our bodies contain many different types of cells: neurons, liver cells, pancreatic cells, inflammatory cells, and others. How can this be? In short, cells, tissues, and organs differ because they have certain sets of genes that are “turned on” or expressed, as well as other sets that are “turned off” or inhibited. Epigenetic silencing is one way to turn genes off, and it can contribute to differential expression. (D. Simmons,2008). Increasing evidence shows that environmental and lifestyle factors (such as nutrition, behavior, stress, physical activity, working habits, smoking and alcohol consumption) may influence epigenetic mechanisms. Within cells, there are three systems that can interact with each other to silence genes: DNA methylation, histone modifications, and RNA-associated silencing. (Figure 1)

Figure 1. Epigenetic systems, https://www.labclinics.com/2018/11/08/role-dna-methylation-disease/?lang=en.

DNA Methylation
DNA methylation is a chemical process that adds a methyl group to DNA. It is highly specific and always happens in a region in which a cytosine nucleotide is located next to a guanine nucleotide that is linked by a phosphate; this is called a CpG site (Egger et al., 2004; Jones & Baylin, 2002; Robertson, 2002). CpG sites are methylated by one of three enzymes called DNA methyltransferases (DNMTs) (Egger et al., 2004; Robertson, 2002). Inserting methyl groups changes the appearance and structure of DNA, modifying a gene’s interactions with the machinery within a cell’s nucleus that is needed for transcription.
Histone Modifications
Histones are proteins that are the primary components of chromatin, which is the complex of DNA and proteins that makes up chromosomes. Histones act as a spool around which DNA can wind. When histones are modified after they are translated into protein (i.e., post-translation modification), they can influence how chromatin is arranged, which, in turn, can determine whether the associated chromosomal DNA will be transcribed. If chromatin is not in a compact form, it is active, and the associated DNA can be transcribed. Conversely, if chromatin is condensed (creating a complex called heterochromatin), then it is inactive, and DNA transcription does not occur.
There are two main ways histones can be modified: acetylation and methylation. These are chemical processes that add either an acetyl or methyl group, respectively, to the amino acid lysine that is located in the histone. Acetylation is usually associated with active chromatin, while deacetylation is generally associated with heterochromatin. (D.Simmons et.al, 2008). Histone acetylation is modulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). (Guo Li et. al, 2020). On the other hand, histone methylation can be a marker for both active and inactive regions of chromatin. For example, methylation of a particular lysine (K9) on a specific histone that marks silent DNA is widely distributed throughout heterochromatin. In contrast, methylation of a different lysine (K4) on the same histone is a marker for active genes (Egger et al., 2004).
RNA-Associated Silencing
Genes can also be turned off by RNA when it is in the form of antisense transcripts, noncoding RNAs, or RNA interference. RNA might affect gene expression by causing heterochromatin (i.e. tightly packed form of DNA) to form, or by triggering histone modifications and DNA methylation (Egger et al., 2004).
Epigenetics and Disease
While epigenetic changes are required for normal development and health, they can also be responsible for some disease states. Disrupting any of the three systems that contribute to epigenetic alterations can cause abnormal activation or silencing of genes. Such disruptions have been associated with cancer, syndromes involving chromosomal instabilities, and mental retardation. For example, researchers found that diseased tissue from patients with colorectal cancer had less DNA methylation than normal tissue from the same patients (Feinberg & Vogelstein, 1983). Because methylated genes are typically turned off, loss of DNA methylation can cause abnormally high gene activation by altering the arrangement of chromatin. On the other hand, too much methylation can undo the work of protective tumor suppressor genes. (Figure 2).

