Promoting Mitochondrial Health
By Dale Kiefer
Maintaining healthy mitochondrial function is critically important in preventing disease and promoting longevity. Nutrients such as coenzyme Q10, acetyl-L-carnitine, and alpha-lipoic acid help optimize mitochondrial health. Other nutritional remedies — including carnosine, benfotiamine, and rhodiola — complement the actions of CoQ10, acetyl-L-carnitine, and alpha-lipoic acid in promoting a healthy and energetic lifestyle.
Mitochondria populate the interiors of our cells. These little organelles follow a different drummer when implementing orders from DNA. Unlike other components of the cell, mitochondria have their own DNA.
The mitochondria are genetically exact copies traceable far back into the mists of time. Because human mitochondrial DNA descends through the female alone, it is useful for tracking evolution. In fact, some scientists believe current mitochondrial DNA traces back to a single female known as "Mitochondrial Eve" that eventually climbed all the way up the evolutionary ladder to modern humans.
The Mitochondrial Theory of Aging
Mitochondria literally means "thread granules," a name evidently inspired by the stubby rod-like shape of these organelles. Scattered throughout the jelly-like cytoplasm within our cells, mitochondria range in number from the hundreds to thousands per cell. They generate energy in the form of ATP (adenosine triphosphate)—a molecule that humans literally could not live without. They do so, however, at a price. According to the mitochondrial theory of aging, free electrons are generated as a byproduct of aerobic respiration, which is the chain of ATP-producing chemical reactions that occur within the mitochondria. These electrons convert oxygen to a highly reactive form, which in turn creates still more reactive oxygen species, capable of ravaging proteins and lipids while wreaking havoc with DNA over time. Progressive respiratory chain dysfunction ensues. Damage accumulates slowly, eventually leading to the degenerative changes associated with aging.1-3
Preserving youthful mitochondrial function therefore is of paramount importance to prolonging life span. Fortunately, modern science, often guided by ancient wisdom, is rapidly discovering an ever-increasing arsenal of chemicals and nutrients capable of slowing or reversing many of the degenerative changes constantly occurring within our mitochondria. Nutritional supplements such as acetyl-L-carnitine and lipoic acid have been shown to improve mitochondrial function, protect brain cells, and restore flagging energy.4-8
An acetyl-L-carnitine derivative — acetyl-L-carnitine arginyl amide — has been shown to stimulate brain cells, prompting them to grow new connections to other neurons. This remarkable property suggests an important potential role for this nutrient in combating degeneration of the central nerve system, such as that which occurs because of "normal" senescence. This beneficial derivative of the mitochondrial metabolite acetyl-L-carnitine also protects brain cells from the toxic effects of aggregated amyloid beta peptide. This is especially significant, because amyloid beta is an insoluble protein fragment that forms plaques and induces cell death in the brains of patients with Alzheimer's disease.9,10
Carnosine prevents age-related damage known as glycation, which is responsible for the development of unsightly wrinkles, the corneal opacity of cataracts, and some complications of diabetes, among other things. Natural plant flavonoids such as luteolin favorably modulate immunity and protect against further damage from free radicals.11 Still others, such as benfotiamine and the herb Rhodiola rosea, work in a variety of ways to boost energy, increase endurance, and prevent age-associated changes in cellular processes and structures.
L-Carnitine Metabolites Protect Brain Health
Acetyl-L-carnitine and acetyl-L-carnitine arginate (arginyl amide) may be two of the most potent anti-aging compounds available today. In combination with lipoic acid, they represent the cutting edge of anti-senescence science. Beyond their ability to neutralize damaging free radicals, they act to directly improve brain health through a variety of mechanisms.12
Acetyl-L-carnitine is the ester of a naturally occurring compound, L-carnitine, which serves as an important co-factor in the oxidation of fatty acids within neuronal mitochondria to release energy. L-carnitine deficiencies are associated with a number of serious disorders of the central nervous system.
