Why I Created Invigoral- Chapter 6

How to Reverse Stress Response Damage

Changing health habits related to diet, sleep, exercise, and stress management are difficult in any stage of life. But it is especially true when you are already in the throes of chronic stress. The lack of motivation, mental fog, and low energy levels that usually accompany chronic stress are obstacles that are difficult to surmount without a powerful boost. That’s the purpose of this chapter and the nutrient supplements that will be discussed here.

The particular supplements discussed are those related particularly to the issues associated with the tide of metabolic dysfunction that can accompany chronic stress exposure. Just because certain nutrients are not mentioned doesn’t imply that they aren’t necessary.

Oxidative stress, regardless of the cause, damages cells, tissues, structures, and organs. It is important to maintain antioxidant status with a broad array of different nutrients and supplements. Many of the substances listed below provide antioxidant protection.

 Spiraling Physical and Mental Decline 

This is good, but don’t depend solely upon these as your sole protection. With that said, here’s my “dream team” of supplements that specifically address many of the issues associated with the human stress response and the tide of age-associated problems that are reversible.

Alpha GPC: Boost Memory, Improve Cognitive Function, and Build Muscle

     Please note, that although I site some impressive cognition and memory studies with Alzheimer’s patients who were given Alpha GPC, I am not recommending it as a cure or treatment for pathological dementia. My purpose in referring to these studies is to show this supplement’s effectiveness in improving memory and cognitive abilities. Those with any type of dementia need to be under the care or a physician.

Choline is an essential nutrient and has recently been classified as a new member of the B vitamin complex. Numerous tests with laboratory rats as well as with adults have shown improved memory and recall with the administration of choline. Choline is also quickly depleted with vigorous exercise which can lead to soreness and fatigue. Oral supplementation prior to exercise can help maintain choline levels even after exercise.Most notably, choline helps:

• Maintain healthy cell membranes. Healthy membranes allow nutrients in and waste products out of the cell.

• Promote synthesis of the neurotransmitter acetylcholine. Acetylcholine improves thinking and memory skills. It is also the primary chemical involved in muscular contraction. (Heightened neuronal activity as well as intense physical exertion can deplete acetylcholine stores.)

• Reduce inflammation.

• Temper the stress response.

• Allow more testosterone and less cortisol to be released during physical workouts.

• Maintain normal homocysteine levels. High homocysteine levels are considered to be risk factor in the development of coronary heart disease.

Some researchers consider Alpha GPC (L-Alpha Glycerylphosphorylcholine) to be the best supplemental source of choline available. Not only has Alpha GPC has been shown to boost memory and cognition within 24 hours of taking it, it is also used by body builders, weight trainers, and extreme athletes for its ability to temper post-workout body aches and post-workout physiological stress.

Because Alpha GPC provides a uniquely non-electrically-charged source of choline, it is an invaluable tool for reversing the premature aging tide. Studies show that alpha-GPC increases free plasma choline more quickly than other choline precursors, it promotes synthesis of the neurotransmitter, acetyl  Its lack of charge most likely accounts for its ability to pass over the blood-brain-barrier.

Acetyl-l-carnitine supplementation has long been touted as a valuable way to improve memory  and thinking ability. Clinical trials report that Alpha- GPC is considerably superior to Acetyl-l-carnitine for these purposes. Alzheimer’s subjects treated with alpha-GPC show greater improvement of their general and cognitive conditions than those treated with acetyl-l-carnitine as measured by the universally accepted psychometric and physiologic tests (GGS and SCAGscales).

Three multi-center studies with diagnosed with Multi-Infarct Dementia, compared alpha-GPC with cytidine diphosphocholine. The researchers found Alpha-GPCh to be superior to cytidine diphosphocholine in improving memory, cognitive skills, and behavior parameters. The first study demonstrated that alpha-GPC was significantly superior to cytidine diphosphocholine in improving memory functions. The second study study showed that alpha-GPC provides faster and morecomplete improvement in thinking skills, somatic functioning, memory, and word fluency. In the third study alpha-GPC treatment significantly improved memory, cognitive skills, and behavioral parameters throughout the three-month study. The Alpha-GPCh subjects also showed very high improvement at the follow up examination 30 days beyond the cessation of treatment.

