Antioxidants are compounds that inhibit oxidation. Oxidation is a chemical reaction that can produce free radicals, thereby leading to chain reactions that may damage the cells of organisms. Antioxidants such as thiols or ascorbic acid (vitamin C) terminate these chain reactions. To balance the oxidative state, plants and animals maintain complex systems of overlapping antioxidants, such as glutathione and enzymes (e.g., catalase and superoxide dismutase), produced internally, or the dietary antioxidants vitamin A, vitamin C, and vitamin E.
Antioxidants neutralize free radicals produced by various environmental insults such as ultraviolet radiation, cigarette smoke and air pollutants, thereby preventing cellular damage. The role of oxidative stress and antioxidants is known in diseases like obesity, atherosclerosis, and Alzheimer’s disease. Herein we discuss the effects of oxidative stress on the skin and role of antioxidants in dermatology.
Vitamin include in Antioxidants
Some compounds contribute to antioxidant defense by chelating transition metals and preventing them from catalyzing the production of free radicals in the cell. Particularly important is the ability to sequester iron, which is the function of iron-binding proteins such as transferrin and ferritin. Selenium and zinc are commonly referred to as antioxidant nutrients, but these chemical elements have no antioxidant action themselves and are instead required for the activity of some antioxidant enzymes, as is discussed below.
|Antioxidant||Solubility||Concentration in human serum (μM)||Concentration in liver tissue (μmol/kg)|
|Ascorbic acid (vitamin C)||Water||50–60||260 (human)|
|Lipoic acid||Water||0.1–0.7||4–5 (rat)|
|Uric acid||Water||200–400||1,600 (human)|
|Carotenes||Lipid||β-carotene: 0.5–1retinol (vitamin A): 1–3||5 (human, total carotenoids)|
|α-Tocopherol (vitamin E)||Lipid||10–40||50 (human)|
|Ubiquinol (coenzyme Q)||Lipid||5||200 (human)|
- Uric acid has the highest concentration of any blood antioxidants and provides over half of the total antioxidant capacity of human serum. Uric acid’s antioxidant activities are also complex, given that it does not react with some oxidants, such as superoxide, but does act against peroxynitrite, peroxides, and hypochlorous acid.
- Concerns over elevated UA’s contribution to gout must be considered as one of many risk factors. By itself, UA-related risk of gout at high levels (415–530 μmol/L) is only 0.5% per year with an increase to 4.5% per year at UA supersaturation levels (535+ μmol/L). Many of these aforementioned studies determined UA’s antioxidant actions within normal physiological levels, and some found an antioxidant activity at levels as high as 285 μmol/L.
- Ascorbic acid or “vitamin C” is a monosaccharide oxidation-reduction (redox) catalyst found in both animals and plants. As one of the enzymes needed to make ascorbic acid has been lost by mutation during primate evolution, humans must obtain it from the diet; it is, therefore, a vitamin. Most other animals are able to produce this compound in their bodies and do not require it in their diets.
- Ascorbic acid is required for the conversion of the procollagen to collagen by oxidizing proline residues to hydroxyproline. In other cells, it is maintained in its reduced form by reaction with glutathione, which can be catalysed by protein disulfide isomerase and glutaredoxins. Ascorbic acid is a redox catalyst which can reduce, and thereby neutralize, reactive oxygen species such as hydrogen peroxide. In addition to its direct antioxidant effects, ascorbic acid is also a substrate for the redox enzyme ascorbate peroxidase, a function that is particularly important in stress resistance in plants. Ascorbic acid is present at high levels in all parts of plants and can reach concentrations of 20 millimolar in chloroplasts.
- Vitamin E is the collective name for a set of eight related tocopherols and tocotrienols, which are fat-soluble vitamins with antioxidant properties. Of these, α-tocopherol has been most studied as it has the highest bioavailability, with the body preferentially absorbing and metabolizing this form.
- It has been claimed that the α-tocopherol form is the most important lipid-soluble antioxidant and that it protects membranes from oxidation by reacting with lipid radicals produced in the lipid peroxidation chain reaction. This removes the free radical intermediates and prevents the propagation reaction from continuing. This reaction produces oxidised α-tocopheroxyl radicals that can be recycled back to the active reduced form through reduction by other antioxidants, such as ascorbate, retinol or ubiquinol.
- This is in line with findings showing that α-tocopherol, but not water-soluble antioxidants, efficiently protects glutathione peroxidase 4 (GPX4)-deficient cells from cell death. GPx4 is the only known enzyme that efficiently reduces lipid-hydroperoxides within biological membranes.
- Beta-carotene is a fat soluble member of the carotenoids which are considered provitamins because they can be converted to active vitamin A. Beta-carotene is converted to retinol, which is essential for vision. It is a strong antioxidant and is the best quencher of singlet oxygen. However, beta-carotene supplement in doses of 20mg daily for 5-8 years has been associated with an increased risk of lung and prostate cancer and increased total mortality in cigarette smokers (rx). Beta-carotene 20-30mg daily in smokers may also increase cardiovascular mortality by 12% to 26% (rx). These adverse effects do not appear to occur in people who eat foods high in beta-carotene content. Beta-carotene is present in many fruits, grains, oil and vegetables (carrots, green plants, squash, spinach) (rx).