Conversely, supplementation with L-carnitine metabolites, such as acetyl-L-carnitine and acetyl-L-carnitine arginate, has been shown to improve various brain health parameters. As one researcher recently noted, "... esters such as acetyl-L-carnitine... possess unique neuroprotective, neuromodulatory, and neurotrophic properties which may play an important role in counteracting various disease processes."12
Other Anti-Aging Effects Reported
Acetyl-L-carnitine's benefits are not limited to Alzheimer's patients. In studies of laboratory animals, acetyl-L-carnitine supplementation has demonstrated many dramatic benefits. Aging rats that were fed acetyl-L-carnitine experienced marked increases in levels of tissue carnitine, and significant improvements in age-associated changes in brain lipid composition.17,18 In other animal studies, researchers have reported other dramatic effects, including remarkable increases in physical activity among aging rats fed acetyl-L-carnitine,19,20 improvements in memory,4,21 reversal of age-associated hearing loss,22 and improvements in age-associated glycation of (eye) lens proteins.23
Electron microscopy has shown actual changes in brain mitochondrial structure following acetyl-L-carnitine supplementation.4 Some researchers suggest that acetyl-L-carnitine improves heart function due to its ability to enhance mitochondrial activity. Hard-working cardiac cells that require abundant energy are particularly susceptible to mitochondrial decline.24
In a cleverly designed study, researchers at the FDA's National Center for Toxicological Research showed recently that supplementation with L-carnitine, the precursor to acetyl-L-carnitine, prevents experimentally induced mitochondrial dysfunction in laboratory animals.25 On the other side of the globe, Japanese researchers investigated acetyl-L-carnitine's role in fatigue. In an experiment on human subjects, the researchers determined that serum acetyl-L-carnitine levels are significantly lower among patients with chronic fatigue syndrome than among normal control subjects. The scientists speculated that acetyl-L-carnitine plays an important role in the biosynthesis of neurotransmitters, and that this pathway may be reduced in the brains of chronic fatigue patients.26
Acetyl-L-carnitine's importance to neurotransmitter (brain messenger chemical) production may also underlie the finding that acetyl-L-carnitine supplementation alleviates depression among the elderly.27 Neurotransmitters such as norepinephrine and serotonin are known to play an important role in the regulation of mood, and modern antidepressant drugs operate by increasing the availability of these important brain chemicals.28,29
Acetyl-L-Carnitine Arginate: Unique Benefits
Acetyl-L-carnitine arginate (arginyl amide) exhibits several beneficial properties, especially in the aging brain. Its activities differ from, but also complement, those of acetyl-L-carnitine.
For example, acetyl-L-carnitine arginate appears to mimic the effects of nerve growth factor, a protein that plays a crucial role in the development and maintenance of the nervous system. In the central nervous system (comprising the brain and spinal cord), nerve growth factor supports the survival of neurons in areas of the brain associated with emotion, such as the hippocampus, and in the forebrain, which is associated with cognition, emotion, and important body functions.10
As laboratory rats age, they experience a significant loss of neurons and neuronal activity in these areas. These losses are associated with the degeneration of various physiological functions, and are usually accompanied by deteriorating performance on memory tests. One of the causes of this degeneration may be a reduction in neurotrophic factors, which are supporting factors involved in the nutrition or maintenance of neural tissues, such as nerve growth factor. Since acetyl-L-carnitine has been shown to reverse some of these deficits, Italian researchers reasoned that acetyl-L-carnitine arginate might also improve brain function among aging animals.
To test this hypothesis, they added acetyl-L-carnitine arginyl amide to rat brain cells growing in tissue culture. After ensuring the absence of any native trophic factors, they added acetyl-L-carnitine arginate. The brain cells sprouted new connections—tentative new tendrils of axons and dendrites—known as neurites. The researchers concluded that acetyl-L-carnitine arginate stimulated this remarkable growth by acting directly on receptors for nerve growth factor that are located on the surface of nerve cells.10 This groundbreaking research was later expanded on by researchers at the University of Texas, who experimented on tissue cultures derived from human brain cortex. Their results indicated that acetyl-L-carnitine arginyl amide is indeed neurotrophic.30
Acetyl-L-carnitine arginate's ability to stimulate new growth by neurons is extraordinarily significant. Brain nerve cells, unlike other cells in the body, are generally incapable of repairing themselves. The discovery that acetyl-L-carnitine arginyl amide stimulates new neurite outgrowth suggests an exciting potential treatment for diseases involving neuronal degeneration, such as Alzheimer's disease and Parkinson's disease.