Two clinical trials with a total of 90 subjects with moderately severe age associated memory impairment compared alpha-GPC and Oxiracetam. One trial showed similar, positive results for both agents until the 8th post-treatment follow up week. Positive residual effects of alpha-GPC were consistently better than much better than Oxiracetam with rating scale scores and psychometric tests in the second study.  Alpha-GPC subjects performed  much better than Oxiracetam with rating scale scores and psychometric tests in the second study.

Animal studies suggest daily alpha-GPC use counters neuron loss and memory loss. Researchers report that daily Alpha-GPCh supplementation “counteracts some anatomical changes of the rat hippocampus occurring in old age.” Neurons in the hippocampus relay information to the cerebellum. There are other studies that show alpha-GPCh also helps restore acetylcholine receptor sites. The number of these important sites tends to decrease with age. Amnesia has been directly tied to blocked or decreased levels of acetylcholine. As a result, scientists have used this phenomenon to evaluate the ability of alpha-GPC to reverse this damage. In a recent study the oral administration of alpha-GPC reverses amnesia and partially counteracts the loss of acetylcholine in the brain induced by the drug scopolamine. other study found oral administration of alpha-GPC  actually prevented learning impairment and reversed drug-induced amnesia.

The makers of Alpha-GPCh acknowledge that the phosphatidylcholine component of this product is derived from soybeans. For some, this fact would raise some safety concerns. However, the real concern about soy involves soy protein. The manufacturer’s process that extracts that phosphatidylcholine from the soy bean actually strips out all of the protein. Regular independent lab testing of the product has never detected any soy protein in alpha-GPCh.

Astaxanthin: The Super Anti-Oxidant

Astaxanthin (as-tah-zan-thin) is one of over 600 known carotenoids. Carotenoids are a class of pigments that are usually found in plants, fruits, and vegetables. Not only do these compounds produce distinctive colors—like the orange color of carrots—but many of them also function as antioxidants.

Carotenoids are further divided into carotenes that are comprised solely of carbon and hydrogen atoms (like beta-carotene) and xanthophylls (like astaxanthin) that are contain of carbon, hydrogen, and oxygen.

A primary source for Astaxanthin is environmentally-stressed yeast or algae.

The Astaxanthin I recommend in my practice is produced by the species, hematococcus pluvialis, which is a sea alga. This hematococcus is harvested in ponds in Sweden and is therefore not contaminated with radiation, chemicals or heavy metals.

Astaxanthin’s major benefit is found in it’s incredible antioxidant capabilities. Laboratory analysis of astaxanthin shows that its antioxidant properties are more than 500 times more potent than vitamin E and 10 times stronger than beta-carotene!11 Furthermore, unlike other carotenoids and most antioxidants, even after it neutralizes damaging free radicals, astaxanthin never enters a pro-oxidant state. This means that astaxanthin is invaluable in the fight against oxidative damage, and it will never con tribute to oxidative stress regardless of dose.

Many of the visible signs of aging arise from the cumulative effects of damage from UV light. Potent antioxidants offer great therapeutic and preventive promise by minimizing the oxidative damage from UV light, heavy metals and other matters and elements which pose oxidative threats.

Research performed in Italy, analyzed the ability of various carotenoids to prevent the oxidative damage produced by ultra-violet light (UVA). These researchers found that Astaxanthin was able to provide significant protection against UVA-induced damage. They concluded that Astaxanthin is the most photo-protective carotenoid of all those tested and that it “counteracted all of the studied UVA-induced alterations to a significant extent.”

Additionally, substantial research confirms that astaxanthin supplementation is immensely valuable for ocular (eye) tissues including the retina. The retina loves carotenoids and astaxanthin is the most powerful of the group. Studies show that UV damage to ocular tissue is prevented and even reversed with oral intake and topical application of this unique antioxidant.

Several studies demonstrate astaxanthin’s ability to reduce damage to cellular DNA and protein and to improve mitochondrial function in white blood cells. As mentioned in Chapter Two, glucose-fed mitochondria synthesize the primary energy fuel for the body (adenosine tri-phosphate [ATP]) through a series of chemical reactions. These chemical reactions unavoidably create significant volumes of highly pro-oxidant byproducts (reactive oxygen species [ROS]) that, if not neutralized by antioxidants, increase damaging oxidative stress within the cell.

