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ALL ABOUT OXIDATIVE STRESS
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Did you know
- Any word that starts with Oxy or Oxi is all about oxygen
- We can’t live without the element Oxygen, but at the same time it is slowly aging and eventually killing us
- Oxygen is the foundation of a process in the body called Oxi-dation
- Oxi-dation is a normal and necessary process that takes place all over the body
- Oxi-dation can be beneficial or harmful.
- Oxi-dative damage is the main driving force in the aging process
- When a molecule is Oxi-dized the oxygen part of it loses a little part of its atom called an electron
- This creates a whole new molecule known as a free radical or Reactive Oxygen Species – ROS for short
- Free radicals are reactive, unstable oxygen containing molecules, desperate to replace the electron, which they ’steal’ from other molecules
- The ‘stealing’ makes the other molecules unstable
- The new molecules start ‘stealing creating a chain reaction
- When molecules lose electrons their function is impaired
- The only known way to stabilise free radicals is with antioxi-dants
- Antioxi-dants donate an electron to a free radical without making themselves unstable, thus stopping the chain reaction
- Oxi-dative stress occurs when there’s an imbalance between free radical activity and antioxidant activity.
- Free radicals are not always bad per say
- They are amongst other things an essential part of our immune defence
- BUT when there are more free radicals than antioxidants to keep them in check, oxi-dative stress occurs with tissue damage and disease to follow
- Free radicals damaging fatty tissue, such as cell membranes DNA, and proteins, such as enzymes
- Pretty much all body molecules and tissues can be damaged by free radicals
- Polyunsaturated fatty acids, particularly Omega 6 arachidonic acid and linoleic acid, are primary targets for free radicals
- Free radical damage can speed up aging and lead to a vast number of disease states over time
- Approx. 2- 5 % of every breath of oxygen we breathe will become a free radical.
Meet Sally and get to know all about oxidative stress
Intro
Oxidative stress 101
Free radicals 101
Oxidative stress & cancer
Oxidative stress 101
- Is the term used to indicate the imbalance between the amount of Free radicals and the body’s ability to neutralize them, ie antioxidants and the resulting tissue damage.
- Can be measured by the ratio of stable glutathione to oxidized unstable glutathione within cells
- Oxidative stress cause chronic inflammation and is suspected to be involved in the development of most disease states, such cancer
– Cancer
– Parkinson’s
– Alzheimer’s
– Atherosclerosis
– Cardiac arrest
– Diabetes
– Blood clots
– Autism
– Chronic fatigue syndrome
– Etc.
BUT
- Is very beneficial when used by the immune system to:
– Attack and kill invaders, such as bacteria, viruses, etc
– Destroy old, unhealthy cells
– Etc.
Free Radicals 101
- Are unstable oxygen containing molecules.
- Are molecules with one or more unpaired electron desperately ‘searching’ for an electron to ‘steal’ from other molecules, such as DNA, cell membranes, etc
- Are common by-products of metabolism/energy production (ATP)
- Act as signalling molecules in the immune system.
- Under certain conditions an oxidative burst can occur, where free radical levels can rise sharply and if left unchecked cellular damage can occur
- Molecules called antioxidants freely give up an electron to stabilise the free radicals
Examples of Free Radicals
- Superoxide – most common free radical in the body
- Hydrogen peroxide aka bleach
- Hydroxyl radical
- Nitric oxide radical.
Conditions that Increase Free Radical Production
- Normal essential metabolic processes, such as energy / ATP production
- Will increase during exercise
- Exposure to ‘invaders’, bacteria, viruses, etc
- Exposure to environmental irritants, such as
– X-rays
– UV-rays
– Cigarette smoke
– Air pollutants
– Ozone / O3 which is a type of oxygen
– Industrial chemicals, such as pesticides.
Adverse effects of Free Radicals are
- DNA damage – cancers
- Oxidation of polyunsaturated fatty acids, especially omega 6 fatty acids – cell membrane damage
- Oxidation of amino acids – enzyme function
- Oxidation in the mitochondria – disturbed energy production.
Free Radical Protection
- The only known solution to free radicals are antioxidants
- Antioxidants add an electron and thereby reduce or make the molecule stable and stop the chain reaction.
Antioxidants 101
- Are substances that freely give up an electron
- The electron is used by the body to stop / prevent / control / balance oxidation.
- Also used in cosmetics and foods, as preservatives to prolong shelf life.
Two Types
Primary Antioxidants
- Produced by the body, such as
- Glutathione
- Various enzymes such as:
– Glutathione peroxidase
– Catalase
– Superoxide dismutase
Secondary Antioxidants
- Obtained through the diet, such as
– Vitamin C
– Vitamin E
– CoQ10
– Melatonin.
