A recently published study investigated the effects of curcumin, a constituent of the botanical turmeric, on changes in cognition and memory caused by stress. Chronic stress is increasingly common and known to have numerous adverse health affects. Previous research has shown that curcumin can reverse the chronic stress-induced behavioral changes in mice during an experimental test of the behavior of mice escaping from adverse stimuli.

In this new study, researchers investigated the effect of curcumin supplementation on stress-induced learning defects in mice. More specifically, investigators evaluated stress-induced spatial learning and memory dysfunction in the mice during a water maze task and examined the mechanism in which curcumin affects these stress-related changes.

The results of the study showed that curcumin reversed memory deficits in a dose dependent manner, meaning increasing dosages of curcumin provided increasingly improved memory in the mice. In addition, curcumin reversed the stress-induced increase in the levels of serum corticosterone, the primary hormone secreted during the stress response. The researchers also found that the effectiveness of curcumin was similar to the effects of a tri-cyclic antidepressant.

In addition, the researchers showed that both curcumin and the prescription antidepressant prevented stress-induced changes in the hippocampus, which is the area in the brain that plays an important role in long-term memory and spatial navigation. In fact, both of these treatments inhibited changes due to corticosterone-induced toxicity including preserving nerve cell connections, and inhibiting the corticosterone-induced activation of the enzyme calcium/calmodulin kinase II and stimulated glutamate receptor expression, which play a role in neurotransmitter secretion and certain kinds of memory and learning.

The researchers concluded, “Thus, curcumin may be an effective therapeutic for learning and memory disturbances as was seen within these stress models, and its neuroprotective effect was mediated in part by normalizing the corticosterone response, resulting in down-regulating of the phosphorylated calcium/calmodulin kinase II and glutamate receptor levels.”

Reference:

Xu Y, Lin D, Li S, Li G, Shyamala SG, Barish PA, Vernon MM, Pan J, Ogle WO. Curcumin reverses impaired cognition and neuronal plasticity induced by chronic stress. Neuropharmacology. 2009 Sep;57(4):463-71.

A recently published study investigated the potential benefits of trans-resveratrol in the regulation of antioxidant defense mechanisms in the mitochondria of cells that line the arteries. Resveratrol is a potent antioxidant found in large concentrations in the skin of red grapes and red wine. Mitochondria are the structures inside cells responsible for the generation of cellular energy (ATP). Mitochondrial reactive oxygen species are believed to play a role in the development of complications in diabetic patients. In the United States, an estimated 23.6 million Americans, or 8 percent of the population, have diabetes.

In this new study, researchers evaluated the effect of resveratrol treatment on mitochondrial reactive oxygen species caused by elevated blood sugar (hyperglycemia). Human coronary arterial endothelial cells, which are the cells that line the arteries that provide blood to the heart muscle itself, were cultured and treated with high levels of sugar with or without resveratrol.

The results of the study showed that the cells treated with high levels of glucose had increased levels of mitochondrial reactive oxygen species, which was reversed by the resveratrol treatment. To elucidate the mechanism in which resveratrol provides this activity, the researchers found that the effect of resveratrol is mediated through an enzyme called SIRT1 (Sirtuin 1), which is believed to be one of the intracellular regulatory proteins playing a role in aging, transcription regulation, apoptosis (programmed cell death) and stress resistance.

The study also showed that over-expression of SIRT1 mimicked the effects of resveratrol by attenuating mitochondrial reactive oxygen species production. In addition, resveratrol and SIRT1 over-expression significantly reduced levels of cellular hydrogen peroxide, which are toxic cellular byproducts. Resveratrol and SIRT1 over-expression also up-regulated manganese-superoxide dimutase, a mitochondrial antioxidant enzyme, and increased cellular levels of the potent antioxidant glutathione.

The researchers concluded, “We propose that resveratrol, via a pathway that involves activation of SIRT1 and up-regulation of antioxidant defense mechanisms, attenuates mitochondrial reactive oxygen species production, suggesting the potential for new treatment approaches targeting endothelial mitochondria in metabolic diseases.”

Reference:

Ungvari ZI, Labinskyy N, Mukhopadhyay P, Pinto JT, Bagi Z, Ballabh P, Zhang C, Pacher P, Csiszar A. Resveratrol attenuates mitochondrial oxidative stress in coronary arterial endothelial cells. Am J Physiol Heart Circ Physiol. 2009 Sep 11. Published Online Ahead of Print.

A new study investigated the potential neuro-protective activity of N-acetyl-cysteine (NAC). In the United States, an estimated 5.3 million people have Alzheimer’s disease, and this degenerative disease is currently the seventh-leading cause of death. Alzheimer’s disease is also the most common form of dementia, accounting for 50 to 70 percent of dementia cases with memory loss and decreased intellectual abilities that are serious enough to interfere with daily life.

Alzheimer’s disease is a progressive brain disease in which plaques containing a protein fragment called amyloid beta develop between nerve cells. Additionally, tangles, which contain a protein known as tau, develop inside cells beginning in areas important in learning and memory and then spreading to other regions. Some studies indicate an association between an increased risk of developing Alzheimer’s disease with the intake of metals such as aluminum.

In this new study, investigators examined the effect of NAC in animal models of cognitive dysfunction; specifically, rats were treated with aluminum, a neurotoxin that induced cognitive dysfunction similar to that of Alzheimer’s disease. Previous research indicates that chronic aluminum exposure induces oxidative stress and increases amyloid beta levels. The rats received aluminum treatment or NAC pre-treatment plus aluminum for 6 weeks. During the third and sixth week of the study, the rats were evaluated for both behavioral activities and cognitive function using the Morris water maze and the elevated plus maze task.

The results showed that aluminum administration induced poor retention of memory and increased oxidative damage in the brain. Additionally, aluminum treatment caused a significant increase in acetylcholinesterase activity, which is an enzyme that breaks down the neurotransmitter acetylcholine. Acetylcholine is a chemical in the brain that plays a key role in memory, learning and many other brain functions; significantly, lower levels of acetylcholine are associated with Alzheimer’s disease.

NAC pre-treatment of the rats receiving aluminum treatment resulted in significantly improved memory retention during tasks, decreased oxidative damage and reduced acetylcholinesterase activity.

The study authors concluded, “The study suggests a neuroprotective effect of N-acetyl cysteine against aluminum-induced cognitive dysfunction and oxidative damage.”

Reference:

Prakash A, Kumar A. Effect of N-acetyl cysteine against aluminium-induced cognitive dysfunction and oxidative damage in rats. Basic Clin Pharmacol Toxicol. 2009 Aug;105(2):98-104.

A new study indicates that a popular botanical can help balance lipid levels when used alone or in combination with conventional pharmaceutical treatment. According to the American Heart Association, 106.7 million Americans age 20 and older have elevated levels of total cholesterol.

In this recently published clinical trial, investigators supplemented subjects with yerba maté (Ilex paraguariensis) to evaluate the herb’s potential effects on lipid levels. In this study, 102 subjects were selected including those with normal lipid levels (normolipidemic), subjects with abnormal lipid levels (dyslipidemic) and subjects with elevated cholesterol levels (hypercholesterolemic), who were taking statin drugs. The subjects received 330 mL of green or roasted yerba maté infusions 3 times per day for 40 days.

The results showed that in the subjects with normal lipid levels, yerba maté ingestion reduced the low-density lipoprotein (LDL) cholesterol, commonly referred to as “bad” cholesterol, by 8.7 percent compared to the levels at the beginning of the study. In the subjects with abnormal lipid levels, yerba maté supplementation reduced the LDL cholesterol by 8.1 percent after 20 days and by 8.6 percent after 40 days. In addition, the subjects with dyslipidemia also showed a decrease in apolipoprotein B (ApoB) by 6 percent. ApoB is a component of LDL cholesterol, which is believed to be a better predictor of cardiovascular disease risk than total cholesterol and LDL cholesterol. The dyslipidemic subjects, who drank the yerba maté, also showed an increase of high-density lipoprotein (HDL) cholesterol (the “good” cholesterol) by 4.4 percent.

