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First on my bucket list is the quenching or rendering harmless of free radicals and related reactive oxygens
Many decades ago, my free-radical research brought me to the conclusion that free radicals and reactive oxygens are extremely deleterious to our bodies.
During only an eleven-month exercise period, the physiques of these six individuals above improved enormously. Observe carefully their improved physiques. However, notice how their heads, faces and hair color have deteriorated SIGNIFICANTLY during only eleven months. Indeed, their heads have aged at least 5 years in the space of less than one year! For example, observe the greying of their hair and the wrinkling and aging of their facial skin.
Allow me to explain why this acceleration in aging has occurred.
Biologists tell us that at some point in the evolution of our planet, blue-green algae came into being and free oxygen became available. This development allowed an increased energy yield from food by aerobic metabolism.
A comparison of anaerobic and aerobic organisms reveals that the latter have found it essential to develop multiple lines of defense to prevent or minimize unwanted and damaging oxidation reactions.
On the other hand, anaerobic organisms find oxygen lethal because they lack all defenses. To the physicist, molecular oxygen can be lethal for reasons of its triplet ground state, electron spins, and its conservation of angular momentum. To the non-physicist, this means that molecular oxygen can easily share its electrons, and we often call this process oxidation.
On the other hand, aerobic organisms including humans must have multiple lines of defense against lethal oxygen. Oxygen is lethal and toxic and requires multiple lines of defense to protect against oxidative damages, especially inside our cells and within our mitochondrial respiratory chain. Note that this form of mammalian oxidation involves the controlled burning of oxygen combined with fats and sugars.
CONTROLLED MITOCHONDRIAL BURNING
First, this controlled process is 92 to 96 percent efficient in human mitochondria as determined by my research 35 years ago. This high rate of efficiency compares favorably with the 97 percent efficiency of large electric motors.
This high cellular efficiency can be further improved by daily consumption of nutrients such as CoQ10, or ubiquinol, which helps facilitate better electron transport in the respiratory chain of mitochondria.
Other controlling factors of mitochondrial respiration are the thyroid hormones, T3 and T4, and the pituitary hormone, HGH, or growth hormone.
During aging, this high efficiency can also be improved in our skin and internal organs that accumulate lipofuscin or age pigment containing oxidized lipids.
Why Are Free Radicals Toxic?
Unfortunately, the remaining 4 to 8 percent of our mitochondrial oxidation discussed previously converts to toxic free radicals and reactive oxygens, such as hydrogen peroxide, superoxide, lipid peroxides, singlet oxygen, and, most dangerous of all, the hydroxyl radical (symbol •OH ).
This dangerous radical is also generated outside our bodies when radiation hits our cells and damages our DNA and its telomeres. And, guess what, our bodies experience approximately 7,000 radical ‘hits’ daily to our DNA.
A poignant example of the incredible destructive power of hydroxyl radicals may be seen in the nuclear explosions of Hiroshima and Nagasaki that occurred at the end of WW2. In the survivors, hydroxyl radicals damaged their DNA and oxidized their bodies in nanoseconds!
Those survivors with good hormone and stem-cell repair systems were able to rebuild and regenerate their bodies and their DNA. Efficient glial cells in the brain removed toxic waste products.
Furthermore, today, some 70 years later, survivors that I know personally as patients are healthy and living vibrant lives during their advanced senior years due to their bodies natural healing stem cells supported by ‘growth promoters’ such as IGF-1, HGH and a 7 other related growth promoters.
Why Hydroxyl Radicals Are One of the Most Toxic Substances on the Planet?
Hydroxyl radicals are definitely one of the most dangerous substances for humans on the planet with toxicity thousands of times greater than arsenic, cyanide, botulism, and many other indigenous enzyme oxidants.
And guess what: we have no natural enzymatic defenses against hydroxyl radicals because their lifespan is measured in nanoseconds. This extremely short lifespan means that damage to living cells is done almost instantaneously, and no known defense exists to interfere with this near-instant destructive force.