Yet another research team demonstrated that acetyl-L-carnitine arginate protects brain cells from the toxic effects of amyloid beta, the peptide that is believed to trigger cell death when it aggregates in the brains of Alzheimer's sufferers. Using brain cells in culture, the scientists demonstrated that acetyl-L-carnitine arginyl amide "... was able to rescue neurons from [amyloid beta]-induced neuro-toxicity."9
R-Alpha-Lipoic Acid: Potent Antioxidant and More
Acetyl-L-carnitine and lipoic acid could be considered the "dynamic duo" of anti-aging chemicals. Like acetyl-L-carnitine, lipoic acid is a natural mitochondrial metabolite with potent antioxidant properties.5,31 The "R-" form is the most biologically potent form of lipoic acid,32 and numerous studies have paired it with acetyl-L-carnitine to determine the two compounds' synergistic effects on mitochondrial function. All have shown benefits ranging from improvements in memory to increased physical activity levels, improved mitochondrial structure, positive changes in age-related hearing and vision loss, and decreased oxidative damage.5,21,22,23,24
Studies have shown that lipoic acid improves endothelial and heart function, which are important factors influencing cardiovascular health.32-35 Given that aging is the single largest risk factor for cardiovascular disease, and that such diseases are the leading cause of death among people over the age of 65, lipoic acid would appear to be indispensable to anyone of advanced years who wishes to maintain optimal health.33
Like acetyl-L-carnitine, lipoic acid readily crosses the blood-brain barrier, enabling it to benefit neurons and body cells alike. Although it penetrates cell and mitochondrial membranes, it also benefits the extracellular matrix after conversion in the body to a still more potent antioxidant, R-dihydro-lipoic acid. This multitasking molecule possesses the rare ability to function as an antioxidant in both water- and fat-soluble tissues,36 and it is considered an especially potent protector of brain function. As one research team commented, "In-vitro, animal, and preliminary human studies indicate that alpha-lipoate may be effective in numerous neurodegenerative disorders."37
Indeed, exciting new research conducted at Italy's National Cancer Research Institute indicates that lipoic acid may play a role in preventing or reversing the course of neurological disorders such as multiple sclerosis, which involves demyelination, or the destruction of the fatty sheath that insulates neurons.38 Researchers discovered that oral lipoic acid, given before induction of the disease in an animal model, significantly slowed the onset of demyelination. By contrast, destruction of myelin sheathing in brain cells progressed rapidly among control animals that did not receive lipoic acid.38
In the study's second phase, scientists administered lipoic acid only after the disease had been induced. Although oral alpha-lipoate failed to halt the disease's progression, intraperitoneal infusion of lipoic acid significantly curtailed disease progression. (Intraperitoneal means within or administered through the peritoneum, a thin, transparent membrane that lines the walls of the abdominal or peritoneal cavity and encloses abdominal organs such as the stomach and intestines.) The benefit was achieved, researchers noted, independently of lipoic acid's antioxidant activity. In other words, lipoic acid's benefits are not limited to its potent antioxidant activity alone.38
While lipoic acid is a potent antioxidant, it also regenerates the antioxidant capacity of other important antioxidants, such as vitamins C and E. In addition, it boosts levels of the body's important natural antioxidant, glutathione—an especially significant trick. Glutathione is universally recognized as a crucial player in overall health and immunity, but direct supplementation with glutathione offers limited benefit, since it is poorly absorbed when taken orally.36,37 Alpha-lipoic acid (50% R-lipoic acid), on the other hand, is readily absorbed and disseminated throughout the body, and is well tolerated and safe at clinically useful doses of up to 600 mg per day.39-41
Lipoic acid's benefits are numerous. It has been used as a treatment for diabetic neuropathy in Europe for more than 40 years. According to a recently published meta-analysis of double-blind, placebo-controlled studies of patients with diabetic neuropathy, a painful and often debilitating condition: "…treatment with alpha-lipoic acid (600 mg/day i.v.) over 3 weeks is safe and significantly improves... symptoms... to a clinically meaningful degree."39 Additionally, lipoic acid improves glycemic control among type II diabetics, according to recent research on standard and slow-release forms.34,40,42,43 Its combined blood-sugar-lowering and antioxidant effects are believed to account for lipoic acid's multiple benefits.43
Carnosine: Putting the Brakes on Glycation
Aging is a multifactorial process, so fighting back requires a multi-pronged strategy. An invaluable weapon in this battle, carnosine is a dipeptide (two linked amino acids) that occurs naturally in cells. Carnosine is a natural antioxidant and free radical scavenger, but it also tackles another important underlying cause of aging: glycation.