Additionally, the study found that in the subjects with elevated cholesterol currently taking statin drugs, yerba maté ingestion decreased LDL cholesterol by 10 percent after 20 days and 13.1 percent after 40 days. Also, HDL cholesterol increased by 6.2 percent in this group.

The study authors stated, “It was thus concluded that intake of yerba maté infusion improved the lipid parameters in normolipidemic and dyslipidemic subjects and provided an additional LDL cholesterol reduction in hypercholesterolemic subjects on statin treatment, which may reduce the risk for cardiovascular diseases.”

Reference:

de Morais CE, Stefanuto A, Klein GA, Boaventura BC, de Andrade F, Wazlawik E, Di Pietro PF, Maraschin M, da Silva EL. Consumption of Yerba Mate (Ilex paraguariensis) Improves Serum Lipid Parameters in Healthy Dyslipidemic Subjects and Provides an Additional LDL-Cholesterol Reduction in Individuals on Statin Therapy. J Agric Food Chem. 2009; 57(18):8316-24.

Yerba Maté is found along with other synergistic ingredients in AGEBlock^®.

A recently published study indicated that vitamin E and selenium may provide protection from oxidative damage in experimentally induced colitis. Ulcerative colitis is an inflammatory bowel disorder associated with oxidative damage accompanied by production of free radicals. Inflammatory bowel disease is estimated to affect as many 1.4 million individuals in the United States.

In this new study, rats were treated with acetic acid to induce colitis. Some of the rats were also administered vitamin E 100 mg/kg plus selenium 0.2 mg/kg. Selenium activates the enzyme glutathione peroxidase, which reduces oxidative stress by quenching oxygen free radicals and hydrogen peroxide. The researchers evaluated several measures of oxidative stress in the plasma and colon including total antioxidant capacity, total oxidant status, oxidative stress index and total thiol levels, which are the functional groups of the amino acid cysteine and the antioxidants N-acetyl-cysteine and glutathione. In addition, the researchers measured the activity of several enzymes including catalase, an enzyme which catalyzes the break-down of cytotoxic hydrogen peroxide to water and oxygen; prolidase, which breaks down peptides and proteins with proline or hydroxyproline at one end; and myeloperoxidase, which produces cytotoxic hypochlorous acid and tyrosyl radicals from hydrogen peroxide, and is often measured to determine cellular oxidative stress.

The results showed that acetic acid treatment induced inflammatory damage in the rat colon. Selenium and vitamin E treatment decreased both visible and microscopic damage in the colon caused by acetic acid. Additionally, acetic acid treatment increased the activity of myeloperoxidase as well as increased the total oxidant status and oxidative stress index in the plasma, and decreased total antioxidant capacity and total thiol levels in the colon. Treatment with vitamin E and selenium decreased myeloperoxidase activity, increased total antioxidant capacity and increased total thiol levels in the colon.

The authors stated, “Based upon these results, selenium and vitamin E may play an important role in preventive indication of the oxidative damage associated by acetic acid caused inflammation.”

Reference:

Bitiren M, Karakilcik AZ, Zerin M, Ozardali I, Selek S, Nazligül Y, Ozgonul A, Musa D, Uzunkoy A. Protective Effects of Selenium and Vitamin E Combination on Experimental Colitis in Blood Plasma and Colon of Rats. Biol Trace Elem Res. 2009 Sep 23. Published Online Ahead of Print.

A recently published study analyzed the importance of vitamin K in short-term survival as well as for long-term health and chronic disease. The researchers were investigating a theory known as the triage theory, which suggests that during a shortage of micronutrients in the body, the micronutrients are used for physiological functions required for short-term survival over those that are related to long-term health and age-related diseases including osteoporosis, atherosclerosis, and cancer.

In this study, researchers evaluated 11 vitamin-K-dependent proteins in mice to establish the effect of the functional status of each of these proteins on survival. Five of the proteins were required for blood clotting. The researchers also investigated the vitamin-K-dependent proteins osteocalcin, a protein that plays a role in bone mineralization and calcium metabolism; matrix Gla protein, a calcium-binding protein that is involved in the organization of bone tissue; growth arrest specific protein 6, a protein thought to be involved in the stimulation of cell proliferation; transforming growth factor beta-inducible protein, which controls proliferation and cellular differentiation and plays a role in immunity, cancer, heart disease, and diabetes; and periostin, a protein important for bone growth and heart cell regeneration.

The results of the study showed that the 5 vitamin-K-dependent proteins required for blood clotting were lethal when non-functional. The mice missing any of the other proteins survived until weaning, suggesting those proteins were less critical for survival.

The researchers further discuss the consequences of dietary vitamin K inadequacy and vitamin K deficiency induced by chronic anticoagulant (warfarin/Coumadin^®) therapy, which are all linked to age-associated conditions including: 1) bone fragility after estrogen loss, which is related to osteocalcin; 2) arterial calcification linked to cardiovascular disease, which is related to matrix Gla protein; and 3) increased spontaneous cancer in mice without functional transforming growth factor beta-inducible protein.

The study authors stated, “A triage perspective reinforces recommendations of some experts that much of the population and warfarin/Coumadin patients may not receive sufficient vitamin K for optimal function of vitamin-K-dependent proteins that are important to maintain long-term health.”

Reference:

McCann JC, Ames BN. Vitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging? Am J Clin Nutr. 2009 Oct;90(4):889-907.

A new study revealed that a potent antioxidant can improve immune dysfunction and oxidative stress caused by a high-fat diet.

In the United States, the average daily intake of trans-fat is approximately 5.8 grams, with saturated fat constituting approximately 11-12 percent of the diet. Additionally, fast food meals total approximately 55 percent of the diet for the average American. High-fat diets have been linked to immune dysfunction, including diminished numbers and function of white blood cells known as lymphocytes, increased susceptibility to infection and the development of oxidative stress, which damages cells.

In this new study, researchers investigated the mechanism in which high-fat diets suppress lymphocyte function in mice. The researchers evaluated the gene expression from lymphocytes in the small intestines to understand the role of oxidative stress in lymphocyte signaling. The study also evaluated the effect of the antioxidant lipoic acid on these changes. Lipoic acid is a unique antioxidant in that it is both fat and water soluble, and can regenerate other antioxidants such as glutathione, vitamin C and vitamin E.

The results of the study confirmed that a high-fat diet induced oxidative stress and immune suppression in the small intestine. Treatment with lipoic acid reversed the high-fat-diet-induced immune suppression and reduced the oxidative stress. Specifically, lipoic acid was shown to improve the transcription of genes important for B-lymphocyte receptors, which are receptors for white blood cells that mature in the bone marrow, as well as T-lymphocyte differentiation and free radical scavenging mechanisms.

The researchers stated, “The present study indicates that a high-fat diet can induce chronic oxidative stress, suppress signal transduction of gut-associated lymphocytes, and lead to an inhibition of mucosal immunity.”

Reference:

Cui J, Le G, Yang R, Shi Y. Lipoic acid attenuates high fat diet-induced chronic oxidative stress and immunosuppression in mice jejunum: A microarray analysis. Cell Immunol. 2009 Aug 11. Published Online Ahead of Print.

Glutathione is known to be a critical component of both the antioxidant and detoxification systems.

Glutathione is a tripeptide, a naturally occurring protein that is composed of three amino acids: glycine, glutamine and cysteine. It is made by every cell in the human body and it plays a part in the function of every cell in the body. Glutathione also contains a sulfur molecule. Sulfur plays a major role in glutathione’s antioxidant and detoxification functions, and it also gives glutathione its distinctive sulfurous aroma.