- Lycopene, a carotenoid, possesses antioxidant and antiproliferative properties in animal and in vitro studies on breast, prostate and lung cell lines, although anticancer activity in humans remains controversial (rx, rx,). Lycopene has been found to be very protective, particularly for prostate cancer (rx). Several prospective cohort studies have found associations between high intake of lycopene and reduced incidence of prostate cancer, though not all studies have produced consistent results (rx). The major dietary source of lycopene is tomatoes, with the lycopene in cooked tomatoes, tomato juice and tomato sauce included, being more bioavailable than that in raw tomatoes (rx).
- Se is a trace mineral found in soil, water, vegetables (garlic, onion, grains, nuts, soybean), seafood, meat, liver, yeast (rx). It forms the active site of several antioxidant enzymes including glutathione peroxidase. At low dose, health benefits of Se are antioxidant, anti-carcinogenic and immunomodulator (rx). Selenium is also necessary for the thyroid function (rx). Exceeding the Tolerable Upper Intake Level of 400 μg Se/day can lead to selenosis which is a selenium poisoning characterized by gastrointestinal disorders, hair and nail loss, cirrhosis, pulmonary edema and death (rx).
- Selenium deficiency can occur in patients on total parenteral nutrition (TPN) and in patients with gastrointestinal disorders. In certain China areas with Se poor soil, people have developed a fatal cardiomyopathy called Keshan disease which was cured with Se supplement (rx). The role of Se in cancer prevention has been the subject of recent study and debate. Results from clinical and cohort studies about cancer prevention, especially lung, colorectal, and prostate cancers are mixed (rx, rx).
- Flavonoids are polyphenolic compounds which are present in most plants. According to chemical structure, over 4000 flavonoids have been identified and classified into flavanols, flavanones, flavones, isoflavones, catechins, anthocyanins, proanthocyanidins. Beneficial effects of flavonoids on human health mainly reside in their potent antioxidant activity (rx).
- They have been reported to prevent or delay a number of chronic and degenerative ailments such as cancer, cardiovascular diseases, arthritis, aging, cataract, memory loss, stroke, Alzheimer’s disease, inflammation, infection. Every plant contains a unique combination of flavonoids, which is why different herbs, all rich in these substances, have very different effects on the body (rx). The main natural sources of flavonoids include green tea, grapes (red wine), apple, cocoa (chocolate), ginkgo biloba, soybean, Curcuma, berries, onion, broccoli, etc.
- For example, green tea is a rich source of flavonoids, especially flavonols (catechins) and quercetin. Catechin levels are 4-6 times greater in green tea than in black tea. Many health benefits of green tea reside in its antioxidant, anticarcinogenic, antihypercholesterolemic, antibacterial (dental caries), anti-inflammatory activities (rx).
Omega-3 and omega-6 fatty acids.
- They are essential long-chain polyunsaturated fatty acids because the human body cannot synthesize them. Therefore, they are only derived from food. Omega-3 fatty acids can be found in fat fish (salmon, tuna, halibut, sardines, pollock), krill, algae, walnut, nut oils and flaxseed. However, certain big fishes like tilefish, shark, swordfish are to be avoided because of their high mercury levels (rx).
- There are three major dietary types of omega-3 fatty acids: eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and alpha-linolenic acid (ALA). EPA and DHA are abundant in fish and are directly used by the body; while ALA is found in nuts and has to be converted to DHA and EPA by the body. Dietary sources of omega-6 fatty acids (linoleic acid) include vegetable oils, nuts, cereals, eggs, poultry. It is important to maintain an appropriate balance of omega-3s and omega-6s in the diet, as these two substances work together to promote health (rx, rx).
Benefits of Antioxidants
- Antioxidants come up frequently in discussions about good health and preventing diseases. These powerful substances, which mostly come from the fresh fruits and vegetables we eat, prohibit (and in some cases even prevent), the oxidation of other molecules in the body. The benefits of antioxidants are very important to good health, because if free radicals are left unchallenged, they can cause a wide range of illnesses and chronic diseases.
Antioxidants and Free Radicals
- The human body naturally produces free radicals and the antioxidants to counteract their damaging effects. However, in most cases, free radicals far outnumber the naturally occurring antioxidants. In order to maintain the balance, a continual supply of external sources of antioxidants is necessary in order to obtain the maximum benefits of antioxidants. Antioxidants benefit the body by neutralizing and removing the free radicalsfrom the bloodstream.
Different Antioxidants Benefit Different Parts of the Body
- There are a wide range of antioxidants found in nature, and because they are so varied, different antioxidants provide benefits to different parts of the body. For example, beta-carotene (and other carotenoids) is very beneficial to eye health; lycopene is beneficial for helping maintain prostate health; flavonoids are especially beneficial for heart health; and proanthocyanidins are beneficial for urinary tract health.