Figure 2. Schematic outline of the most relevant DNA methylation changes observed in human cancers. These events include CpG-island-specific DNA hypermethylation often occurring at gene promoters, which locks the affected gene into an inactive state. Loss of DNA methylation (hypomethylation) occurs genome-wide and is often observed at repetitive regions of the genome. White circles indicate unmethylated CpG sites and red circles show methylated CpG sites. The crossed-out arrow indicates the transcription start site and the permanent lack of transcription after DNA methylation. Green boxes show exons and the blue rectangle marks the position of a repetitive element. (Gerd Pfeifer, 2018)
Combating Diseases with Epigenetic Therapy
Because so many diseases involve epigenetic changes, it seems reasonable to try to counteract these modifications with epigenetic treatments. These changes seem an ideal target because they are by nature reversible, unlike DNA sequence mutations. The most popular of these treatments aim to alter either DNA methylation or histone acetylation.
Inhibitors of DNA methylation can reactivate genes that have been silenced. Two examples of these types of drugs are 5-azacytidine and 5-aza-2′-deoxycytidine (Egger et al., 2004). Drugs aimed at histone modifications are called histone deacetylase (HDAC) inhibitors. HDACs are enzymes that remove the acetyl groups from DNA, which condenses chromatin and stops transcription. Blocking this process with HDAC inhibitors turns on gene expression. (Egger et al., 2004).
Caution in using epigenetic therapy is necessary because epigenetic processes and changes are so widespread. To be successful, epigenetic treatments must be selective to irregular cells; otherwise, activating gene transcription in normal cells could make them cancerous, so the treatments could cause the very disorders they are trying to counteract. Despite this possible drawback, researchers are finding ways to specifically target abnormal cells with minimal damage to normal cells, and epigenetic therapy is beginning to look increasingly promising. (D. Simmons, 2008)
Natural compounds and epigenetics
Natural products are regaining attention as sources of lead compounds that can be used as a starting point of drug or epigenetic probe discovery. https://www.frontiersin.org/articles/10.3389/fphar.2021.651395/full
Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines.


The compound (–)-epigallocatechin-3-gallate (EGCG) is the major catechin found in green tea [Camellia sinensis L. Ktze. (Theaceae)].
Psammaplins from the Sponge Pseudoceratina purpurea: Inhibition of Both Histone Deacetylase and DNA Methyltransferase (https://pubs.acs.org/doi/10.1021/jo034248t)
More recently, some natural compounds have been reported as efficient against DNMTs activity; specifically, in the aforementioned review, the authors extensively describe the activity of (–)-epigallocatechin-3-gallate, contained in green tea, polyphenol curcumin, the flavonoid quercetin, kazinol Q, resveratrol (3, 4′, 5-trihydroxystilbene), the quinone Nanaomycin A, the isoflavone genistein, the isothiocyanate sulforaphane, the pentacyclic terpenoid Boswellic acid, the Z-ligustilide, the germacrane sesquiterpene lactone parthenolide and the ubiquinone derivative Antroquinonol D.
Specifically, the distinct HDAC inhibitors differ between zinc-binding inhibitors (linear HDAC inhibitors, cyclic tetrapeptides, cyclic depsipeptides) and non-zinc-binding inhibitors (e.g., Ursolic acid, Epicocconigrones A and B, Curcumin, n-Butyric acid and Aceroside VIII).


What are polyphenols ?

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In addition to nutrients that are found in fruits and vegetables, such as essential vitamins and minerals, there are a number of plant-derived components- phytochemicals, that could promote health.

These plant-derived components include fiber, carotenoids, phytosterols and substantial class of these are phytochemicals called polyphenols. [1]. The chief reason for this interest is the recognition of the antioxidant properties of polyphenols, their great abundance in our diet, and their probable role in the prevention of various diseases associated with oxidative stress, such as cancer and cardiovascular and neurodegenerative diseases [1], and also  diabetes, and chronic respiratory diseases.[2] Furthermore, polyphenols, which constitute the active substances found in many medicinal plants, modulate the activity of a wide range of enzymes and cell receptors. In this way, in addition to having antioxidant properties, polyphenols have several other specific biological actions that are yet poorly understood.

Classes and sources

The polyphenols constitute a large group of bioactive phytochemicals that include multiple sub-classes such as:



Phenolic acids


One of the most studied groups of polyphenols is the flavonoids, which can be sub-divided into groups, including: flavan-3-ols, flavonols, flavones, isoflavones, flavanones, and anthocyanins. Specific examples of these natural polyphenols and some known food sources for each class are shown in Table 1.

Table 1 Food sources of major polyphenol classes [1]

Polyphenol class

Food sources


Black tea, green tea, red wine, white wine, walnuts, almonds, apple with peel, blueberries, oranges, dark chocolate, raw spinach, onion, Brassicaceae products (e.g. kale, broccoli)


Black tea, green tea, red wine, almonds, hazelnuts, apple with peel, blueberries, dark chocolate


Citrus fruits and juices, tomatoes and tomato-derived products


Grain mixtures, vegetable oils, celery, sweet pepper


Soy, tofu, legumes


Red wine, blueberries, other berries, pomegranate, blue corn


Grape seed, red wine, bilberry, cranberry, black currant, green tea, black tea, cocoa, peanuts, pine bark


Coffee, yerba mate, red wine, red fruits, vegetables, whole grains



Ellagic acid and ellagitannins

Berries, tropical fruits, pomegranates, nuts


Whole bran cereals, flaxseed


Red wine, grapes

Phenolic acids

Berries, spices, cereals, tea


Tonka beans, cinnamon

Health benefits

The primary mechanism of action of polyphenols was originally thought to lie in their direct antioxidant effects. [1]. However, these effects are no longer considered to be enough explanation of multiple benefits on human health. A number of other possible biochemical and molecular mechanisms have been identified, including multifarious effects within intra- and inter-cellular signalling pathways, such as regulating nuclear transcription factors and fat metabolism, and modulating the synthesis of various inflammatory mediators.