Powerful Antioxidant

While vitamin C and vitamin E are better known, the ability of glutathione to work with enzymes makes it the more reliable antioxidant workhorse for the human antioxidant system. When nutrients are discussed, the topic of oxidative stress frequently comes up. Oxidative stress refers to the changes that occur in the biochemistry of molecules in the body when they interact with oxygen. In the outside world oxidative stress shows up as rust. Inside the body, oxidative stress is harder to visualize, but it causes damage to cells and the membranes of cells.

Without adequate glutathione function, oxygen metabolism in the energy producing sites in the cell called mitochondria can form an increased number of free radicals. Free radicals are electron “hungry” and will pull electrons from surrounding structures such as proteins or membranes, causing them to stop functioning normally. When this happens it is called “free radical damage,” which will cause a decrease in the function of the cell. Free radicals must be neutralized or this “rust” will cause cells to perform poorly or die. Accumulation of damage to cells leads to problems in entire organs and eventually disease. Illnesses such as the Chronic Fatigue Syndrome may be related to decreased energy production from individual cells.¹¹

Glutathione is one of the major defenders against oxidative stress. In its “reduced” (active) form it can donate an electron and behave as an antioxidant. After losing an electron, it becomes non-functional, or “oxidized.” The ratio of reduced to oxidized glutathione in cells is a measure of oxidative stress. Studies have shown that oxidative stress increases with aging and it is no wonder that over time free radicals can lead to degenerative diseases: heart disease, memory problems, cancer, diabetes, arthritis.

The discovery and path of understanding of glutathione began in 1888, culminating in 1926 when its structure was finally determined.^1-2 Glutathione is so important to the utilization of oxygen in our bodies that is difficult to write about oxidative stress without mentioning it, so glutathione shows up often in the scientific literature. In 1999 a single-word search on glutathione pointed out that 40,000 articles were found in the government library under the search term “glutathione.”³ In the past ten years, this number has more than doubled and is now over 87,000 references. The numbers of research articles show that research into the role that glutathione plays in maintaining cell function is ongoing and important.

In certain disease conditions, glutathione does not get manufactured as efficiently as needed. The lack of glutathione can result in disease conditions from a systemic decrease as we see in atherosclerosis. Glutathione can also be deficient in local tissues as has been shown with asthma.⁴ In situations where there is a lot of oxidative stress, as occurs in diabetes that is not well controlled, glutathione is not formed and becomes deficient even when the building block amino acids such as cysteine are abundantly available.⁵

The Great Detoxifier

Glutathione is also known as a detoxifying agent. Most toxins are able to pass through fatty membranes, so they tend to accumulate inside of cells. Binding toxins with glutathione makes the combination water soluble and allows its removal.

The liver harbors the most concentrated source of glutathione because it is the organ of detoxification. Your body uses glutathione to protect you from pollution, radiation, drugs, carcinogenic chemicals and heavy metals. Modern living even exposes us to toxins in our water and food. Dealing with this onslaught is especially difficult for people with certain neurological conditions such as autism, because they have difficulty ridding their bodies of toxins.

Glutathione has the ability to bind with toxins directly, especially if the correct type of matchmaker enzyme is present. About 10-30 percent of the population will not have this enzyme that enhances glutathione function,⁷ and in these cases increasing the presence of glutathione may help increase the chance of a GSH molecule matching up with a toxin.

Toxins such as mercury are removed from the body by direct conjugation with glutathione.⁸

Glutathione can attach to metals and other toxins directly and there is an extensive list of biochemicals that can be bound to glutathione.⁹ Once bound to glutathione, toxins become water soluble and can be transported out of the cell and out through the liver for excretion. Maintaining normal bowel flora and a high-fiber diet is important during detoxification to prevent the reabsorption of toxins like methyl mercury from the bowel.¹⁰ Other toxins, such as those produced from molds or fungus called mycotoxins have also been shown to cause an increase in oxidative stress and will also deplete glutathione. With all the roles that glutathione plays, it is easy to see why there are so many articles written about glutathione in the medical science literature.

Glutathione and Disease

We have already mentioned several health conditions in which glutathione plays a role. In addition, studies have shown that alcoholics have low glutathione and so do people with Alzheimer’s disease. Cigarette smoking depletes glutathione, and children with autism are predisposed to low glutathione so they cannot detoxify normally. Glutathione is suggested as a promising treatment to combat the oxidative stress found in HIV-infected people. Long-lived women have high levels of glutathione, and people with Parkinson’s disease often benefit from treatment with glutathione. It also is posited that the oxidative stress that depletes cells of glutathione increases vulnerability to influenza.

Because heart muscle requires a lot of energy for its continual function, it has the largest number of mitochondria per cell of any tissue in the body. It would be logical to expect that glutathione is also needed in the heart muscle cells to maintain function. It turns out that studies have shown that a deficiency of glutathione is correlated with the recurrence of heart problems after heart attacks.¹² It has also been shown that low glutathione is associated with the progression of coronary artery disease even in healthy adults.¹³

Liposomal Glutathione

Recent developments with a liposomal form of glutathione suggest that wrapping glutathione in a tiny lipid bubble called a liposome is an excellent way to keep glutathione stable and make it available for use in cells.⁶ A liposome is an extremely small (1/2 the width of a human hair) bubble, which is also called a vesicle. Liposomes have a fat-soluble exterior and an interior that is watery. This watery interior can combine with water soluble materials such as glutathione.

Liposomes are made from the same type of material as our cell membranes, phospholipids. Because they are made of the same type of material as our cell membranes, liposomes penetrate mucosal tissues allowing for rapid release into the blood stream. Nutrients that are not in liposomes have to pass through the stomach to reach the liver where they are metabolized and released into the bloodstream. Some nutrients are destroyed or compromised by stomach acids. Liposomes avoid the digestive system by penetrating the mucosal tissue.

Laboratory testing shows that the liposome can maintain glutathione in the biochemical “reduced” state, the state that means it is active and can donate an electron as an antioxidant. In an animal study, Liposomal Glutathione was able to maintain the function of glutathione allowing the scavenger cells to metabolize cholesterol and slow the deposition and progression of plaque in the arteries.¹⁴ Further studies will be needed before a definitive statement about the role that glutathione plays in maintaining normal function in the cells lining arteries can be made.

LipoCeutical^™ Glutathione, now available here as a dietary supplement, is a promising way to obtain a crucial antioxidant that has a wide role to play in health.

References

1. Simoni RD, Hill RL, Vaughan M. On glutathione. II. A thermostable oxidation-reduction system (Hopkins, F. G., and Dixon, M. (1922) J. Biol. Chem. 54, 527-563). The Journal of biological chemistry. 2002;277(24):e13.

2. Meister A. On the discovery of glutathione. Trends in biochemical sciences. 1988;13(5):185-8.

3. Sies H. Glutathione and its role in cellular functions. Free radical biology & medicine. 1999;27(9-10):916-21.

4. Fitzpatrick AM, Teague WG, Holguin F, Yeh M, Brown LA. Airway glutathione homeostasis is altered in children with severe asthma: evidence for oxidant stress. The Journal of allergy and clinical immunology. 2009;123(1):146-52 e8.

5. Darmaun D, Smith SD, Sweeten S, Hartman BK, Welch S, Mauras N. Poorly controlled type 1 diabetes is associated with altered glutathione homeostasis in adolescents: apparent resistance to N-acetylcysteine supplementation. Pediatric diabetes. 2008;9(6):577-82.

6. Zeevalk G, Guilford F, Bernard L. Liposomal glutathione for replenishment and maintenance of intracellular glutathione in mesencephalic cultures. Abstract Neuroscience 2009: Soc. for Neuroscience 2009.

7. Kempkes M, Golka K, Reich S, Reckwitz T, Bolt HM. Glutathione S-transferase GSTM1 and GSTT1 null genotypes as potential risk factors for urothelial cancer of the bladder. Archives of toxicology. 1996;71(1-2):123-6.