Antioxidants and Skin Health Benefits
- When skin is exposed to high levels of ultraviolet light, photo-oxidative damage is induced by the formation of different types of reactive species of oxygen, including singlet oxygen, superoxide radicals, and peroxide radicals. These forms of reactive oxygen damage cellular lipids, proteins, and DNA, and they are considered to be the primary contributors to erythema (sunburn), premature aging of the skin, photodermatoses, and skin cancers.
- Astaxanthin, followed by beta-carotene combined with vitamin E has been shown to be one of the most powerful antioxidant combinations for helping protect the skin from reactive species of oxygen.
Antioxidants and Immune System Support
- Singlet oxygen can compromise the immune system because it has the ability to catalyze the production of free radicals. Astaxanthin and Spirulina have been shown to enhance both the non-specific and specific immune system and to protect cell membranes and cellular DNA from mutation.
- Astaxanthin is the single most powerful quencher of singlet oxygen and is up to ten times stronger than other carotenoids (including beta-carotene), and up to 500 times stronger than alpha tocopherol (Vitamin E), while Spirulina has a variety of antioxidants and other substances that are beneficial in boosting immunity.
Additional Ways Antioxidants Help Benefit One’s Health
Increasing one’s antioxidant intake is essential for optimum health, especially in today’s polluted world. Because the body just can’t keep up with antioxidant production, a good amount of these vitamins, minerals, phytochemicals, and enzymes must come from one’s daily diet. Boosting your antioxidant intake can help provide added protection for the body against:
- Heart problems
- Eye problems
- Memory problems
- Mood disorders
- Immune system problems
Antioxidant Supplementation and Diabetic Kidney Disease
Diabetes’ propensity to cause metabolic derangement is directly responsible for a looming epidemic of diabetic kidney disease (DKD). And left unchecked, DKD can progress to end-stage kidney disease (ESKD).
About 50% of all those with ESKD developed it after a diabetes diagnoses. ESKD’s progression is associated with an increased risk of cardiovascular events and hospitalizations, and those complications escalate in patients who need chronic renal replacement therapy by dialysis or kidney transplant.
A team of researchers from Italy has published a review and meta-analysis in the journal PLOS ONEthat examines use of chronic antioxidant supplementation as a tool to retard kidney disease progression in patients who have diabetes.
The authors looked at many studies that used various antioxidants in an attempt to slow DKD. They found multiple randomized controlled trials but had difficulty comparing and contrasting the results due to varying sample sizes, study designs, and outcome measures.
One area in which there was considerable diversity was the definition of kidney disease progression to end stage. Some studies defined this point as a need for chronic dialysis or kidney transplant, but other studies used surrogate endpoints such as changes in urinary albumin excretion or renal function.
Overall, the researchers concluded that studies have shown that the use of antioxidants can reduce albuminuria. This finding is encouraging because pathological urinary albumin excretion is an early sign of DKD. In this meta-analysis, the researchers found that antioxidant supplementation was associated with significant reductions in albumin excretion.
Studies employed many antioxidants including vitamin C, vitamin E, zinc, and silymarin. Several studies used oxidants in combination. Evidence was strongest for vitamin E in doses ranging from 480 mg to 1200 mg daily.
Most studies indicated that participants reported no significant adverse events, though a few studies did not seem to examine adverse events systematically.
The authors reported that additional studies are needed to determine which oxidants and at what dose) are most likely to slow DKD progression. They also indicated the need for better definitions of outcomes.
Workhorse Vitamin: A Primer on Vitamin B12
The July 2017 issue of Nature Reviews Disease Primers includes a disease primer that discusses the epidemiology, mechanism/pathophysiology, diagnosis/screening, prevention, and management of vitamin B12 deficiency.
B12 status varies through the lifetime, creating a need to consider patient factors when interpreting diagnostic biomarkers of B12 status. Inadequate intake, impaired absorption, chemical inactivation, or inherited B12 transport or metabolism impairment may lead to deficiency. Diagnosis is critical because B12 deficiency can be life-threatening.
Clinical B12 deficiency with hematological and neurological manifestations is relatively uncommon. On the other hand, 2.5-26% of the general population has subclinical deficiency and it’s unclear if these people will progress to deficiency or continue to have low but stable B12 levels.
B12 deficiency’s signs and symptoms are weakness, constipation, numbness and tingling in the hands and feet, confusion, poor memory, and mouth or tongue soreness. Vitamin B12 deficiency can affect individuals at any age, but vegans and elders are at increased risk. It is often difficult to diagnose elderly patients because its typical clinical manifestations are absent or are confused with dementia.
Increased consumption of animal products and fortified foods may prevent B12 deficiency, as will oral or parenteral B12 supplementation. Initially, higher doses are required to replete B12 stores in the body.
Hematologic abnormalities respond to B12 treatment in about 5 days and completely recover in 4 to 6 weeks. Neurological abnormalities are slower to correct. B12 deficiency not due to nutritional deficiency may require lifelong treatment.
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