Laboratory tissue studies show that astaxanthin decreases the oxidative stress generated from normal physiological processes and protects cells from pro-oxidant damage. Studies have also shown that even in very tiny concentrations, astaxanthin is effective in maintaining mitochondrial integrity in the presence of oxidative stress. This finding is extremely significant since oxidative stress leading to mitochondrial dysfunction has a causative link to many diseases, such as cancer, neurodegenerative conditions (such as Alzheimer’s, Parkinsons, and ALS), and other degenerative diseases associated with aging.

Other animal and human studies indicate that axtaxanthin is particularly helpful during and after physical exercise. These results show that it can im prove fat metabolism, 18.19 reduce exercise-induced oxidative stress, 20 improved athletic performance,and reduce muscle damage. Additional research has also show that astaxanthin provides enhanced cognitive and anti-depressant functions, 23 and promote normal blood pressure.

EGCG: Protect Neuronal Tissues, Suppress Glucose Production, and Lower Insulin Resistance

Epigallocatechin gallate (eh-pi-GALL-oh-cat-ah-kin GALL-ate) (EGCG) is a potent antioxidant found in white tea, green tea, and some nuts and vegetables. It is particularly useful in protecting fatty tissues from oxidative stress. Since the brain is approximately 60 percent fat and more susceptible to oxidative damage.

EGCG is an exceptionally valuable nutrient for protecting neurological tissues. In general oxidative damage of fats is at the core of many neurological diseases and cognitive decline. Another phenomenon associated with these maladies is the deposition of certain metals—such as iron and  copper—into brain tissues. Not only is EGCG effective in protection against pro-oxidants, it is also able to chelate (bind and remove) iron and copper in brain tissues.

Several animal studies have demonstrated EGCG’s particular ability to improve and restore cognitive function through its antioxidant activity and other mechanisms as well.  Other research has examined the use of EGCG in other types of neurodegenerative disease with glowing results. Long-term (26 weeks) administration of green tea catechins (EGCG) to rats improved their performance in memory tasks as well as in reduction of cellular pro-oxidants.

EGCG treatment of rats before and after traumaticbrain injury eliminated and/or absorbed free radicals induced by such brain injuries. As a result, neuronal cell degeneration and cell death around the damaged area were inhibited, and brain dysfunction was improved.

EGCG demonstrates helpful activity in animal research involving insulin sensitivity and resistance, carbohydrate metabolism, and even in weight management.  One investigation showed a dramatic improvement in glucose tolerance and weight gain in rats on a high-fat diet.  Another study found that green tea extract, which is high in EGCG, providing balancing help against high serum levels of glucose and cholesterol.

And in a related study that EGCG provides particular antioxidant protections for animals on high cholesterol-high sucrose diets. 37 A recent double blind clinical study also showed that EGCG provided help with compliance to overweight adults on a weight loss diet.

Because of EGCG’s molecular structure and its ability to easily pass through the blood-brain barrier, it provides superior production to brain cells where oxidative stress plays a part in disrupting cognitive function. At the same time it counteracts mitochondrial energy deficit in brain neurons. These protective benefits have also been reported in animal studies involving the liver and kidneys as well as the heart.

Fatigue is an overwhelming sense of tiredness or lack of energy, affecting both mental and physical domains. In a rat model of induced chronic fatigue syndrome, EGCG restored all behavioral and biochemical alterations produced by chronic fatigue.

Phosphatidylserine: Improve Stress Response, Cognitive Function, and Exercise Performance

Phosphatidylserine has been shown to improve recall as well as reduce cortisol levels while under physical or mental stress. While much of the research was on high doses given for a short term (10 days), long term, low dose appears to have similar results; improvement in the stress response and improved memory scores.

In one test, an omega-3 based Phosphatidylserene was administered daily for 6 weeks to eight elderly volunteers who had complained of memory difficulties. At the end of the period researchers reported a 42% increase in recall.   A Japanese study with 73 subjects during a period of 6 months also reported improved memory.

In studies at the University of Whales, adults were given mathematical equations they needed to calculate in a fixed period of time, the group using phosphatidylserine had less perceived stress and a better mood. And, in young adults, with anxiety scores above rather than below the median, the taking of 300mg phosphatidylserine each day for a month was associated with feeling less stressed and having a better mood.

A placebo-controlled trial with 16 subjects demonstrated that phosphatidylserine improved thinking skills and increased brain activity after the subjects were subjected to a stress event.

Several animal studies have demonstrated phosphatidylserine’s ability to improved memory and to combat oxidative stress under a variety of conditions.