Polyphenols from various food sources have been associated with various health-related benefits, including in cardiovascular disease, type 2 diabetes, obesity, inflammation, cancer.

Type 2 diabetes. Researchers have reported that polyphenols may lower the risk for type 2 diabetes by boosting insulin sensitivity, slowing down the rate the body digests and absorbing sugar. For example, a type of flavonoid called flavan-3-ols may be especially beneficial for lowering insulin resistance.[3].

Inflammation. Animal studies show positive results of polyphenols on inflamation biomarkers. In a study of adults researchers found that higher levels of lignans in the urine were associated with lower levels of measures of inflammation. This could be important since long-term inflammation has been associated with certain diseases, such as heart disease and cancer.

Cardiovascular disease. Researchers have found, that polyphenols from various food sources such as cocoa, coffee, tea, and apples have been associated with various health-related benefits, including in cardiovascular disease and type 2 diabetes. Possible mechanisms include effects on blood pressure, endothelial function, glucose metabolism, inflammation, oxidative stress biomarkers, platelet function, and cholesterol, as well as indirect effects mediated by interaction with the gut microbiome.[1]

Obesity. Polyphenol intake may also play a role in body weight regulation. Researchers found that a higher flavonoid intake is associated with lower body mass index and waist circumference.[3]

Cancer. Research consistently links diets rich in plant foods to a lower risk of cancer, and many experts believe that polyphenols are partly responsible for this. Polyphenols have strong antioxidant and anti-inflammatory effects, both of which can be beneficial for cancer prevention. A recent review of test-tube studies suggests that polyphenols may block the growth and development of various cancer cells. In humans, some studies link high blood markers of polyphenol intake to a lower risk of breast and prostate cancers.[4].

Polyphenols may help lower your blood sugar levels, promote healthy digestion, promote brain function (beneficial effects on cognitive functioning, memory)[1], prevent from blood clots [4]

Polyphenols may even influence gut bacteria, they can modulate the composition of an individual’s microbiome. There is a bi-directional relationship between polyphenols and the microbiome of the human gut. Also some polyphenols, such as those found in green and black tea, can inhibit the growth of detrimental bacteria such as Helicobacter pylori, Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, Listeria monocytogenes, and Pseudomonas aeruginosa, as well as hepatitis C virus, influenza, HIV, and Candida. Other polyphenols, in contrast, can stimulate growth of beneficial bacteria including Bifidobacterium spp., Lactobacillus spp., Akkermansia muciniphila, and etc. Since dysbiosis of gut microbiota has also been associated with the development of a number of diseases, including cardiovascular disease, obesity, and neurodegenerative diseases, a positive interaction with polyphenolic compounds has the potential to produce health benefits.[1]

  1. https://pubs.rsc.org/en/content/articlelanding/2019/FO/C8FO01997E
  2. https://academic.oup.com/ajcn/article/79/5/727/4690182#fn-1
  3. https://www.medicalnewstoday.com/articles/319728#possible-health-benefits-and-evidence
  4. https://www.healthline.com/nutrition/polyphenols#benefits



Resveratrol is a type of polyphenols, principally found in grapes, red wine, and berries. Resveratrol is known as a compound responsible for antioxidant and anti-inflammatory action. Resveratrol  activates sirtuins, which have been associated with a delay of aging. Controlled trials reported resveratrol’s supplementation significant impact on factors associated with diseases like type 2 diabetes, cardiovascular disease, non-alcoholic fatty liver disease: glucose control, insulin sensitivity, improved peripheral blood flow, blood pressure, total cholesterol and reduced inflammatory biomarker. https://pubs.rsc.org/en/content/articlelanding/2019/FO/C8FO01997E. Resveratrol exerts immune-regulatory effects. (https://pubmed.ncbi.nlm.nih.gov/31035454/). Also this compound has properties, including activity against neurodegeneration, several types of cancer,( https://pubmed.ncbi.nlm.nih.gov/30816367/) metabolic syndrome (https://pubmed.ncbi.nlm.nih.gov/30695995/).


