How Do Free Radicals Damage Us and Hormone Repair Keep Us Youthful?

 In the United States, the average 65-year-old has five major diseases—diagnosed or undiagnosed—that require 9 to 20 medications daily. This occurs during aging with a progressively declining quality of life, and I want to do something about it instead of the tried-and-true methods using massive amounts of meds and palliative care.  Since 1972, I have firmly believed that aging should be reversed. Since then, I have focused on the damages caused by free radicals and repairs by hormones andnutrients.

 I promise you that recent research into the causes of aging and the reversal of aging will help you to significantly improve the quality of life for your patients with less of a need for prescription meds.

 What do I mean exactly?

 Well, researchers have recently discovered numerous remedies that

• Quench or render harmless free radicals and reactive oxygen species or
• Correcting deficient hormones and nutrients that will ad years to your life and life to your

 With these new treatments, those with free radical and active oxygen damages-- shown in slide one-- will be able to minimize future damages causing premature aging. Second, those with damaged  faces,  necks, hair and bodies will now be able to reverse those damages given the latest techniques in corrective hormone and nutrient therapies as seen   in slide two). When these two remedies are fully implemented, I   promise you that your compliant patients will look and become physiologically younger by several decades. In my own case, I am chronologically 73-years-young, but my appearance, blood work, and stress EKG-test results indicate a person in his forties. As a result of reversed aging, energy and vitality are also restored.  This reversal  yields a more ambitious and happy individual who will look forward to years of creativity and newaccomplishments.

 Wouldn’t you want to spend your remaining years of your life embracing again the creativity and excitement of your middle-aged years rather than enduring the infirmities of oldage?

 First on my bucket list is the quenching or rendering harmless of free radicals and related active oxygens

 Many decades ago, my free-radical research brought me to the conclusion that free radicals and active oxygens are extremely deleterious to our bodies. Observe slide one. During only an eleven- month exercise period, the physiques of these six individuals improved enormously. Observe carefully their improved physiques. However, notice how their heads, faces and hair color have deteriorated during only eleven months. Indeed, their heads have aged at least 5 years during  the space of less than a year! For example, notice the greying of their hair and notice the wrinkling and aging of their facialskin.

 Allow me to explain in detail 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 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 processoxidation.

 On the other hand, aerobic organism 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

 ŸThis 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.

Allow me to pose the Question: Why Are Free RadicalsToxic?

Unfortunately, the remaining 4 to 8 percent of our mitochondrial oxidation discussed previously converts to toxic free radicals and active oxygens, such as hydrogen peroxide, superoxide, lipid peroxides, singlet oxygen, and, most dangerous of all, the hydroxyl radical (symbol •large dot OH ). This potent radical is also generated outside our bodies when radiation hits our cells and damages our DNA. 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 WWII. In the survivors, hydroxyl radicals damaged their DNA innanoseconds.

 Those survivors with good hormone and stem-cell repair systems were able to rebuild and regenerate their bodies and their DNA. 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 factors’ such as IGF-1 and HGH.

I would now like to Explain 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 hundreds of times greater than arsenic, cyanide, and botulism.

 And guess what: we have no natural enzymaticdefenses 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 D.

 Or given a second example, a hydroxyl radical attack occurs on unsaturated fatty acids. This attack generates huge amounts of lipid peroxides in chain reactions. I measured this chain reaction in vivo 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 by 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’sdisease.

 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 ofage.

 

I Now Turn to the Question: 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 all our first line of defense SOD, or superoxide dismutase. In a long series of reactions, SOD renders harmless the superoxide anion radical(symbolO 2•)toordinarywaterandoxygen.

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 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 copperwire.)

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.

 Figure three demonstrates the damaging effects of excessive free radicals in arteries. Experiments in animals have revealed that this powerful superoxide anion radical causes this arterial ischemic damage. Note that these arterial damages are what we have observed in people engaged in very heavy aerobic exercise.