Glycation occurs when protein or DNA molecules chemically bond, or cross-link, with sugar molecules. Eventually the sugars are further modified, forming advanced glycation end products that ultimately cross-link with adjacent proteins, rendering tissue increasingly stiff and inflexible.44 Advanced glycation end products are resistant to the body's routine efforts to remove damaged proteins.
This gradual process plays out in the mirror as we age. Collagen and elastin in the skin lose their suppleness, causing wrinkles to develop, among other changes. However, the damage inflicted by advanced glycation end products does not stop there. Glycation reduces protein flexibility and functionality. It is the culprit behind cataracts, and it plays a role in numerous other degenerative processes, including arthritis, erectile dysfunction, atherosclerosis, kidney disease, and complications of diabetes.45-49
Even worse, advanced glycation end products trigger inflammatory reactions. In the brain, they have been shown to prompt certain cells to generate free radicals and immune system factors, such as chemokines, cytokines, and adhesion molecules, which are ultimately toxic to neurons.50 Many scientists believe that advanced glycation end products play a key role in the development of cognitive decline and Alzheimer's disease. Advanced glycation end products are thought to oxidize tau proteins, which then form the neurofibrillary tangles associated with Alzheimer's disease.51
Fortunately, there is a way to put the brakes on all this glycation damage. Although skeletal muscle levels of carnosine drop by 63% from age 10 to age 70,52 it is possible to augment falling supplies with oral supplementation. Doing so slows or even reverses some of glycation's effects.49,53-55 For instance, when added to living cells growing in culture, carnosine extends the cells' life span. When added to decrepit aged cells, it rejuvenates them.49,54,56
Carnosine's benefits stem from a variety of helpful properties, including its antioxidant capacity. However, it appears to reverse glycation by directly reacting with carbonyl groups that consist of an oxygen atom joined by a double bond with a carbon atom. Alone, these chemical entities are called carbon monoxide. During glycation and oxidation, carbon monoxide attaches to proteins, seriously damaging them and playing an important role in the pathology of advanced glycation end products. Carnosine evidently reacts with these carbonyl groups, altering the defective proteins to which they are attached. This change renders them susceptible to removal by means of ordinary cellular processes.57 Carnosine is nature's multipurpose age-fighter: it scavenges free radicals that cause oxidative damage, inactivates reactive aldehydes and lipid peroxidation products, inhibits glycation, and acts as an endogenous neuroprotective agent.58,59
Diabetes: An Impending Pandemic
According to the American Diabetes Association, diabetes affects about 17 million Americans. Some medical professionals believe this figure may vastly underestimate the true scope of the pandemic. An additional 16-20 million are suspected of having a precursor condition known as pre-diabetes. The legions of people at risk of developing serious diabetic complications swell alarmingly when pre-diabetic patients are included. Taken together, known diabetics and pre-diabetics—collectively described as having "glucose-handling" difficulties— represent a shockingly large percentage of the US population.60
Patients with glucose-handling difficulties are at increased risk of developing life-threatening conditions ranging from heart disease and stroke to blindness, nerve damage, depression, and kidney disease. New evidence suggests that diabetes also takes a toll on the brain, subtly eroding patients' memory and cognition.61,62 These dire secondary complications are the result of excess glucose in the bloodstream, a condition known as hyperglycemia. Although insulin and other medications are used to regulate blood glucose levels as much as possible, damage eventually accumulates. Oscillations in glucose levels are inevitable, even for the most diligent patient.
Benfotiamine Tames Excess Blood Sugar
Until recently, physicians could do little to prevent the dire complications of chronic hyperglycemia. Fortunately, this situation is changing. Exciting research indicates that a nutritional supplement called benfotiamine can block three of the four major metabolic pathways leading to tissue damage. Although it was synthesized in a Japanese laboratory nearly 50 years ago, benfotiamine is only now gaining recognition as a powerful supplement capable of preventing destructive aging effects in the hyperglycemic and alcoholic populations.
Benfotiamine is a slightly altered form of vitamin B1 (thiamine). The alteration renders the vitamin fat soluble, enabling it to access areas of the body that water-soluble thiamine cannot penetrate. This is crucial for controlling potential hyperglycemia-induced damage. Although the problems associated with hyperglycemia are myriad, they all stem from the root problem of glucose flooding into vascular cells and overwhelming their metabolic machinery.