Quercetin is a flavonol, found in many plants and foods, such as red wine, onions, green tea, apples, and berries. Its powerful antioxidant and anti-inflammatory activities are well documented and are thought to play a role in treating and protecting against diseases including diabetes, cancer, neurodegenerative and cardiovascular diseases. Quercetin control whole-body glucose homeostasis, that supports its possibility act as antidiabetic agent. (https://pubmed.ncbi.nlm.nih.gov/27633685/). Controlled trials confirmed, that quercetin may improve endothelial functioning, reduce blood pressure and LDL cholesterol- factors associated with cardiovascular disease. (https://pubs.rsc.org/en/content/articlelanding/2019/FO/C8FO01997E ). Quercetin has an anticancer properties. The anti-cancer effects of quercetin include its ability to promote the loss of cancer cell viability and death.  (https://pubmed.ncbi.nlm.nih.gov/31261749/)


Bromelain is a enzyme found in pineapple plants, having multiple activities in many areas of medicine. Studies reports the possible application of bromelain in treating cardiovascular diseases, blood coagulation and fibrinolysis disorders, infectious diseases, inflammation-associated diseases, and many types of cancer. Studies have shown that bromelain exhibited antibacterial, anthelmintic, antifungal activity. Bromelain able to increase antibiotics effectiveness in many disease states, e.g., sinusitis, bronchitis, pneumonia, pyelonephritis, thrombophlebitis, obsesses, cutaneous infections. Due to the good anti-inflammatory properties, bromelain is supposed to be an agent for treating chronic inflammatory bowel disease. Considerable evidence suggests that bromelain has a potential anticancer activity. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8709142/)


Curcumin is one of curcuminoids, bioactive polyphenolic compound, identified in turmeric. Curcumin is supposed to have therapeutic potential as anti-inflammatory, anti-diabetic, anti-cancer, antibiotic, and anti-aging agent, what is supported by several in vitro, in vivo, and clinical trials. In addition, curcumin has also shown promise in treating wound healing, arthritis, Alzheimer’s, inflammatory bowel diseases (IBD), cardiovascular disease, myocardial infarction, and atherosclerosis. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6720683/). Curcumin has been shown to target multiple signalling molecules while also demonstrating activity at the cellular level. It has been shown to benefit inflammatory conditions, metabolic syndrome, pain, and inflammatory and degenerative eye conditions. Curcumin has been shown to attenuate several aspects of metabolic syndrome by improving insulin sensitivity, suppressing adipogenesis, and reducing elevated blood pressure, inflammation, and oxidative stress. In addition, it has been shown to benefit the kidneys. Most of these benefits are attributed to curcumin’s antioxidant and anti-inflammatory effects. ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664031/)


Berberine, an alkaloid class bioactive compound, isolated from the Chinese herb Coptis chinensis and other Berberis plants. Berberine has a wide range of pharmacological properties and can be used to treat many diseases, such as cancer and digestive, metabolic, cardiovascular, and neurological diseases. It can inhibit toxins and bacteria, including Helicobacter pylori (https://link.springer.com/article/10.1007/s11684-019-0724-6 ), also fungus, parasites, viruses. (https://naturopathic.org/news/565580/6-Potential-Benefits-of-Berberine-You-Should-Know-About.htm). Berberine also inhibits the proliferation of various types of cancer cells and impedes invasion and metastasis. Berberine regulates glucose and lipid metabolism, improves energy expenditure, reduces body weight, and alleviates non-alcoholic fatty liver disease. (https://link.springer.com/article/10.1007/s11684-019-0724-6 ). Many studies show that berberine can significantly reduce blood sugar levels in individuals with type 2 diabetes (https://www.healthline.com/nutrition/berberine-powerful-supplement#TOC_TITLE_HDR_4) and effectiveness of berberine is comparable to the popular diabetes drug metformin. Also berberine can help improve cholesterol and triglycerides measures. ( https://www.healthline.com/nutrition/berberine-powerful-supplement#TOC_TITLE_HDR_6). Berberine have benefits on cardiovascular function, improves blood circulation and pressure, suppresses ischemic arrhythmias, attenuates the development of atherosclerosis, and reduces hypertension. Berberine shows potent neuroprotective effects. Berberine might help women avoid the pain and burning of recurring urinary tract infections (UTIs) and bladder inflammation known as cystitis. ( https://naturopathic.org/news/565580/6-Potential-Benefits-of-Berberine-You-Should-Know-About.htm)