8. Clarkson TW, Vyas JB, Ballatori N. Mechanisms of mercury disposition in the body. Am J Ind Med. 2007;50(10):757-64.

9. Ballatori N, Krance SM, Notenboom S, Shi S, Tieu K, Hammond CL. Glutathione dysregulation and the etiology and progression of human diseases. Biological chemistry. 2009.

10. Rowland IR, Mallett AK, Flynn J, Hargreaves RJ. The effect of various dietary fibres on tissue concentration and chemical form of mercury after methylmercury exposure in mice. Archives of toxicology. 1986;59(2):94-8.

11. Myhill S, Booth NE, McLaren-Howard J. Chronic fatigue syndrome and mitochondrial dysfunction. International journal of clinical and experimental medicine. 2009;2(1):1-16.

12. De Chiara B, Mafrici A, Campolo J, Famoso G, Sedda V, Parolini M, et al. Low plasma glutathione levels after reperfused acute myocardial infarction are associated with late cardiac events. Coron Artery Dis. 2007;18(2):77-82.

13. Ashfaq S, Abramson JL, Jones DP, Rhodes SD, Weintraub WS, Hooper WC, et al. The relationship between plasma levels of oxidized and reduced thiols and early atherosclerosis in healthy adults. Journal of the American College of Cardiology. 2006;47(5):1005-11.

14. Rosenblat M, Volkova N, Coleman R, Aviram M. Anti-oxidant and anti-atherogenic properties of liposomal glutathione: studies in vitro, and in the atherosclerotic apolipoprotein E-deficient mice. Atherosclerosis. 2007;195(2):e61-8.

Last month, I began a three-part series about how stress affects the human body with the introductory article focusing on the effect that stress has on cognition and memory. In part two of this series I will explain how stress can impair proper digestion leading to constipation, diarrhea, irritable bowel syndrome and other digestive disorders.

Like all systems of the human body, the gastrointestinal tract does not operate independently. Its proper functioning depends upon other aspects of the human body. Because gastrointestinal function is controlled and coordinated by the central nervous system to ensure effective motility, secretion, absorption and mucosal immunity,¹ it’s logical that emotional stress can have a huge impact on colon health—especially considering the highest amount of serotonin, the neurotransmitter most commonly associated with happiness, resides in our GI tract. Furthermore, during the holidays, a time when we already are exposed to additional amounts of GI-impairing emotional stress, we are further burdening our digestive tracts by consuming large amounts of sugary treats and refined carbohydrates. In this article I will offer some suggestions on how one can strengthen digestive health at this time of year and beyond.

The connection between the gut and emotional health is evidenced by the fact that improving the health of the gut can also improve emotional well being. The absence of probiotic bacteria in the gut has been shown to not only impair colonic health but also to affect the functioning of the hypothalamic-pituitary-adrenal axis and monoaminergic activity, features that have been implicated in the origins of depression. In one study, researchers evaluated the potential antidepressant properties of probiotics, by giving rats the probiotic Bifidobacteria infantis then exposing the animals to a forced swim test in order to stress the animals. The study authors also assessed the effects of the probiotic on immune, neuroendocrine and central monoaminergic activity. After being treated for 14 days with B. infantis, the rats’ swim behaviors did not change. However, the probiotic significantly reduced pro-inflammatory immune responses including IFN-gamma, TNF-alpha and IL-6 cytokines. Furthermore, there was a marked increase in plasma concentrations of tryptophan (an amino acid and serotonin precursor known for its relaxation properties) in the bifidobacteria-treated rats when compared to controls.² The researchers concluded that the preliminary findings provide “encouraging evidence in support of the proposition that this probiotic may possess antidepressant properties.”

The worsening of irritable bowel syndrome also has been linked to stress. In a study of 105 subjects with mild IBS (68 of the diarrhea-predominant type and 37 of the constipation-predominant type), subjects were followed for three years. During this time, there was a worsening of IBS in 37 subjects. The researchers linked seven factors as being predictive of the onset of full-blown IBS including exposure to emotional stressors, two kinds of stress-coping styles, eating habits, sleeping time and psychological abuse.³

Levels of the stress hormone cortisol also have been found to be elevated in irritable bowel syndrome patients⁴ and a faster resolution of cortisol to basal values corresponds to lower symptom-severity.⁵ Additionally, psychological distress and GI symptoms are related to the severity of bloating in women with irritable bowel syndrome.⁶ Stress also appears to damage the gastrointestinal tracts of individuals not suffering from outright bowel diseases. In healthy individuals, disrupted cortisol levels have been linked to the development of diarrhea.⁷

Recent well-designed studies have confirmed that adverse life events, chronic stress and depression increase the likelihood of relapse in patients with quiescent IBD. This evidence is increasingly supported by studies of experimental stress in animal models of colitis. In animal models of colitis, psychological or environmental stress may increase gastrointestinal permeability, allowing abnormal antigen to be presented to the immune system and leading to the worsening of intestinal inflammation. The increased intestinal permeability under stress is controlled by corticotropin-releasing hormone stimulation through nicotinic, adrenergic and cholinergic receptors, suggesting a complex interplay between sympathetic and parasympathetic nervous systems.^8-9

Chronic stress may have a role to play in the inflammation that occurs in Crohn’s disease (CD), a chronic inflammatory condition of the gastrointestinal tract, whose etiology involves genetic, psychological, immune and inflammatory factors. A higher prevalence of psychological disorders has been observed in CD patients and studies show that there may be a relationship between psychological stress and CD, controlled by the hypothalamic-pituitary-adrenal and the hypothalamic-autonomic nervous system axes.¹⁰

Protecting the GI Tract from Stress

Protecting the digestive tract during times of psychological stress is important at any time of year. But during the holiday season, when we are under increased stress and consuming an excess of sugary, rich foods, protecting the GI tract is more important than ever. Protecting the health of the colon with GI Cell Support, Lectin Lock^™, BioPRO^™ and Digestive Enzymes can be an effective approach to improving GI integrity during times of stress.

GI Cell Support

Glutamine, DGL, N-Acetyl-Glucosamine, Marshmallow, Berberine, Cabbage, Slippery Elm, Phosphatidylcholine and Gamma Oryzanol (all found in GI Cell Support) work together to strengthen the health of the GI Tract. Glutamine, the most abundant free amino acid in the body, is critical for maintaining intestinal structure. The GI tract has the largest demand for glutamine in the body.¹¹ Human studies have shown that supplemental glutamine can reduce the chemotherapy-induced increase in intestinal permeability¹² and decrease the duration of diarrhea in children.¹³ In animal studies, supplemental glutamine promoted repair of intestinal mucosa after chronic diarrhea.¹⁴

Other important GI-healing substances include:

• Deglycyrrhizinated licorice (DGL), which seems to be similar to carbenoxolone, a semisynthetic derivative of glycyrrhetic acid used outside the US for treating gastric and duodenal ulcer disease.^15-16 Clinically, DGL demonstrates great utility in lessening intestinal irritation and related symptoms.