In regard to exercise, a double-blind, placebo-controlled, crossover study found that phosphatidylserine “is an effective supplement for combating exercise-induced stress and preventing the physiological deterioration that can accompany too much exercise.

Phosphatidylserine supplementation promotes sired hormonal status for athletes by blunting increases in cortisol levels.”

Other research demonstrates that phosphatidylserine was able to lower exercise-induced cortisol levels by 30%.  In another cyclists study, phosphatidylserine supplementation increased exercise time by an average of 29%.  Other researchers found thatweight trainers at California State University were pushed to over-train reported less muscle soreness and better overall mood when they supplemented with phosphatidylserine.

Resveratrol: A Potential Panacea for Reversing the Tide

Resveratrol was first isolated in 1940 in Japan by a chemist named Michio Takaoka, from white heliebore roots. However, herbal preparations containing resveratrol had been used for centuries in Ayurvedic medical preparation called darakchasava and then in Chinese herbal medicine. It has also been identified as the ingredient in red wine that promotes longevity and reduces risk for cardiovascular disease in the Mediterranean population.

Although the claim about resveratrol sound almost too good to be true, a close look at the research behind it reveals it to truly be an almost magic supplement. Perhaps the quality of resveratrol that has created the most excitement was the discovery that it can actually lengthen chromosomal telemeres. As discussed in Chapter 2, telemeres are the ends on DNA strands that keep them from tangling and thus prevent harmful mutations. Since some researchers suggest that it is the very phenomenon of telemere shortening that is a major cause of aging.

To be fair, there are very few human studies that validate many of the claims that are made concerning resveratrol but there are many promising animal and in vitro studies that, if confirmed in human studies  will be exciting indeed! Resveratrol has been lauded for its ability to:

• Lengthen DNA telemeres

• Neutralize damaging pro-oxidant free radicals

• Activate SIRT genes (SIRT genes are believed to regulate a number of intracellular processes including aging, inflammation, energy use, stress resistance, and insulin sensitivity. They are often dormant in aged cells.)

• Reverse insulin resistance and reduce excessive blood sugar

• Reduce amyloid plaque formations (Amyloid plaques are insoluble fibers that develop because of inappropriately folded protein fragments. When located in brain tissues, they are linked to many neurological and cognitive disorders and diseases.)

• Reduce blood clot risk

• Protect the cells that line arterial walls

• Reduce oxidation of LDL cholesterol

For many years health experts have recommended moderate consumption of red wine for lowering the risk of heart disease. Studies indicate that resveratrol in the wine may be responsible for this observation by reducing the tendency of red blood cells to stick together (platelet aggregation) and by stimulating the production of nitrous oxide which helps to control insulin secretion, peristalsis, neural development, andthe flexibility of cardiovascular tissues.

In a triple-blind, randomized, placebo-controlled clinical trial with a one-year follow-up, 75 stabilized coronary artery disease patients received one of three supplements: 1) 350 mg/day of placebo, 2) resveratrol-containing grape extract, or 3) conventional grape extract lacking resveratrol for 6 months. After 6 months, patients received double dosages of their particular supplement for another 6 months. Changes in circulating biomarkers were analyzed at the end of the testing period and then one year after. The researchers concluded that the grape supplement with resveratrol produced significant cardiovascular benefits.

Animal studies have demonstrated the ability of antioxidant qualities of resveratrol to protect neuronal tissues and skin tissues.

Researchers have demonstrated that dietary supplementation with resveratrol significantly reduced beta amyloid plaque formation in the brains of mice. In the hypothalamus, the part of the brain which controls many of the hormones and activities of the stress response, it reduced these fibrous waste deposits by 90%.  Some have concluded that resveratrol can bind and remove copper, which may be one of the mechanisms involved in amyloid plaques reduction.

Several animal studies have confirmed its ability to protect neurons. Another mechanism that may account for its neuroprotective abilities rests in its anti-diabetic effects.

Other researchers report that resveratrol improves mitochondrial function by activating SIRT1 genes. And other studies that it improves the health and survival of mice on high-calorie diets.

Tocotrienols: The Most Powerful, Almost Secret Form of Vitamin E

For decades vitamin E has been on the short list of “must-take” neuro-protective, antioxidant supplements. Unfortunately, most of the supplements on the market include only one of the eight vitamin E components: alpha tocopherol. The complete vitamin E complex includes alpha, beta, gamma and delta tocopherol (Toe-COUGH-er-ol) and alpha, beta, gamma, and delta tocotrienols (toe-co-TRE-en-ols).