Beta- Glucan

Beta-glucan is a polysaccharide, soluble fibber, found naturally in cereal grains, yeast, and certain mushrooms. As a soluble fibber, beta-glucan itself is not digested, but it does slow food transit in the intestines. Beta-glucan offer a number of health benefits, including lowering cholesterol (especially LDL), improving blood sugar management, and have proven antitumor, anti-microbial, anti-allergic, and immune-modulating effects. (https://www.webmd.com/diet/health-benefits-beta-glucan#1). Studies reports that oat-derived beta-glucan may significantly reduce levels of total and LDL (“bad”) cholesterol. Researchers suggests that beta-glucan may help manage diabetes by controlling blood sugar levels, lowering cholesterol, and keeping blood pressure in check. Beta- glucan can act as an immune system activator and cell response modifier. Extracted and/or purified β-glucans have been used in clinical cancer treatment. Beta glucan has demonstrated anti-osteoporotic activities in clinical trials. ( https://www.webmd.com/diet/health-benefits-beta-glucan#1). Studies have reported, that β-glucan confers protection to DNA through its antioxidant activity and by enhancing the DNA repair system. (https://www.sciencedirect.com/science/article/pii/S2405844021001080)


Pterostilbene is a natural polyphenolic compound, closely related to resveratrol, and both are known as stilbenes. Pterostilbene food sources include blueberries, other deeply hued berries such as cranberries, bilberries, lingonberries, huckleberries, and red grapes. Pterostilbene exhibits increased bioavailability, making it potentially advantageous as a therapeutic agent. Substantial evidence suggests that pterostilbene may have numerous preventive and therapeutic properties in a vast range of human diseases that include neurological, cardiovascular, metabolic, and hematologic disorders. The multiple benefits of pterostilbene have been attributed to its antioxidant, anti-inflammatory, and anticarcinogenic properties leading to improved function of normal cells and inhibition of malignant cells. Pterostilbene reduces oxidative stress downregulating production of reactive oxygen species and increasing antioxidant agents. ( https://www.mindbodygreen.com/articles/pterostilbene-what-this-potent-antioxidant-can-do-for-you). Some evidence suggests that pterostilbene and resveratrol may increase life span and help prevent age-related disorders. Studies suggests that it may be an effective anti-cancer agent based on its antineoplastic properties- the ability to prevent, inhibit, or halt the development of a tumor, Pterostilbene may help preserve cognitive function and reduce the risk of Alzheimer’s disease, in part by reducing inflammation. Pterostilbene may improve overall cardiovascular health, including regulation of blood pressure. Also, pterostilbene may help regulate blood sugar, improve insulin sensitivity, and manage diabetes. One proposed mechanism for regulating blood sugar is that pterostilbene reduces oxidative stress in the liver and kidneys. (https://www.mindbodygreen.com/articles/pterostilbene-what-this-potent-antioxidant-can-do-for-you)

N-Acetyl-l-Cysteine (NAC)

Cysteine is a semi-essential amino acid, found in high-protein foods such as beef, chicken, eggs, and whole grains. It is considered semi-essential because human’s body can produce it from other amino acids, namely methionine and serine. It becomes essential only when dietary intake of methionine and serine is low. N-acetyl cysteine (NAC) is a supplement form of cysteine. NAC bonds with some substances to form glutathione, most powerful antioxidant. So, NAC is valued primarily for its antioxidant properties, respectively, benefits on immune function, that is important in numerous ailments caused by oxidative stress, including heart disease, infertility, diabetes, and some mental health conditions. NAC plays an important role in body’s detoxification process, may prevent, or reduce kidney and liver damage. NAC also has applications for other liver diseases. NAC helps regulate levels of glutamate, which imbalance can cause some neuropsychiatric disorders. By regulating glutamate levels in the brain, NAC may alleviate symptoms of mental health conditions and reduce substance use and cravings. NAC’s antioxidant and expectorant capacity can improve lung function, including cystic fibrosis, asthma, and pulmonary fibrosis by decreasing inflammation. Researchers suggests, NAC may help improve fertility in men by reducing oxidative stress that damages or kills reproductive cells. Animal studies show that NAC may stabilize blood sugar and improving insulin resistance, that is the case in diabetes and other metabolic disorders. Also, NAC may reduce heart disease risk by reducing oxidative tissues damage in the heart and improving blood flow. (https://www.healthline.com/nutrition/nac-benefits#TOC_TITLE_HDR_5)

Diindolylmethane (DIM)