One of the body's proteins, an enzyme called transketolase, blocks the absorption of too much glucose. To do its work, however, transketolase, like many enzymes, requires a co-factor. In this case, it needs assistance from thiamine. Unfortunately, thiamine is water soluble, which makes it less available to cells. Experiments have shown that transketolase's effects are only marginally boosted by the addition of thiamine to cell cultures bathed in excess glucose.63
Used for more than a decade in Germany to successfully treat nerve pain in diabetics, benfotiamine is considerably more available to the body than thiamine. A landmark study, published recently in the medical journal Nature Medicine, found that benfotiamine increases transketolase activity in cell cultures by an astounding 300%. By comparison, when added to cell cultures, thiamine raises transketolase activity a mere 20%. Benfotiamine's robust activation of transketolase was sufficient to block three of the four major metabolic pathways leading to blood vessel damage. Additionally, benfotiamine blocked activation of the pro-inflammatory transcription factor nuclear factor-kappa beta.63
Nuclear factor-kappa beta has been implicated in inflammation, tumor formation, and macular degeneration, as well as retinal disease in diabetics.64,65 It regulates cellular proliferation and suicide. Blocking nuclear factor-kappa beta has been shown to improve the prognosis of arthritis patients.66 These findings suggest still more benefits of benfotiamine therapy.
Rhodiola: A Natural Energy Booster
Rhodiola rosea, also known as golden root or Arctic root, has garnered significant attention in recent years. Although still largely unfamiliar to Westerners, it has been used in traditional medicine for centuries and has been studied extensively by Russian scientists, who have dubbed it an "adaptogen." This term refers to this herb's remarkable ability to increase resistance to numerous chemical, physical, and biological stressors, including strenuous exercise, mental strain, and toxic chemicals.67
Studies have shown that rhodiola enhances exercise endurance, reduces fatigue under stressful conditions, and exerts an anti-inflammatory effect.68-72 Richard Brown, MD, assistant professor of clinical psychiatry at Columbia University and author of The Rhodiola Revolution, recommends it as an energy booster and treatment for depression, chronic fatigue, and anxiety.73
In a randomized, double-blind, placebo-controlled clinical trial on human subjects, Russian researchers showed that rhodiola extract improves the capacity to perform mentally demanding tasks under conditions of excess stress and fatigue. "The study showed a pronounced anti-fatigue effect... [that] was statistically highly significant," the research team concluded.70 A similar controlled trial conducted on students during a "stressful examination period" found that objective and subjective measures of physical and mental performance were significantly superior among subjects who took rhodiola extract compared to those of subjects who took placebo.72
In 2004, Belgian researchers published the results of a randomized, double-blind, placebo-controlled study of rhodiola's effects on endurance exercise performance. They concluded, "Acute rhodiola intake can improve endurance exercise capacity in young healthy volunteers." This effect was not altered by prior daily intake of rhodiola for four weeks.69 It is believed that rhodiola's many beneficial properties stem from its ability to influence the activities and levels of brain chemicals such as serotonin and norepinephrine, as well as of natural "feel good" opioids such as beta-endorphins.67,74
Luteolin Enhances Immune Response
Luteolin is a natural plant flavonoid found in herbs and vegetables, including parsley, olive oil, rosemary, and celery. Among its numerous benefits are modulation of the immune response and neutralization of free radicals.9,75 It has been shown to inhibit immune system chemicals implicated in the development and propagation of allergic disease, including pro-inflammatory interleukin-4 and interleukin-13.75 Likewise, luteolin protects the body from the development of cancer by inhibiting the activation of nuclear transcription factor-kappa beta induced by tumor necrosis factor-alpha, and by sensitizing tumor cells to apoptosis, or programmed cell death.76-78
Luteolin has even been suggested as a treatment for asthma. Indian researchers have shown that luteolin reduces some of the inflammatory processes responsible for the airway constriction associated with asthma.79 Even more interesting, Chinese researchers recently demonstrated that luteolin binds with the surface spike proteins on the deadly virus, blocking its entry into the host cell. In essence, say the researchers, luteolin may represent an effective means of developing new drugs for the prevention of viral infections such as the human immunodeficiency virus (HIV), hepatitis C, and severe acute respiratory syndrome (SARS).80
Wheat Sprout Enzymes: Antioxidant and Antimutagenic
Wheat sprout enzymes are another source of bioactive plant flavonoids. Their potential benefits may range from improving symptoms of fibromyalgia and joint pain to increasing energy and relieving symptoms of chronic fatigue syndrome. These benefits are likely related to the presence of several potent natural antioxidant enzymes, including superoxide dismutase (SOD), glutathione peroxidase, and catalase.