Initially, the major vitamin E research was performed on a synthetic form of alpha tocopherol. One of the probable reasons that a 2008 clinical study found the vitamin E supplementation was not effective in reducing the risk of heart attacks and strokes is that the research employed this incomplete, synthetic form.

Current researcher is reporting that tocotrienols are more potent and exhibit more health benefits than to copherols.  Several studies have found that tocotrienols are much more effective than tocopherols in:

• Reducing cholesterol

• Protecting brain cells against oxidative damage

• Preventing mutations and cancer 76,76,77 • Neutralizing pro-oxidants 78,79,80 • Improves bone density, even       post menopause

Because of their molecular structure, tocotrienols (these have a short unsaturated fatty acid tail) can enter lipid-dense tissues more efficiently than tocopherols (these have a long saturated tail). This is of extreme importance in protecting the brain since it is the organ with the highest percentage of fat.

In a recent double blind study of 232 octogenarians, those with the highest level of all eight vitamin E components the risk of developing Alzheimer’s was reduced by an average of 50% as compared to those with the lowest levels.

Animal research at the University of Wisconsin compared the ability of alpha tocopherol and alpha to cotrienol to neutralize two substances that are known to be toxic to neurons: homocysteic acid and linoleic acid. The researchers found that alpha-tocotrienol, but not alpha-tocopherol, “completely inhibited” homocysteic acid toxicity, thereby “demonstrating increased neuro-protective ability” of alpha-tocotrienol compared to alpha-tocopherol. When looking at linoleic acid toxicity, they found that both alpha-tocotrienol and alpha-tocopherol also “completely inhibited”nerve cell death by linoleic acid when larger doses were used.

Since neurons do not regenerate—when they die, they’re gone forever—I heartily agree with the researchers’ conclusion, that it is prudent to supplement with alpha-tocotrienol to protect neurons from toxic assaults.

One of the risk factors that has become very high profile is high levels of low-density lipoprotein (LDL) cholesterol; often called “the bad cholesterol.” While studies have demonstrated tocotrienols powerful ability to reduce LDL cholesterol there is something far more important: its ability to limit the oxidation of LDL. Oxidized LDL—or any fat for that matter—is much more damaging to health than elevated LDL. In studies examining what it is about cholesterol which increases the risk of atherosclerosis (thickening, hardening or plaque build up) of the arteries, outcomes have shown time and again, it is the oxidation, not the quantity of cholesterol which is the most problematic.

In animal studies where mice were fed cholesterol with and without added tocotrienols, the only mice that did developed atherosclerosis were those that did not receive the tocotrienols.

It should also be noted that the dosage for tocotrienols is very important. Daily intake over 200 to 300 mgs can have an opposite effect and actually damage arterial walls.

Conclusion and Specific Recommendations

The bottom line in regards to staying young, vibrant, and healthy is to keep the stress response and insulin requirements to a minimum. Much of the stress in our lives is unavoidable. The essential key is to reduce the adverse physiological response to that stress by doing the right things.

By taking Alpha GPC along with phosphatidylserine brain cells stay healthier and better able to function, muscles maintain their mass and cortisol levels remain at a minimum. With the addition of resveratrol, EGCG and tocotrienols the cell’s energy factories (mitochondria), maintain their abilities to burn fuel properly and maintaining proper energy production. Resveratrol also promotes longer telomeres, which increases the lifespan of cells while EGCG, astaxanthin and tocotrienols prevent oxidative damage within the cells and of lipids.

So how much of each of these invaluable supplements does one need? Here’s my general recommendation:

• Alpha GPC 300-400 mgs*

• Phosphatidylserine 100-150 mgs*

• Resveratrol 100-150 mgs*

• EGCG 300-400 mgs*

• Astaxanthin 6-10 mgs*

• Tocotrienol 40-50 mgs*

*Please note, these are general recommendation for healthy people who what a boost in managing their stress responses. These recommendations have not been evaluated by the Food and Drug Administration and they are not intended to diagnose, treat, cure or prevent any disease. If you are under the care of a physician for any condition, consult your physician before making any changes to your dietary, exercise, or supplement regimen.


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