Diindolylmethane is made in the body from a chemical called indole-3-carbinol, which is found in cruciferous vegetables such as cauliflower, broccoli, Brussels sprouts. (https://www.webmd.com/vitamins/ai/ingredientmono-1049/diindolylmethane). Research suggests that DIM help balance hormone levels via its effects on estrogen. As a result, DIM supplements have been gaining popularity as a potential treatment for a variety of hormone-related conditions, like acne, menopause symptoms, prostate issues, and certain forms of cancer, including ovarian, prostate, and colon cancers.( https://www.healthline.com/nutrition/dim-supplement#uses-benefits). Studies with indole-3-carbinol and its dimeric product DIM suggest that these compounds have the ability to deregulate multiple cellular signalling pathways that are essential for tumor growth and spread. https://pubmed.ncbi.nlm.nih.gov/35582221/ So DIM is supposed to be effective cancer chemopreventive agents in pre-clinical models and show promise in clinical trials. https://pubmed.ncbi.nlm.nih.gov/34660663/. Given that estrogen plays an important role in regulating fat accumulation, DIM supplements may aid weight loss – although no human research currently supports this effect. ( https://www.healthline.com/nutrition/dim-supplement#uses-benefits)

Coenzime Q10 (CoQ10)

Coenzyme Q10 (CoQ10) or ubiquinone is known for its key role in mitochondrial bioenergetics as electron and proton carrier and participates in cellular respiration, which generates energy in the form of ATP.  Other crucial CoQ10 role is to serve as an antioxidant and protect cells from oxidative damage. These two functions constitute the basis for supporting the clinical indication of CoQ10. CoQ10 rich foods are fatty cold-water fish, meat, peanuts, pistachios, avocado. (https://www.livestrong.com/article/256149-what-foods-are-rich-in-coq10/). Many neurodegenerative disorders, diabetes, cancer, fibromyalgia, migraine, muscular and cardiovascular diseases have been associated with low CoQ10 levels. (https://pubmed.ncbi.nlm.nih.gov/24389208/).  Studies show, that CoQ10 seems to help treat heart failure by improving heart function, increasing ATP production, and limiting oxidative damage. Supplementing with CoQ10 also help prevent and treat migraines, as it increases mitochondrial function and reduces inflammation. Improving blood sugar levels, insulin sensitivity and stimulating the breakdown of fats, CoQ10 may help to manage diabetes. Considering CoQ10 properties, including that it plays a critical role in the protection of cell DNA and cell survival, both of which are strongly linked to cancer, is supposed to be beneficial in cancer prevention and recurrence. (https://www.healthline.com/nutrition/coenzyme-q10#TOC_TITLE_HDR_11). Mitochondrial dysfunction and oxidative stress can lead to the death of brain cells and neurodegenerative diseases. Supplementation of CoQ10 has been very useful to treat mitochondrial diseases. So, CoQ10 is used largely to treat various neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and additional brain disease condition like autism, multiple sclerosis, epilepsy, depression. (https://pubmed.ncbi.nlm.nih.gov/34596729/). Also, CoQ10 can reduce oxidative damage and inflammation that results in diseases of the lungs. (https://www.healthline.com/nutrition/coenzyme-q10#TOC_TITLE_HDR_11)

Omega 3

Omega-3 polyunsaturated fatty acids (PUFAs) include α-linolenic acid (ALA), stearidonic acid (SDA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). The main sources of Omega-3 are fatty fish and plants, for example, flax, chia, and canola seeds. Health benefits on cardiovascular disease, diabetes, cancer, depression and various mental illnesses, age-related cognitive decline, periodontal disease, and rheumatoid arthritis are attributed to Omega-3. However, controversies continue with respect to the effect of Omega-3 in several health issues such as stroke, heart attacks, diabetes, cancer, and visual and neurological/brain development. (https://www.annualreviews.org/doi/10.1146/annurev-food-111317-095850?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed). Some studies suggest that Omega-3 can improve risk factors for heart disease by reduction of triglycerides, blood pressure, raising “good” cholesterol (HDL), preventing blood clots ant reducing inflammation. Low omega-3 levels have been reported in people with psychiatric disorders and omega-3 supplements can reduce the frequency of mood swings and relapses in people with schizophrenia and bipolar disorder. Several studies link higher omega-3 intake to decreased age-related mental decline and a reduced risk of Alzheimer’s disease. Studies show that people who consume the most omega-3s have up to a 55% lower risk of colon cancer. Additionally, omega-3 consumption is linked to a reduced risk of prostate and breast cancer. However, not all studies give the same results. Several studies associate omega-3 consumption with a lower risk of asthma in children and young adults. Supplementing with omega-3 fatty acids effectively reduces liver fat and inflammation. Omega-3 may improve bone strength, joint health, reduce joint pain- important issues treating or reducing risk of osteoporosis and arthritis. Omega-3 fatty acids can improve insulin resistance, inflammation, and heart disease risk factors in people with metabolic syndrome. Also, some other benefits are attributed to omega-3, like keeping the skin healthy, sleep improvement, fighting autoimmune disease, eye health improvement. (https://www.healthline.com/nutrition/17-health-benefits-of-omega-3#TOC_TITLE_HDR_9)