 Figure 3. Before and after photos. 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 damagedarteries.

Photo: Annie Lindbom, Pharmacia. My dear friend professor Karl Ardors at Upjohn-Pharmacia in Sweden performed theseexperiments.

 

 

Second Line of Defense

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. Thus, the resulting arterial damages seen in figure three.

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 thatdied.

 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 line 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 supposedly educated  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, H ₂O ₂ is a weak oxidant.

In contrast, an example of a strong oxidant is chlorine dioxide gas that is generated when sodium hypochlorite is added to our swimming pools or drinkingwater.

 

NaOCl+  ½O₂---------------------- ClO_2(g)

 

Fourth Line of Defense

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 majormechanism

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).

See slide three.

 During aging, we develop increasing and ongoing deficiencies of these two vital anabolics (hGH and 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 hormonedeficiencies.

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:

• Poor gut
• 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

 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). 

OneMayAsk: 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 readily rancid flaxseed oil—we must prevent oxidative damagebygeneratinglargequantitiesoffreshglutathionedaily.

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.

 This method 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. 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.]

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 withC-reactiveprotein,anditisoftenvisiblyapparentasedema.

 Edema causes a puffy appearance, which is seen even in otherwise healthy and athletic people such as Sylvester Stallone and Arnold Schwarzenegger.

 If you doubt these statements, please peruse past and present photos of these two movie stars. You will observe that even though both men are very muscular and athletic, as they were during their younger days, both have acquired facial puffiness 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 escaped their four lines of defense, causing havoc and edema throughout their bodies, 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 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 those synthetic 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 andAging?

 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 of68!

 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 in this slide 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 dl-alpha tocopherol.

 Observe that the right-hand photos 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 11months!

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 correction 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).

I will conclude as Follows:

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 can boost our four lines of defense with supplements such as N-acetyl carnosine, N-acetyl cysteine, ubiquinol, deprenyl, centrophenoxine, l-glutathione, selenium, manganese, zinc, hGH, and IGF-1. Furthermore, we can naturally mitigate consequent inflammation by treatment with omega3s, DHEA, progesterone, polyphenols, curcumin, quercetin, ginger, alpha lipoic acid, and my favorite, Boswellia.

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.

References

1. Lippman,2009, Stay40, Denver, Colorado: Outskirts Press.

2. Sanders, L., June 2009, “Stressed-Out DNA Turns Mousy Brown Hair Gray,” New York Times, New York,

3. Hauer-Jensen, May 2014, FocusMagazine, pp.13-16&21-22. 

4. Ribeiro, M., et al., 2014,“Insulin and IGF-1 improve mitochondrial function in a PI-3K/Akt-dependent manner and reduce mitochondrial generation of reactive oxygen species”, Free Radical Biol. Med. 5849(14), pp.275-265.

5. Misso, NL and Thompson, PJ, 2005, “Oxidative Stress and Antioxidant Deficiencies in Asthma: Potential Modification by Diet,” 10(5), pp.275-255.

6. Higashi Y., et. al., 2013, “Insulin-Like Growth Factor-1 Regulates Glutathione Peroxidase Expression and Activity in Vascular Endothelial Cells: Implications for Atheroprotective Actions of Insulin-Like Growth Factor-1,” Biophys. Acta. 1832, no. 3 (March 2013):391–399.

7. Sukhanov S., et. al., 2007, IGF-1 Reduces Inflammatory Responses, Suppresses Oxidative Stress, and Decreases Atherosclerosis Progression in ApoE-Deficient Mice,” ArteriosclerThrombVascBiol,27(12),2684-2690.

8. Nabet, J.J., 2009, “DHEA L’hormone du mieux- vivre,” Presses du Châtelet, Paris,

9. Private communication, Professor Raj Sohal, head of the Department of biology, Southern Methodist University, Dallas, Texas.

• Sokolove, Michael, June 23, 2011, “For Derek Jeter, on His 37^thBirthday,” New York Times Magazine, New York.