• N-Acetyl-Glucosamine, which has been found to be deficient in inflammatory bowel disease (IBD), reducing the synthesis of the gastric and intestinal mucosa’s protective glycoprotein cover.¹⁷

• Marshmallow, which contains mucilage polysaccharides that soothe and protect mucous membranes from local irritation by creating a protective layer.^18-19

• Berberine, which helps control inflammation in the GI tract by selectively inhibiting cyclooxygenase (COX)-2 expression and blocking proinflammatory cytokines.²⁰

• Cabbage, which lowers the risk of developing stomach and colorectal cancer²¹ and raw cabbage juice consumed by 100 peptic ulcer patients dramatically reduced pain, and significantly reduced healing time.²²

• Slippery Elm preparations, which trigger gentle stimulation of nerve endings in the GI tract, leading to mucous secretion that coats and protects the delicate lining of the intestines from ulcers, excess acidity, ingested irritants and toxins.^23-24

• Phosphatidylcholine, which was shown in a randomized, double-blind, placebo-controlled study of patients with ulcerative colitis to be low in the colonic mucus of these patients. These low phosphatidylcholine levels are a likely contributory factor involved in the development of ulcerative colitis.²⁵

• Gamma oryzanol, which is highly regarded in Japan to promote a healthy gastrointestinal environment. In animal models, it appears to modulate pituitary secretion, and inhibit excess gastric acid secretion and platelet aggregation.²⁶

Blocking Lectins

Lectins are a class of proteins found in common foods, especially grains, seeds, beans, nuts, some fruits and vegetables and seafood. They act as a sort of an immune system for plants by “sticking” themselves to the structural carbohydrates (sugars) of invaders. When we eat foods containing these proteins we risk lectin attachments to the structural carbohydrates (sugars) antigens found in the gut and immune system. Lectin attacks in the gut initiate inflammation that may be expressed in other parts of the body. Lectins from the diet damage the delicate intestinal lining (the microvilli) and negatively influence gut permeability (leaky gut) and protein digestion. Lectins contribute to food sensitivities (or food intolerances) and may provoke the immune system to make antibodies against them. IBS, for example, is a symptom of lectin-related food intolerances.

Genetic individuality determines our recognition of food as friend or foe and it is not based on the nutritional value of a food. For example, tomatoes contain lycopene, an important antioxidant, but tomatoes also contain a panhemagglutinin lectin (Lycopersicon esculentum agglutinin) that is not harmless. It lowers mucin, binds to blood cells, nerve tissue, and interferes with gastrin in the stomach creating problems in susceptible people.^27-28 (Consider watermelon, guava and red grapefruit or a supplement to consume adequate amounts of lycopene.) The same is true of many foods. Foods like corn, dairy, chicken, peas, bananas, beans and legumes, soy, potatoes, pomegranate, nuts, cantaloupe, seafood, wheat, millet and many more, although they contain a variety of very healthful nutrients, contain potentially harmful lectins that can cause problems in some people.

Consuming a combination of lectin-blocking ingredients such as N-acetylglucosamine (NAG), bladderwrack, Okra, D-mannose and sodium alginate (all found in Lectin Lock) can protect the colon against the onslaught of lectin-containing foods we are exposed to during holiday gatherings and all year long.^29-34

Digestive Enzymes

Each of the five main digestive enzymes has a different role to play. Amylase digests starch. Protease breaks down the peptide bonds that join the amino acids in a protein, ensuring the amino acids are readily available to the body. The enzyme lipase splits apart emulsified fats. Lactase digests milk sugar, while cellulase helps break down plant and vegetable matter. These enzymes are secreted by the pancreas and are often referred to as pancreatic enzymes. Deficiencies of these enzymes can wreak havoc on the digestive tract, causing bloating, flatulence and gastrointestinal discomfort.^35-37 Without proper supplies of these enzymes, the body struggles to digest the high-fat or high-starch meals frequently consumed during the holidays.

Vitamin Research Products’ Digestive Enzymes is a unique, plant-based formula containing amylase, protease, lactase, lipase and cellulase. The vegetarian enzymes are generally better tolerated than animal-derived enzymes as a source of nourishment for the intestinal tract.

Friendly Flora

As mentioned earlier in this article, probiotic bacteria are linked to both GI health and mental well being. The “good” bacteria Bifidobacteria infantis has been found to have anti-depressant properties in animals under stress.² Furthermore, strains of Lactobacillus acidophilus and Bifidobacterium longum have been tested in humans experiencing stress-induced gastrointestinal symptoms. In the double-blind, placebo-controlled, randomized study conducted on volunteers with symptoms of stress, subjects received a probiotic-containing Lactobacillus acidophilus and Bifidobacterium longum or a placebo without probiotics for three weeks. The consumption of probiotics significantly reduced 2 stress-induced gastrointestinal symptoms (abdominal pain and nausea/vomiting).³⁸

Bifidobacteria infantis, Lactobacillus acidophilus and Bifidobacterium longum are all found in BioPRO.

Conclusion

The gastrointestinal tract is especially vulnerable to psychological stress, but never more so than during the holidays when it is being subjected to an array of unhealthy foods. Supplementing with nutrients shown to heal the GI tract, lectin-blocking nutrients, digestive enzymes and a good probiotic formula will strengthen the digestive system and provide it with an overall foundation of health during the holidays and throughout the year.

References

1. Verdu EF. Probiotics effects on gastrointestinal function: beyond the gut? Neurogastroenterol Motil. 2009 May;21(5):477-80.

2. Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG. The probiotic Bifidobacteria infantis: An assessment of potential antidepressant properties in the rat. J Psychiatr Res. 2008 Dec;43(2):164-74.

3. Fujii Y, Nomura S. A prospective study of the psychobehavioral factors responsible for a change from non-patient irritable bowel syndrome to IBS patient status. Biopsychosoc Med. 2008 Sep 25;2:16.

4. Chang L, Sundaresh S, Elliott J, Anton PA, Baldi P, Licudine A, Mayer M, Vuong T, Hirano M, Naliboff BD, Ameen VZ, Mayer EA. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in irritable bowel syndrome. Neurogastroenterol Motil. 2009 Feb;21(2):149-59.

5. Videlock E, Adeyemo M, Licudine A, Hirano M, Ohning G, Mayer M, Mayer E, Chang L. Childhood trauma is associated with hypothalamic-pituitary-adrenal (HPA) axis responsiveness in irritable bowel syndrome. Gastroenterology. 2009 Sep 5. Published online ahead of print.

6. Park HJ, Jarrett M, Cain K, Heitkemper M. Psychological distress and GI symptoms are related to severity of bloating in women with irritable bowel syndrome. Res Nurs Health. 2008 Apr;31(2):98-107.

7. Karling P, Norrback KF, Adolfsson R, Danielsson A. Gastrointestinal symptoms are associated with hypothalamic-pituitary-adrenal axis suppression in healthy individuals. Scand J Gastroenterol. 2007 Nov;42(11):1294-301.

8. Mawdsley JE, Rampton DS. Psychological stress in IBD: new insights into pathogenic and therapeutic implications. Gut. 2005 Oct;54(10):1481-91.

9. Stasi C, Orlandelli E. Role of the brain-gut axis in the pathophysiology of Crohn’s disease. Dig Dis. 2008;26(2):156-66.

10. Stasi C, Orlandelli E. Role of the brain-gut axis in the pathophysiology of Crohn’s disease. Dig Dis. 2008;26(2):156-66.

11. Miller AL. Therapeutic considerations of L-glutamine: a review of the literature. Altern Med Rev. 1999;4:239-48.

12. Li Y, Yu Z, Liu F, Tan L, Wu B, Li J. Oral glutamine ameliorates chemotherapy-induced changes of intestinal permeability and does not interfere with the antitumor effect of chemotherapy in patients with breast cancer: a prospective randomized trial. Tumori. 2006 Sep-Oct;92(5):396-401.

13. Yalçin SS, Yurdakök K, Tezcan I, Oner L. Effect of glutamine supplementation on diarrhea, interleukin-8 and secretory immunoglobulin A in children with acute diarrhea. J Pediatr Gastroenterol Nutr. 2004 May;38(5):494-501.

14. Huang ZX, Ye LY, Zheng ZY, Chen XM, Ren RN, Tong GY. [Effect of glutamine on small intestinal repair in weanling rats after chronic diarrhea]. Zhonghua Er Ke Za Zhi. 2005 May;43(5):368-72.

15. van Marle J, Aarsen PN, Lind A, van Weeren-Kramer J. Deglycyrrhizinised liquorice (DGL) and the renewal of rat stomach epithelium. Eur J Pharmacol. 1981;72:219-25.