Primary antioxidants
- Also called internal or endogenous
- Inhibit the formation of new radicals
- Production is controlled by various gene SNP’s and enzyme co-factors essential for their production
- These primary antioxidants can act again and again
- Deactivate between 10,000 and 100,000 free radicals per second
Primary antioxidants include
- Glutathione
- Antioxidant Enzymes
– Superoxide Dismutase/SOD
– Reacts with the free radical superoxide to create oxygen and hydrogen peroxide.
– There are 3 types of superoxide dismutase:
- SOD1 found most in cytoplasm (cell fluid)
- SOD2 in mitochondria
- SOD3 is extracellular (plasma).
– Catalase/CAT
– Reacts with the free radical hydrogen peroxide to create water and oxygen.
– Glutathione Peroxidase
– Reduces the free radical hydrogen peroxide to water.
Essential Nutrients for Antioxidant Enzyme Production
Micro-nutrients
- SOD1 needs Copper and Zinc
- SOD2 needs Manganese
- SOD3 needs Copper and Zinc
- Glutathione Peroxidase needs Selenium
- CAT needs Iron
Good Food sources
- Selenium – Brazil nuts
- Iron – Organ/red meats, dark green veggie (cooked)
- Copper – beef liver, sunflower seeds
- Zinc – oysters and other shell fish, organ meats, pumpkin seeds
- Manganese – shell fish, fruit, leafy greens
Good supplements
Glutathione
- The body’s major antioxidant
- Prevents damage to important cellular components caused by free radicals, through its involvement on the enzyme glutathione peroxidase
- Glutathione exists in 2 states
- reduced / stable – GSH
- oxidized / unstable – GSSG
- The ratio of GSH to GSSG within cells is a measure of cellular oxidative stress, where increased GSSG -to-GSH ratio is an indicator of greater oxidative stress.
- In healthy cells and tissue, more than 90% of glutathione is in its stable form as GSH
- Recycled continually through the Redox cycle
- Also necessary for
– the production of immune molecules leukotrienes and prostaglandins
– the storage of the amino acid cysteine
– enhances the function of the nitric oxide cycle
– as a cofactor in enzyme activity
– important for conjugation in phase 2 liver detoxification pathways
– may also be a neuromodulator
Increasing Glutathione
- Foods
– asparagus
– avocados
– okra
– spinach
Supplements
- Glutathione best absorbed in lipo form – BUY HERE
- or as NAC/N-acetylcysteine – BUY HERE
- or as ALA/Alpha Lipoic Acid – BUY HERE
- Hormetic Supplements
– Sulforaphane is a natural plant substance found in many cruciferous vegetables, such as broccoli (especially sprouts), cabbage, cauliflower, and kale. These vegetables contain the inactive substance glucoraphanin, which is a glucosinolate (careful glucosinolate can prevent the uptake of iodine) Glucoraphanin is converted to sulforaphane by the enzyme myrosinase, which is produced when the vegetable is cut or chewed.
For the largest production of sulforaphane, the vegetables should preferably be raw, however, a dietary supplement of sulforaphane will contain the largest amount.
The challenge of eating the raw vegetables is that they also contain anti-nutrients, such as oxalic acid, which can prevent the absorption of the mineral’s calcium and iron, as well as create kidney stones.
Sulforaphane works by activating NrF2 – (Nuclear Factor Erythroid 2-related Factor), which is a transcription factor for the genes involved in oxidative stress, inflammation, immune response, energy production, liver detoxification and methylation, and thus considered ‘the master switch’ and a multi-body protector.
When choosing sulforaphane supplements, it is important that they contain both glucoraphanin and myrosinase and NOT sulforaphane. Sulforaphane is produced when the supplement comes in contact with water and myrosinase is activated, then sulforaphane is kept active for approx. 25 minutes.
10 -20 gm sulforaphane per day is optimal
This product Broccolox produces 10gm per capsule/per serving – BUY HERE
Hometic Lifestyle
– extreme temperature changes, ie. hot and cold showers,
– H:I:T exercise and training
– Intermittent fasting or TRE-Time Restricted Eating
– increase the hormesis effect turning on the body’s natural ‘survival’ responses, such as activating NrF2 – (Nuclear Factor Erythroid 2-related Factor), which increase production of glutathione.
Secondary antioxidants
- Also called external
- Neutralise / stabilize free radicals.
- Often by forming an “antioxidant radical” that has a reactivity significantly less than the ‘free radical’.
- These antioxidants only work once and therefore need to be added continuously.