Vitamin D

Vitamin D is a fat-soluble vitamin in a family of compounds that includes vitamins D1, D2, and D3. A body produces vitamin D naturally when it is directly exposed to sunlight, also you can get vitamin D from certain foods, like salmon, sardines, herring, canned tuna, cod liver oil egg yolk and etc. Vitamin D is essential for maintaining a healthy mineral and bone metabolism. It stimulates calcium and phosphate absorption by the intestine, regulates bone metabolism, and negatively controls parathyroid hormone (PTH) secretion, (https://pubmed.ncbi.nlm.nih.gov/23713872/), that involved in immune response, calcium, and phosphorus concentration in the blood. Vitamin D also possesses a variety of effects unrelated with mineral and bone metabolism, including the regulation of arterial blood pressure, modulation of immunological responses, regulation of insulin production, protection against certain cancers, renoprotection, and other beneficial actions. ( https://pubmed.ncbi.nlm.nih.gov/23713872/). Researchers suggests that vitamin D may play a role in: reducing the risk of multiple sclerosis, decreasing the chance of heart disease, reducing the likelihood of severe illnesses, supporting immune health- preventing infections and autoimmune diseases, such as rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease. Low levels of vitamin D are linked with all these conditions. Also, vitamin D might play an important role in regulating mood and decreasing the risk of depression. The current research does not support the idea that vitamin D would cause weight loss, but there appears to be a relationship between vitamin D and weight. (https://www.healthline.com/health/food-nutrition/benefits-vitamin-d#1.-Vitamin-D-may-fight-disease).

What are adaptogens?

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Adaptogens are substances that improve your body’s resistance to stress, caused by different types of stressors, reduce the negative effects of stress, also help to recover from illness or physical weakness and offer other benefits as well.

Adaptogens have the ability to enhance the body’s stability against physical loads without increasing oxygen consumption. The intake of adaptogens is associated not only with the body’s better ability to adapt to stress and maintain/normalize metabolic functions, but also with better mental and physical performance. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398443/)

Adaptogens are plant-based or synthetic compounds. Unlike the synthetic adaptogens, the natural are extracts with an extremely rich phytochemical composition. Their adaptogenic properties are not due to one molecule, but to the combination of different substances. The use of natural adaptogens by humans has a rich history- they have been used in recovery from illness, physical weakness, impaired mental function, and other conditions. For about 50 years, plant adaptogens have been used by professional athletes due to their high potential to increase the body’s resilience and improve physical endurance. (ttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398443/)

Plant-based adaptogens

The biological effects of plant adaptogens are related to the complex of biologically active compounds they contain. Some of the most important phytochemicals with adaptogenic properties are: triterpenoid saponins (in Panax ginseng-ginsenosides; in Eleutherococcus senticosus-eleutherosides); phytosterols and ecdysone (in Rhaponticum carthamoides); lignans (in Schisandra chinensis); alkaloids; flavonoids, vitamins, etc.( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398443/)

Some of the most used plant adaptogens are: Panax ginseng (American ginseng), Eleutherococcus senticosus (eleuthero root), Rhaponticum carthamoides (rhaponticum), Rhodiola rosea (R. rosea), Schisandra chinensis (magnolia berry), Withania somnifera (ashwagandha), Astragalus membranaceus (astragalus), Cordyceps militaris (cordyceps), Lycium barbarum (goji berry), Ocimum sanctum (tulsi / holy basil ), Curcuma longa (turmeric), Glycyrrhiza glabra (licorice root).

How adaptogens work?

Stress is a physiological condition, that is linked with the nervous, endocrine (hormones), and immune systems. Stress response process have three stages: alarm, resistance, and exhaustion.