As a consequence, damage must be repaired, for example, with DNA repair enzymes, or we may develop cancer. This repair occurs with the help of hormones or nutrients such as the pseudo-hormone vitamin D3.
Or given a second example, a hydroxyl radical attack on unsaturated fatty acids. This attack generates huge amounts of lipid peroxides in chain reactions. I measured this chain reaction in vivo and non-invasively in human volunteers and found that people who used interveneous drugs such as methamphetamine exhibit the fastest increase of lipid peroxides.
These chain reactions give rise to tissue damages that can only be prevented by a termination of the chain reaction using an antioxidant or free radical scavenger. If this chain reaction is not terminated, massive accumulation of age pigment called lipofuscin occurs. Examples of lipofuscin massive accumulation are found in Batten’s disease.
For example, purified neural stem cells were injected into the brain of Daniel Kerner, a six-year-old child with Batten disease, who had lost the ability to walk and talk. This patient was the first of six to receive the injection of a stem cell product from StemCells Inc., a Palo Alto biotech company. These are believed to be the first-ever transplants of fetal stem cells into the human brain.[15] Within a few months, the child had recovered well enough to return home, and some signs of speech returning were reported.
A third method uses stem cells to replace our old, damaged, and oxidized cells with new cells. These stem cells originate in bone marrow or fat cells, and approximately seven vital growth promoters encourage their use. One example of a growth promoter is the hormone IGF-1 or insulin-like growth factor one.
These seven are, in turn, dependent upon a sufficient supply of anabolic hormones, especially hGH or human growth hormone and IGF- 1. Unfortunately, because of declining endocrine output, these anabolic hormones become increasingly deficient during aging, especially for those over fifty years of age.
What are Our Four Lines of Defense Against Active Oxygens and Radicals?
During the 1980s, my research firmly established that human mitochondria are only 92 to 96 percent efficient, and, we all have four lines of defense to render active oxygens and free radicals harmless (1).
First Line of Defense
I call our first line of defense SOD, or superoxide dismutase. In a long series of reactions, SOD renders harmless the superoxide anion radical (symbol O 2• ) to ordinary water and oxygen.
We can double the activity of SOD with a least an hour of daily exercise. Also, SOD is dependent upon daily trace amounts in our diet of the transition metals manganese, zinc, and copper. These are essential to SOD’s formation, function and active site. Molecular chemists tell us that transition metals have long d-orbitals extending far out into molecular space. These d-orbitals easily release and accept electrons that are passed on to other d-orbitals in a bucket brigade fashion. (Indeed, this is how electricity moves along a copper wire.) 34
Interestingly, people engaged in very heavy aerobic exercise generate large quantities of free radicals and ROS that can only be deactivated by SOD and its transition-metal/d-orbital active sites. Unfortunately however, very heavy aerobic exercise generates free radicals and ROS EIGHT TIMES in excess of what the SOD first line of defense can deactivate. An 8-times excess causes damages to living tissue and DNA unless other lines of defense can help.
Superoxide was injected into the bloodstream of hamsters, and ischemic arterial damage resulted. This induced ischemia was totally reversed when strong antioxidants such as glutathione were subsequently injected into damaged arteries.
Experiments in animals have revealed that the powerful superoxide anion radical causes arterial ischemic damage. Note that these arterial damages are what we have observed in people engaged in very heavy aerobic exercise as revealed in a previous slide.
Our second line of defense is what I call membrane-bound vitamins E or tocopherols. These antioxidants further eliminate some active oxygens that have escaped the first line of defense. However, this second line of defense is highly limited because the membranes of our cells and mitochondria cannot contain more than 2 percent vitamin E molecules by volume.
On the bright side, recent research (3) has indicated that a potent vitamin-E –type antioxidant, called tocotrienol, concentrates in the membranes of endothelial cells. In rodent experiments, 40 percent of mice receiving tocotrienol survived a lethal dose of hydroxyl-radical- type radiation versus 100 percent of control mice that died.
Second, in human clinical studies, tocotrienols are known to significantly reduce incidence of stroke and loss of connectivity between different areas of the brain.