16. Tewari SN, Wilson AK. Deglycyrrhizinated liquorice in duodenal ulcer. Practitioner. 1973;210:820-3.

17. Burton AF, Anderson FH. Decreased incorporation of 14C-glucosamine relative to 3H-N-acetyl glucosamine in the intestinal mucosa of patients with inflammatory bowel disease. Am J Gastroenterol.1983;78:19-22.

18. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.

19. Martindale W. Martindale the Extra Pharmacopoeia. Pharmaceutical Press, 1999.

20. Fukuda K, Hibiya Y, Mutoh M, et al. Inhibition by berberine of cyclooxygenase-2 transcriptional activity in human colon cancer cells. J Ethnopharmacol. 1999;66:227-33.

21. van Poppel G, Verhoeven DT, Verhagen H, Goldbohm RA. Brassica vegetables and cancer prevention. Epidemiology and mechanisms. Adv Exp Med Biol. 1999;472:159-68.

22. Cheney G. “Vitamin U Therapy of Peptic Ulcer”. California Medicine. 1952;77(4): 248-252.

23. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.

24. Gruenwald J, Brendler T, Jaenicke C. PDR for Herbal Medicines. 1st ed. Montvale, NJ: Medical Economics Company, Inc., 1998.

25. Stremmel W, Ehehalt R, Autschbach F, Karner M. Phosphatidylcholine for steroid-refractory chronic ulcerative colitis: a randomized trial. Ann Intern Med. 2007 Nov 6;147(9):603-10.

26. Cicero AFG, Gaddi A. Rice Bran and Gamma-Oryzanol in the treatment of hyperlipoproteinemias and other conditions. Phytotherapy Research. 15(4):277-289.

27. Porter GA, Palade GE, Milici AJ. Differential binding of the lectins Griffonia simplicifolia I and Lycopersicon esculentum to microvascular endothelium: organ-specific localization and partial glycoprotein characterization. Eur J Cell Biol 1990 Feb;51(1):85-95.

28. Lect. Biol. Biochem. Clin. Biochem. 1985;(4):3.

29. Mikkat U, Damm I, Schroder G, Schmidt K, Wirth C, Weber H, Jones L. Effect of the Lectin Wheat Germ Agglutinin (WGA) and Ulex europaeus Agglutinin (UEA-1) on the alpha-amylase secretion of rat pancreas in vitro and in vivo. Pancreas. 1998 May;16(4):529-38.

30. Horvath K, et al. Improved social and language skills after secretin administration in patients with autistic spectrum disorders. Journal of the Association for Academic Minority Physicians. 1998;9(1):9-15.

31. Boren T, Falk P, Roth KA, et al. Attachment of Helicobacter pylori to human gastric epithelium mediated by blood group antigens. Science. 1993; 262:1892-189

32. Kimura Y, Watanabe K, Okuda H. Effects of soluble sodium alginate on cholesterol excretion and glucose tolerance in rats. J Ethnopharmacol. 1996;54:47-54.

33. Criado MT, Ferreiros CM. Selective interaction of a Fucus vesiculosus lectin-like mucopolysaccharide with several Candida species. Ann Microbiol (Paris). 1983;134A:149-154.

34. Criado MT, Ferreiros CM. Toxicity of an algal mucopolysaccharide for Escherichia coli and Neisseria meningitides strains. Rev Esp. Fisiol. 1984;40:227-230.

35. Carroccio A, Guarino A, Zuin G, Verghi F, Berni Canani R, Fontana M, Bruzzese E, Montalto G, Notarbartolo A. Efficacy of oral pancreatic enzyme therapy for the treatment of fat malabsorption in HIV-infected patients. Aliment Pharmacol Ther. 2001 Oct;15(10):1619-25.

36. Kushak RI, Drapeau C, Winter HS. Pancreatic and intestinal enzyme activities in rats in response to balanced and unbalanced plant diets. Plant Foods Hum Nutr. 2002 Fall;57(3-4):245-55.

37. Omogbenigun FO, Nyachoti CM, Slominski BA. Dietary supplementation with multienzyme preparations improves nutrient utilization and growth performance in weaned pigs. J Anim Sci. 2004 Apr;82(4):1053-61.

38. Diop L, Guillou S, Durand H. Probiotic food supplement reduces stress-induced gastrointestinal symptoms in volunteers: a double-blind, placebo-controlled, randomized trial. Nutr Res. 2008 Jan;28(1):1-5.

Enhancing overall energy levels is particularly important during the holidays, which can be an exhausting time of year. Overall energy status in the body is dependent on several different physiological pathways and if any or all of these pathways are disrupted than fatigue can result. At the cellular level, the production of energy in the mitochondria is critical. Also, the adrenal glands can play a role as they respond to environmental stressors. In addition, neurotransmitters in the brain and the sympathetic nervous system response can impact short-term energy production.

Mitochondrial Function

Fatigue is increasingly common. In fact, 24 percent of patients report that fatigue is a major health problem.¹ Evidence suggests that mitochondrial dysfunction is a major cause of fatigue. Mitochondria are cellular structures responsible for the majority of energy production in the form of adenosine tri-phosphate (ATP), the chemical energy used by the cells. The mitochondria produce ATP through three main pathways: cellular respiration including glycolysis and the citric acid cycle, oxidative phosphorylation and beta-oxidation. Mitochondria are also involved in numerous other physiological functions such as calcium signaling, cellular differentiation, apoptosis (programmed cell death), regulation of the cell cycle and cell growth. The number of mitochondria varies between cell types, depending on how much energy is required. Mitochondria are also an interesting cell structure in that they have their own DNA for replication.

Normal energy production within the mitochondria results in the formation of damaging free radicals such as the reactive oxygen species (ROS) superoxide. The body has several antioxidant enzymes to combat the production of these free radicals. However, these enzymes, as well as the enzymes required for oxidative phosphorylation, decrease with age.² The ROS generated induce cellular oxidative stress and may contribute to age-related decline in mitochondrial function. Furthermore, the reduction in mitochondrial oxidative phosphorylation significantly impacts energy production, as this pathway provides the majority of ATP produced. Also, mitochondrial DNA mutations contribute to the decreased ATP production and increased levels of ROS seen with increasing age.³

Mitochondrial dysfunction from any cause results in decreased energy production, which may cause symptoms of fatigue. Research suggests that numerous diseases such as chronic fatigue syndrome (CFS) are associated with mitochondrial dysfunction.⁴ Several studies indicate that fatigue may be related to free radical-induced cellular oxidative stress causing oxidative damage to mitochondria, resulting in reduced efficiency of mitochondrial energy production.⁵ Optimizing mitochondrial function can support the body in long-term energy production. Research indicates that supplementation of mitochondrial nutrients and antioxidants in patients suffering with chronic fatigue reduces damage to mitochondrial membranes, restores mitochondrial energy production, protects cellular structures and enzymes from oxidative damage, and most importantly, decreases fatigue.⁶ A number of nutrients (all found in Mito-Boost^® Caps) are important in the mitochondrial synthesis of energy as well as decrease free radical damage.