- Secondary antioxidants include
Uric acid – important extracellular/plasma antioxidant
Bilirubin
Albumin
Vitamins A, C, E and D
CoQ10
Melatonin
- Foods containing antioxidants
Organ meats
Honey
Fruits, such as apples, blackberries, blueberries, cantaloupe, pomegranates, cherries, cranberries, grapes, pears, plums, raspberries, Aronia berries, and strawberries
Vegetables, such as broccoli, white cabbage, celery, onions and parsley
Red wine
Dark Chocolate
Black, green, and white teas
Olive oil
- Important to replenish antioxidants from foods on a daily basis every meal for optimal levels.
- Content of antioxidants in foods is measured using ORAC (Oxygen Radical Absorbance Capacity)
- ORAC is a lab test that attempts to quantify the “total antioxidant capacity” (TAC) of a food by placing a sample of the food in a test tube, along with certain molecules that generate free radical activity and other molecules that are vulnerable to oxidation. The sample is then measured for free radicals, the less there are, the higher the antioxidant capacity of the test food.
- ORAC values for fruit and vegetables are expressed as ORAC units per 100 g.
- The recommended daily dose is a minimum of 5000 ORAC, but 10,000 may be most optimal.
Supplements
Measuring Oxidative Stress
The following tests can be used to obtain a picture of the level, the possible cause and how oxidative stress is affecting the body
Blood test
- ADMA – Asymmetric dimethylarginine
DNA SNPs
- SOD1, SOD2, SOD3, GPx, CAT, eNOS,
- DNA health – measures them all – BUY HERE
Co-factors
- Copper/Cu, Zinc/Zn, Manganese/Mn, Iron/Fe, Selenium/Se,
- Metabolomix – will test some of them – BUY HERE
Oxidative stress levels
- Urine levels of 8-Hydroxyguanosine (8-OHG) – indicates DNA damage
- Urine levels of p-Hydroxyphenyllactate – indicates higher cell turnover
- Urine levels of Lipid peroxidase – indicates oxidised fatty acids
Various test
- Organix Comprehensive – measures p-Hydroxyphenyllactate and 8-OHG – BUY HERE
- DUTCH complete measures 8-OHG – BUY HERE
- Metabolomix measures 8-OHG and lipid peroxidase – BUY HERE
- Oxidative Damage measure 8-OHdG – BUY HERE
Antioxidant Tests
Measures both primary and secondary antioxidants through urine
ORAC Values per 100g of some Common Foods
Cloves, ground
314446
Cinnamon, ground
267536
Oregano, dried
200129
Turmeric, ground
159277
Acai berry, freeze-dried
102700
Cocoa, dry powder, unsweetened
80933
Peppermint, fresh
13978
Oregano, fresh
13970
Walnuts
13541
Hazelnuts
9645
Cranberries, raw
9584
Kidney Beans, raw
8459
Black Beans, raw
8040
Pistachio nuts, raw
7983
Pinto Beans, raw
7779
Lentils, raw
7282
Raspberries, raw
4882
Basil, fresh
4805
Almonds
4454
Red Delicious apples, raw with skin
4275
Peaches
4222
Raisins
4188
Granny Smith apples, raw, with skin
3898
Figs, raw
3383
Cherries, sweet, raw
3365
Gooseberries, raw
3277
Apricots
3234
Peanuts raw
3166
Cabbage, cooked
3145
Broccoli, raw
3083
NB!
Many of these values are based on raw foods, such as various beans and lentil, which is not how they are consumed.
Cooking will decrease the ORAC values as vitamins are destroyed by heat.
Oxidative stress & Cancer
- Cancer initiation and progression have been associated with oxidative stress by:
– enhancing DNA mutations
– increasing DNA damage
– genome variability
– cell proliferation
– uncontrolled growth of cells which encourages the development of tumours
– increase in oncogene activity
- Due to higher energy production to aid tumour growth, cancer cells increase their rate of ROS production compared with normal cells.
- At the same time in order to maintain ROS balance and evade cell death, cancer cells also increase their antioxidant capacity.
- Bimolecular reactions cause free radicals to create compounds as malondialdehyde (MDA) and hydroxyguanosine.
- These substances can be measured in urine and can be used as indicators of oxidative stress and to evaluate cancer risk – see article on testing oxidative stress for more information.
Testing Oxidative Stress Levels
- Urine levels of 8-Hydroxyguanosine (8-OHG) = DNA damage
- Urine levels of p-Hydroxyphenyllactate = higher cell turnover
- Urine levels of Lipid peroxidase / malondialdehyde = oxidised fatty acids
Organix Comprehensive
- measures p-Hydroxyphenyllactate and 8-OHG – BUY HERE
DUTCH complete
- Measures 8-OHG – BUY HERE
Metabolomix
- Measures 8-OHG and lipid peroxidase – BUY HERE
Oxidative Damage
- Measure 8-OHdG – BUY HERE
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