Third, tocotrienols work against inflammation especially when combined with other antioxidants. One significant anti-inflammatory effect is a reduction of arterial ‘stiffness’.
In summary, special types of vitamin E seem to reduce some of the toxic effects of free radicals and protect vital membranes and DNA. However, ordinary vitamin E such as drugstore dl-alpha tocopherol does not correlate with increased longevity in research animals.
Third Line of Defense
Our third lines of defense against the toxic byproducts of the mitochondrial respiratory chain are the enzymes glutathione peroxidase and catalase. With the help of transition metals, selenium and iron, they reduce hydrogen peroxide, symbol H2O2, to ordinary water. [Note parenthetically that “transition metals” often include selenium, iron, zinc, copper, and manganese. At the molecular level, these metals have the unique ability to receive or give off an electron as seen in electrical transmission in copper wires. Molecularly speaking, they have long and loose “d” orbitals. ]
Contrary to what many people believe, hydrogen peroxide is a weak oxidant, I repeat, a weak oxidant and not a free radical! I cannot emphasize this point enough because many people continue to believe otherwise. Hairdressers routinely use hydrogen peroxide to bleach hair. If we put a few drops of drugstore hydrogen peroxide on a finger, it will temporarily discolor the skin, rendering it a sickly white color.
It is important to note that our catalase-and-glutathione- peroxidase line of defense declines as we age, and thus our ability to convert hydrogen peroxide to water is progressively impaired.
As a result, recent studies (2) have demonstrated that increasing amounts of hydrogen peroxide causes the greying and whitening of our hair and the loss of pigment in our skin. However, no correlation exists between longevity and hydrogen peroxide since, again, H2O2 is a weak oxidant.
In contrast, an example of a strong oxidant is the active ingredient in common bleach. Bleach contains chlorine dioxide gas that is generated when sodium hypochlorite is added to our swimming pools or drinking water.
NaOCl + 1⁄2O2 -------------------- ClO2 (g)
Fourth Line of Defense: The connection between the free-radical scavenger, glutathione, and hormone, IGF-1.
Our fourth line of defense is the ubiquitous and powerful antioxidant glutathione. According to recent research (1,3), our bodies only produce sufficient antioxidants such as glutathione by maintaining youthful levels of powerful anabolic hormones such as IGF-1 or insulin-like growth factor one and hGH or human growth hormone. In fact, a positive linear relationship exists in vivo between IGF-1 and glutathione concentrations (4,5).
For example, according to Higashi et al. (2013), quote “The observed antioxidant effect of IGF-1 may contribute to maintaining vascular integrity by counteracting oxidative stress, thereby limiting atherosclerosis development.” unquote (6).
And second, from Brown-Borg et.al. (2005) quote: “The current results support a role for growth hormone in the regulation of antioxidant defense and ultimately, lifespan in organisms with altered GH or IGF-1 signaling.” unquote.
And third, (2007) quote: “. . . . One major mechanism underlying the anti-atherogenic effect of IGF-1 could be an antioxidant effect targeting the endothelium and leading to decreases in aortic superoxide levels.”” unquote (7).
During aging, we develop increasing and ongoing deficiencies of these two vital anabolics (hGH and its downstream product IGF-1) as well as decreasing levels of many other essential anabolics, such as testosterone, estradiol, DHEA, and melanocyte stimulating hormone or MSH2.
In other words, in our youth we are drowning in a tsunami of hormones, but eventually in our senior years we are chasing the fumes of hormone deficiencies.
Thus, these deficiencies cause a further deficiency of our fourth line of defense, namely glutathione. Unfortunately, we cannot supplement glutathione or these hormones with oral tablets or capsules for two reasons: 1) Poor gut absorptivity.
2) With the single exception of DHEA, hormones should not be taken orally because they will first pass through the liver and altered chemically by liver enzymes. Thus, hormones are best supplemented by other means such as by injection, intra- nasally, topically, or sublingually. (See NaturalsPro.com)
Interestingly, in the case of glutathione, our vital lung epithelial cells must maintain high concentrations of it during aging, or we may develop asthma, chronic obstructive pulmonary disorder or COPD, or other lung problems.