Carnitine, and the derivative acetyl-L-carnitine, is important for ATP synthesis. Acetyl-L-carnitine is the precursor to the molecule acetyl coenzyme A, which is the primary substrate for creating high-energy molecules in the citric acid cycle. In addition, N-acetyl-carnitine assists in the transportation of long-chain fatty acids into the mitochondria for beta-oxidation, the process in which fatty acids are broken down to generate the substrate acetyl coenzyme A for the citric acid cycle. Carnitines also exhibit antioxidant properties, which provide protection from free radical damage. Studies indicate that conditions such as CFS and several cardiovascular diseases have low levels of carnitines, including serum acylcarnitine, total carnitine and free carnitine. Data also suggests that higher carnitine levels correlate with better functional capacity.^7-8 Similarly, research has shown that improvement in general fatigue in patients with CFS is associated with increasing concentrations of serum acylcarnitine to normal levels.⁹ Succinate is another citric acid cycle intermediate that has been shown to benefit patients with mitochondrial disorders.¹⁰

Antioxidant supplementation such as lipoic acid and N-acetyl-cysteine (NAC) is also important to reduce oxidative free radical damage. Lipoic acid has been shown to protect and repair age-related mitochondrial DNA damage, thus improving mitochondrial function and energy production.¹¹ In fact, research indicates that lipoic acid decreases levels of ROS, increases the levels of antioxidants and restores the activity of key mitochondrial enzymes.¹² Furthermore, research has demonstrated that lipoic acid in combination with acetyl-L-carnitine increases cellular metabolism and lowers oxidative stress better than either compound alone.¹³ NAC, the precursor to the potent antioxidant glutathione, has also been shown to protect mitochondrial proteins against damaging ROS and increases activity of mitochondrial complex proteins.^14-15 NAC supplementation can also directly improve the efficiency of mitochondrial energy production.¹⁶

Ribose, a five-carbon sugar, is an important subunit of the molecule ATP and adding it to the above supplementation regimen can result in increased energy and stamina. The availability of ribose can impact the rate in which ATP is synthesized. D-ribose supplementation accelerates ATP synthesis by up to 4.3-fold in muscles¹⁷ and can decrease free radical formation.¹⁸ Clinical studies indicate that supplementation of D-ribose in patients with CFS and/or fibromyalgia resulted in 66 percent of patients reporting significant improvement, with an average increase in energy of 45 percent, and an average improvement in overall well-being of 30 percent. The subjects also reported significant improvement in energy, pain intensity, sleep, mental clarity and well-being.¹⁹

The Adrenal Glands

Also important for energy and stamina, the adrenal glands play a significant role in mediating the stress response. Chronic stress is increasingly common and often presents as fatigue. There are two distinct areas in the adrenal gland: the adrenal medulla, which is responsible for secreting epinephrine (adrenaline) and norepinephrine (noradrenaline); and the adrenal cortex, which secretes steroid hormones including cortisol. The stress response activates both the hypothalamus-pituitary-adrenal (HPA) axis as well as the sympathetic nervous system-adrenal response. Perceived stress causes an increase in cortisol release, which correlates to symptoms of fatigue and anxiety.²⁰ Botanicals known as adaptogens are often used to improve the physiological resistance to stressors and balance adrenal hormone levels, thereby improving long-term energy levels and stamina.

Panax Ginseng (Korean ginseng) and Eleutherococcus senticosus, which are found in Ginseng Plus along with Rhodiola, have been traditionally used as adaptogenic herbs to modulate stress, fatigue and immune function. Research indicates that Panax ginseng directly influence the HPA axis.²¹ Evidence suggests that Panax ginseng also exhibits antioxidant and anti-inflammatory activity.²² Studies with Eleutherococcus demonstrate that this herb can improve maximal working capacity by improving oxygen metabolism reflected by an increase in maximal oxygen uptake.²³ Oxygen is a required substrate for the oxidative phosphorylation pathway for ATP synthesis in the mitochondria. In addition, animal models indicate that Eleutherococcus inhibits stress-induced cortisol increase and improves overall endurance.²⁴

Rhodiola rosea is considered to be one of the most bioactive adaptogenic herbs. In one study, Rhodiola was supplemented for 12 weeks in subjects with physical and cognitive deficiencies. The study showed a highly significant improvement in physical and cognitive deficiencies such as exhaustion, decreased motivation, daytime sleepiness, decreased libido, sleep disturbances and cognitive complaints including concentration deficiencies, forgetfulness, decreased memory, susceptibility to stress and irritability. Furthermore, 80 percent of the subjects reported the treatment as “good” or “very good.”²⁵

Other Energy Boosters

Additional nutrients have been shown to impact energy levels. Methylcobalamin is the active, functional form of vitamin B12, which is important for nerve and blood cells. One study found that administration of vitamin B12 (methylcobalamin) to subjects complaining of tiredness or fatigue resulted in reported improvement in the subject’s general well-being.²⁶ Another study showed that methylcobalamin supplementation improved plasma vitamin B12 levels as well as subjective reports of improved sleep quality, concentration, and feeling refreshed, while decreasing overall sleep duration.²⁷

Short-Term Energy Support

In addition to optimizing long-term improvements in energy production, short-term support is also helpful, especially around the holidays. Many energy drinks cause a significant drop in energy once the effect of the sugar and caffeine has worn off. However, L-phenylalanine and nutrients such as pyridoxine (vitamin B6), found in Optimum Energy^™, provides sustained energy support without the “crash.” L-phenylalanine is an essential amino acid that is metabolized into the amino acid tyrosine. Tyrosine is the precursor for the synthesis of norepinephrine, epinephrine and dopamine.

Norepinephrine is released into the blood from the adrenal medulla as a hormone and is released from noradrenergic neurons where it acts as a neurotransmitter in the central nervous system and sympathetic nervous system. Similarly, epinephrine acts as both a hormone secreted from the adrenal glands and as a neutrotransmitter in the brain. Both epinephrine and norepinephrine play a central role in the short-term stress reaction of the sympathetic nervous system, increasing the supply of oxygen and glucose to the brain and muscles.

Pyridoxine, or vitamin B6, is also important for short-term energy production. Supplementation with pyridoxine in pyridoxine-deficient animals normalized neurotransmitter levels including gamma-aminobutyric acid (GABA), serotonin, epinephrine and norepinephrine levels.²⁸

Conclusion

There are several mechanisms in which energy production can be optimized. Addressing mitochondrial and adrenal function with Mito-Boost, D-Ribose, Ginseng Plus and sublingual vitamin B12 improves long-term energy and may help alleviate fatigue. Short-term support (in the form of Optimum Energy), especially around the holidays when we need extra vitality, optimizes neurotransmitters and sympathetic nervous system hormones.

References

1. Kroenke K, Wood DR, Mangelsdorff AD, et al. Chronic fatigue in primary care. Prevalence, patient characteristics, and outcome. JAMA. 1988 Aug 19;260(7):929-34.

2. Cortopassi GA, Wong A. Mitochondria in organismal aging and degeneration. Biochim Biophys Acta. 1999 Feb 9;1410(2):183-93.

3. Wei YH, Lee HC. Oxidative stress, mitochondrial DNA mutation, and impairment of antioxidant enzymes in aging. Exp Biol Med (Maywood). 2002 Oct;227(9):671-82.

4. Pieczenik SR, Neustadt J. Mitochondrial dysfunction and molecular pathways of disease. Exp Mol Pathol. 2007 Aug;83(1):84-92.

5. Nicolson GL. Metabolic syndrome and mitochondrial function: molecular replacement and antioxidant supplements to prevent membrane peroxidation and restore mitochondrial function. J Cell Biochem. 2007 Apr 15;100(6):1352-69.

6. Nicolson GL, Conklin KA. Reversing mitochondrial dysfunction, fatigue and the adverse effects of chemotherapy of metastatic disease by molecular replacement therapy. Clin Exp Metastasis. 2008;25(2):161-9.

7. Plioplys AV, Plioplys S. Serum levels of carnitine in chronic fatigue syndrome: clinical correlates. Neuropsychobiology. 1995;32(3):132-8.

8. Carvajal K, Moreno-Sanchez R. Heart metabolic disturbances in cardiovascular diseases. Arch Med Res. 2003;34:89-99.

9. Kuratsune H, Yamaguti K, Takahashi M, et al. Acylcarnitine deficiency in chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S62-7.

10. Shoffner JM, Lott MT, Voljavec AS, et al. Spontaneous Kearns-Sayre/chronic external ophthalmoplegia plus syndrome associated with a mitochondrial DNA deletion: a slip-replication model and metabolic therapy. Proc Natl Acad Sci USA. 1989 Oct;86(20):7952-6.