Scientists have known for a number of years that inflammatory diseases are often associated with a decrease in some of these antioxidant enzymes. For example, Korean researchers recently demonstrated that the activity of superoxide dismutase and glutathione peroxidase is significantly lower among rheumatoid arthritis patients than among control subjects. Dietary intake of antioxidants was lower among the arthritis patients than among controls, researchers discovered.81
Their finding echoes conclusions reached by other researchers. Stanford University scientists, for instance, recently reported on the association between the presence of superoxide anion and the development of a wide range of degenerative diseases, including athero- sclerosis, stroke, heart attack, and chronic and acute inflammatory conditions.82 Pro-inflammatory superoxide anion is scavenged and neutralized by superoxide dismutase.
University of Pittsburgh scientists recently noted that overproduction of reactive oxygen species is associated with the development of cardiovascular disease, neurological disorders, and lung pathologies, among other conditions. Superoxide dismutase that operates outside cells, in the extracellular matrix, ". . . is ideally situated to prevent cell and tissue damage initiated by extracellularly produced [reactive oxygen species]," according to the research team.83 More recently, a Texas neuroscience researcher noted that persistent, chronic pain associated with inflammation appears to be mediated by superoxide, and experiments have shown that neutralizing superoxide decreases pain.84
The relationship among superoxide, superoxide dismutase, and disease processes is so compelling that scientists attempted years ago to intervene in diseases such as osteoarthritis by injecting superoxide dismutase derived from livestock blood cells directly into diseased joints. While the relief from inflammation was often dramatic, the technique is somewhat impractical and has not been embraced as a treatment for human patients.85
Soy, corn, and wheat sprouts, on the other hand, may represent a more acceptable means of increasing one's levels of natural antioxidant enzymes. Italian researchers recently published an analysis of the antioxidant content of wheat sprout extract, noting, "catalase and peroxidase activity appears very strong... "86 They also reported, "it is evident that wheat sprout biologically active substances can be at least partially absorbed during the digestion process."86 Another team of Italian scientists compared the antioxidant activity of wheat sprout extract to known pure antioxidants such as ascorbic acid, quercetin, and reduced glutathione. They concluded, "oxygen superoxide scavenging activity performed by wheat sprout extracts... is comparable to that shown by... pure compounds."87
Research has likewise demonstrated that sprout enzymes also possess powerful antimutagenic properties (that is, they prevent mutations that may lead to the development of cancers).88,89 According to unpublished data compiled by researchers at the University of Hawaii, a survey of 120 subjects who ingested large amounts of plant-based antioxidant enzymes revealed that 88% reported increased energy, while 72% reported feeling stronger. Eighty-two percent of survey respondents reported feeling better over all after supplementing with sprout-derived antioxidants.90
Successful aging depends on maintaining a constant, abundant supply of cellular energy. To ensure a continuous supply of energy in the body, it is crucial to support the health of the mitochondria, the power plants of each cell. Nutrients such as lipoic acid and acetyl-L-carnitine have been shown to improve mitochondrial function and boost diminished energy levels. A derivative of acetyl-L-carnitine, acetyl-L-carnitine arginate, has demonstrated additional benefits in supporting brain health and fighting senescence.
Other nutritional and plant-based remedies offer complementary support in the fight against age-related degeneration. Carnosine helps to prevent glycation reactions that are associated with the dysfunction of proteins and enzymes, and can lead to wrinkles, vision changes, and kidney disease. Benfotiamine, a powerful cousin of vitamin B1, helps promote healthy blood glucose levels, a critically important aspect of optimal aging. Plants such as rhodiola, and plant extracts such as luteolin and wheat sprout enzymes, help improve the body's resistance to stressors, relieving fatigue and promoting well being.
Together, these nutrients and plant remedies offer great protection from the wear and tear of time and stress, while supplying the age-defying energy needed for optimal health.
References . . .