By ‘high concentrations,’ I mean that our epithelial lung cells should maintain a normal gradient of 140:1, that is to say, lung-cell glutathione versus bloodstream glutathione. Mother Nature has determined this 140:1 gradient, and we should follow her advice.
This extreme gradient renders harmless the active oxygens and free radicals formed in our sensitive lung cells when we breathe pounds of oxygen daily (1).
Thus, One May Ask: Is it Dangerous to Breathe?
Our sensitive lung cells continuously absorb oxygen gas. In order to prevent oxidative tissue damage—think rusting iron or rancid nuts and oils such as rancid flaxseed oil—we must prevent oxidative damage by generating large quantities of fresh glutathione daily.
On the other hand, when asthma patients inhale synthetic, patented medicines such as corticosteroid sprays, these remedies increase epithelial cell metabolism and perhaps even increase glutathione somewhat. But after many years of ‘revving up the system’ with synthetic steroids, serious side effects often develop such as osteopenia.
These lung difficulties and side effects can be overcome by employing completely natural solutions. Instead of using synthetic inhalers, asthma and other lung disorders can often be successfully remedied by inhaling l-glutathione powder.
Glutathione inhalation supports the 140:1 glutathione gradient. Also, it improves tissue bioavailability in our free-radical sensitive epithelial lung cells. The effect does not occur by ingesting oral tablets or capsules of glutathione.
Better gradient support and bioavailability relieves symptoms of asthma, COPD, and other lung difficulties within a few minutes of application.
[Parenthetically, better bioavailability can also be achieved in the case of natural aldosterone, namely AldoMax. Properly dissolved aldosterone sprayed directly in the ear canals improves age-related hearing loss by 30 to 40 decibels as well as improved word recognition. There is a patent pending on this subject.]
What Happens with Deficiencies In Our Four Lines of Defense?
If there are deficiencies in the four lines of defense, our bodies naturally respond with inflammation. Inflammation is the underpinning of all age-related diseases, including cardiovascular and cerebrovascular disease, diabetes and cancer. Inflammation is commonly measured with C-reactive protein, and it is visibly apparent as edema.
Edema causes a puffy appearance, which is seen even in otherwise healthy and athletic people such as Arnold Schwarzenegger.
If you doubt these statements, please peruse past and present photos of movie stars. You will observe that even though this actor and others are very muscular and athletic as they were during their younger days, both have acquired edema due to inflammation caused by unchecked free radicals and active oxygens that have run amok and damaged tissue.
In other words, free radicals and active oxygens have avoided or escaped their four lines of defense, causing havoc and edema throughout their bodies and especially in their facial tissues. As stated by Dr. Barry Sears, “Inflammation must be turned off.”
Thus, I strongly recommend the consumption of natural anti-inflammatories such as omega 3s, polyphenols, curcumin, ginger, quercetin, alpha lipoic acid, and especially Boswellia several times daily.
Boswellia, combined with hydrocortisone and DHEA, works wonders by abating swelling and dark circles around the orbitals of the eyes. Note that DHEA is well known both as an anabolic steroid and an anti-inflammatory. Still another natural hormonal anti-inflammatory is progesterone and not its synthetic analogs, the progestins.
Eminent antiaging scientist Dr. Ward Dean has written numerous articles about Boswellia, and he recommends it as his premier anti-inflammatory treatment.
Why are Free Radicals and Heavy
Aerobic Exercise Dangerous to Health and Aging?
Free radicals are dangerous to one’s health, especially in the case of athletes engaging in very heavy aerobic exercise that uses daily kilograms of oxygen, which in turn, generate grams of deadly free radicals.
To further explain, it is well established since the 70’s by Fridovich, McCord, and others that very heavy exercise generates a superoxide-radical cascade eight times greater than our SOD defense can handle (1). Thus, the escaping radicals cause edema, DNA damage, and visible signs of aging especially in species other than humans such as naked mole rats, and some species of bats that have very strong lines of defense.