Adaptogens increase the state of non-specific resistance in stress and decrease sensitivity to stressors, which results in stress protection, and prolong the phase of resistance (stimulatory effect). Instead of exhaustion, a higher level of equilibrium (the homeostasis) is attained the heterostasis. The higher it is, the better the adaptation to stress.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991026/

Studies have revealed that adaptogens exhibit neuroprotective, anti-fatigue, antidepressive, anxiolytic, nootropic and CNS stimulating activity. A number of clinical trials demonstrate that adaptogens exert an anti-fatigue effect that increases mental work capacity against a background of stress and fatigue. Other pharmacological properties of adaptogens: hepatoprotective, cardioprotective, gastroprotective, antioxidant, anti-atherosclerosis, anti-hyperglycemic, anti-inflammatory/allergy. All these pharmacological effects associated with stimulating and stress-protective effects in CNS and vegetative nervous systems, endocrine system, and immune system, comprising by definition the parts of neuroendocrine-immune complex – stress-system. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991026/

Adaptogens are usually used by people to:

lmprove attention;

Lower stress-induced disorders and impairments in the body;

Balance hormone levels, including cortisol (the stress hormone);

Fight fatigue that results from excessive physical or emotional stress;

Boost the immune system;

Fight the symptoms caused by elevated cortisol levels (such as anxiety, depression, fatigue, high blood pressure, insulin resistance, and obesity);

Improve the function of organs, such as the liver and adrenal glands;

Improve the function of body systems, such as the gastrointestinal system.


The beneficial stress-protective effect of adaptogens is related to the regulation of homeostasis via several mechanisms of action- hypothalamic-pituitary-adrenal (HPA) axis and the regulation of key mediators of the stress response, including cortisol and nitric oxide (NO). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991026/

It was suggested that adaptogens have not only specific therapeutic effects in some stress-induced and stress-related disorders, but will also have an impact on the quality of life of patients when implemented as adjuvants in the standard therapy of many chronic diseases and pathological conditions (e.g., post-surgery recovery, asthenia, congestive heart failure, chronic obstructive pulmonary disease). It may be suggested that adaptogens have potential use in age related disorders, such as neurodegenerative diseases, and cardiovascular diseases. Thus, elderly people may be able to maintain their health status on a normal level, improve their quality of life and may increase longevity. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991026/

Everything we need to nourish our bodies can be found in nature.

Meet the outhorr
Dwight L. McKee, MD

Dwight L. McKee, MD, is board certified in medical oncology, hematology, nutrition, and integrative and holistic medicine. Dr. McKee graduated from the M.D. – Ph.D. program at Case-Western Reserve University in Cleveland, Ohio, where he completed the first two years of medical school, as well as full graduate studies in pharmacology, and one year of research. After changing his interest from laboratory research to clinical medicine, he completed his last two years of medical school at the University of Kentucky, in Lexington, KY, where he received his M.D. degree in 1975. He completed a rotating internship at the Washington Hospital Center in and became associate medical director of Integral Health Services in Putnam, CT. – the first integrative medicine clinic on the east coast. Over the next twelve years, he studied and practiced nutritional and mind/body medicine, along with a full range of complementary medicine disciplines.

Through working with cancer patients in his practice, he became increasingly interested in cancer medicine, which led him in 1988 to return to hospital based post-graduate training in Internal Medicine at Los Angeles County Hospital, Santa Clara Valley medical center, and Stanford University. He completed a three year fellowship in Hematology and Oncology at Scripps Clinic, in La Jolla, CA, and subsequently became board certified in both disciplines. He was also a visiting scientist at The Scripps Research Institute Immunology division for 2 years, where he pursued advanced studies in immunology, and performed laboratory research in tumor immunology.

Dr. McKee has been involved in the development of integrative cancer care, working to create a synthesis between conventional cancer medicine and alternative/complementary medicine. In 2003, he became board certified in nutrition by the Certification Board for Nutrition Specialists, of the American College of Nutrition, and in 2007 he became Board Certified in Integrative and Holistic medicine through the American Board of Holistic Medicine.

Dr. McKee has been a member of the Internal Medicine staff at Scripps Clinic, and practiced medical oncology and hematology at the San Diego Cancer Center in Vista, CA. for 3 years, where he also served as medical director for the Sharp Hospice. He subsequently practiced medical oncology and hematology for 3 years in Kalispell, MT. He served as a consultant for the San Diego Cancer Research Institute from 2001 through 2010. Since Jan. 2001, he has served as Scientific Director of Life Plus International in Batesville, Arkansas. He has co-authored a text on interactions between drugs, nutrients, and botanicals, published by Elsevier Science in 2008. In 2010, he served on the expert committee for the Institute of Functional Medicine’s symposium on cancer. He is an organizer of a yearly Cancer Strategies Symposium since 2011, sponsored by the Healthy Medicine Academy, and since 2012 has edited the quarterly Cancer Strategies Journal, which highlights advances in integrative cancer care. Dr. McKee’s experience in medical research, nutritional science, immunology, chemistry, oncology, and complementary medicine make him one of the most knowledgeable researchers and clinicians worldwide.

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