Furthermore, radical damages are especially apparent in high performance athletes. For example, consider all the athletes who live normal lifespans between 75 and 85 years and participated in relatively low-aerobic sports such as swimming, tennis, or golfing. On the other hand, compare them to those who played very heavy aerobic sports and had shortened lifespans such as double Olympic gold-metal winner Jesse Owens who died at the early age of 68!
Others include Joe Louis, Sugar Ray Robinson, Jackie Robinson, and Babe Didrickson – All of who died prematurely from natural causes in their sixties or even younger.
A good example of this phenomenon is the star baseball player Jackie Robinson who died at age 53 from diabetes and heart disease. Note also that none of these famous athletes had serious sports injuries that would account for their shortened lives.
Parenthetically, shortened lives are common in India where ordinary vegetarian laborers work very hard aerobically and die on average at age 55. On the other hand, overweight Indian moneylenders, who sit all day and count money, die on average at age 75 like many Westerners (9).
Thus, heavy physical labor or heavy sports burns up a body. Make no mistake.
Depicted at the beginning of this essay are before-and-after photos taken only 11 months apart. To enhance their bodies, these people practiced very heavy aerobic exercises without protecting themselves with effective free-radical scavengers – not weak vitamins such as ordinary vitamin C and E.
Observe that the right-hand photos above show significant improvements in body and muscle tone. However, their whitened hair and changed faces reveal rapid aging due to extensive free-radical and cross-linking damages.
Indeed in this slide, extreme exercise without effective free-radical protection has caused nasolabial folds and facial grooves such as periorbital rhytids, as well as whitening of the hair during a period of only 11 months! -------------------
While we are focusing on athletes, allow me to diverge and add some comments on the enhancement of their athletic abilities during aging.
During the years 1990 to 2004, some US athletes freely used steroids such as human growth hormone and IGF-1 to slow their aging and enhance their sports abilities. In particular, US baseball players extended their participation in baseball from their peak years of 26 to 30 to their late thirties or even early forties. They did this through hormone corrective therapy that was not strictly forbidden during the 14-year period from 1990 to 2004 (10).
For example, Barry Bonds hit 258 home runs in his five sessions between ages 35 and 39 years –an average of 51 home runs per year. Roger Clemens led the National League in earned-run average at age 42!
Thanks to the enhancing abilities of hormone corrections and subsequent glutathione boost, these athletes achieved a “second-wind” with feats of athletic prowess never seen before or since! (10).
Interestingly, IGF-1 is a key component in producing vital antioxidants such as glutathione, and it has been well established in more than 240 research publications that it also enhances body firmness, memory, physical stamina, and especially brain speed (11).
Conclusion
Many of the most toxic substances for humans on the planet are generated either internally in our cells or externally by radiation. As we age, we naturally defend against these toxins with our cells’ four lines of defense. When these defenses fail, we develop some problems of aging, such as edema, atherosclerosis, breathing difficulties and slowed brain speed.
First, we need to recognize these difficulties and deficiencies with lab tests and visual observation of our patients. Second, we need to boost our four lines of defense with corrective supplements.
In truth, in humans, more efficient lines of defense encourage fewer radical damages and longer, healthier lifespans. As first established by Harmon, Fridovich, McCord, and other researchers; humans, certain bat species, and the naked mole rat seem to be endowed by Mother Nature with strong free-radical lines of defense. These defenses allow long lives compared to most other animals despite environmental stresses that cause free-radical generation. Second, as established by Dr. Séquard in Paris 140 years ago and Dr. Henrickson today, Mother Nature has endowed us with strong endocrine glands and stem cells that effectively repair damages from aging and free radicals, but unfortunately, these glands decline in hormone output during aging. Thus, for increased longevity and quality of life, we need to correct hormone deficiencies and supplement free-radical scavengers or a daily or perhaps a twice-daily regimen.
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