11. McCarty MF, Barroso-Aranda J, Contreras F. The “rejuvenatory” impact of lipoic acid on mitochondrial function in aging rats may reflect induction and activation of PPAR-gamma coactivator-1alpha. Med Hypotheses. 2009 Jan;72(1):29-33.

12. Hagen TM, Ingersoll RT, Lykkesfeldt J, et al. (R)-alpha-lipoic acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate. FASEB J. 1999 Feb;13(2):411-8.

13. Liu J. The effects and mechanisms of mitochondrial nutrient alpha-lipoic acid on improving age-associated mitochondrial and cognitive dysfunction: an overview. Neurochem Res. 2008 Jan;33(1):194-203.

14. Banaclocha MM. Therapeutic potential of N-acetylcysteine in age-related mitochondrial neurodegenerative diseases. Med Hypotheses. 2001 Apr;56(4):472-7.

15. Nicoletti VG, Marino VM, Cuppari C, et al. Effect of antioxidant diets on mitochondrial gene expression in rat brain during aging. Neurochem Res. 2005 Jun-Jul;30(6-7):737-52.

16. Cocco T, Sgobbo P, Clemente M, et al. Tissue-specific changes of mitochondrial functions in aged rats: effect of a long-term dietary treatment with N-acetylcysteine. Free Radic Biol Med. 2005 Mar 15;38(6):796-805.

17. Hellsten Y, Skadhauge L, Bangsbo J. Effect of Ribose Supplementation on Resynthesis of Adenine Nucleotides after Intermittent Training in Humans. AM J Physiol, Regul Intergr Comp Physiol. 2004;286:R182-R188.

18. Seifert JG, Subhudi A, Fu M-X, et al. The Effects of Ribose Ingestion on Indicies or Free Radical Production During Hypoxic Exercise. Free Rad Biol Med. 2002;33(Suppl 1):S269.

19. Teitelbaum JE, Johnson C, St Cyr J. The use of D-ribose in chronic fatigue syndrome and fibromyalgia: a pilot study. J Altern Complement Med. 2006;12(9):857-62.

20. Izawa S, Sugaya N, Ogawa N, et al. Episodic stress associated with writing a graduation thesis and free cortisol secretion after awakening. Int J Psychophysiol.2007 May;64(2):141-5.

21. Hiai S, Yokoyama H, Oura H, et al. Stimulation of pituitary-adrenocortical system by ginseng saponin. Endocrinol Jpn. 1979 Dec;26(6):661-5.

22. Radad K, Gille G, Liu L, et al. Use of ginseng in medicine with emphasis on neurodegenerative disorders. J Pharmacol Sci. 2006 Mar;100(3):175-86.

23. Asano K, Takahashi T, Miyashita M, et al. Effect of Eleutheroccocus senticosus Extract on Human Physical Working Capacity. Planta Med. 1986 Jun;52(3):175-7.

24. Kimura Y, Sumiyoshi M. Effects of various Eleutherococcus senticosus cortex on swimming time, natural killer activity and corticosterone level in forced swimming stressed mice. J Ethnopharmacol. 2004 Dec;95(2-3):447-53.

25. Fintelmann V, Gruenwald J. Efficacy and tolerability of a Rhodiola rosea extract in adults with physical and cognitive deficiencies. Adv Ther. 2007 Jul-Aug;24(4):929-39.

26. Ellis FR, Nasser S. A pilot study of vitamin B12 in the treatment of tiredness. Br J Nutr. 1973;30:277-83.

27. Mayer G, Kröger M, Meier-Ewert K. Effects of vitamin B12 on performance and circadian rhythm in normal subjects. Neuropsychopharmacology. 1996 Nov;15(5):456-64.

28. Paulose CS, Dakshinamurti K, Packer S, et al. Sympathetic stimulation and hypertension in the pyridoxine-deficient adult rat. Hypertension. 1988 Apr;11(4):387-91.

As we enter into the holiday season, it is important to remember that the excessive stress occurring at this time of year and winter weather can impact overall skin health. During the holiday season our skin is vulnerable to numerous factors including stress, lack of sleep, eating a less-than-optimal diet, cold weather in many parts of the country and the damaging effects of heaters.

Lack of sleep commonly becomes apparent with dark circles under the eyes. Dark circles under the eyes are due to the appearance of blood vessels through the very thin skin under the eye. Aging, and the related thinning of the skin and loss of the protein collagen, results in even more apparent dark circles. Lack of sleep can also cause a decrease in the skin’s ability to heal and an increase in pro-inflammatory cellular chemicals that affect the skin.¹

In addition, low humidity during the winter months can also adversely affect the skin. In fact, researchers have shown that during the winter months, the skin is more prone to irritation and trans-epidermal water loss.² Other studies have shown that winter weather induces a mild inflammatory response in exposed skin, such as on the face.³ Additionally, irritated skin that is dry or otherwise sensitive has been shown to worsen during low temperatures and low humidity as seen during the winter months.⁴

The holiday season is notorious for inducing chronic stress, often resulting in disrupted cortisol levels. Cortisol, which is the primary hormone secreted during the stress response, has been shown to alter the physiology of the skin resulting in thinning of the skin and impaired wound healing.⁵

In addition to all of these factors, eating holiday favorites including foods high in sugar can also adversely impact skin health. Research indicates that young human skin cells age rapidly when exposed to glucose (blood sugar).⁶ Increased levels of blood glucose induce a process known as glycosylation. Sugars can irreversibly attach to biological proteins resulting in the formation of advanced glycation end products (AGEs). AGEs accumulate and can react with molecules creating cross-linkages, causing them to become less elastic and less digestible by enzymes for degradation. Eating foods high in sugar has been shown to increase AGE formation as well as increase pro-inflammatory markers.⁷ In the skin, the structural protein collagen is highly susceptible to glycosylation due to a slow turnover rate.⁸ Glycosylated collagen is less elastic resulting in wrinkles, dryness and sagging skin. Fibroblasts, the connective tissue cells that synthesize collagen, are also susceptible to reactions with AGEs as research indicates that AGEs can distort fibroblast structure and function.⁹ Furthermore, studies have shown that AGEs can decrease the synthesis of hyaluronic acid, a natural moisturizing agent in the skin.¹⁰

Hyaluronic acid is a naturally occurring substance within the body that belongs to the class of compounds known as glycosaminoglycans (GAGs). Hyaluronic acid is found in several places in the body such as the eyes, joint fluid and cartilage, and is a major component of skin. In the skin, hyaluronic acid has several important physiological functions.

Hyaluronic acid in the skin is important for wound healing. External stress, such as ultraviolet (UV) light exposure, can decrease the production and increase the breakdown of hyaluronic acid in the deeper layer and metabolically active layer of skin, the dermis.¹¹ Hyaluronic acid also attracts water into the dermis layer of the skin, which hydrates collagen and promotes water retention. Hyaluronic acid has the amazing ability to hold up to 1,000 times its own weight in water. This function allows for skin elasticity, which prevents wrinkle formation. Young skin contains abundant levels of hyaluronic acid, allowing for the smooth and elastic appearance. As we age, hyaluronic become more tissue-associated and levels decrease in the upper layer of skin, the epidermis, and accumulate in deeper layers of skin. This results in the apparent dryness associated with aged skin.¹² Also, hyaluronic acid levels decline with aging, causing a decrease in the ability of the skin to retain water.¹² This results in drier, thinner and looser skin that is less able to heal and restore itself.

Hyaluronic acid can be applied topically to the skin by using such products as Hyaluronic Acid Serum and Facelift Serum to increase levels of hyaluronic acid in the dermis and to attract a water layer on top of the skin surface protecting the skin against water loss. This provides elasticity to help prevent wrinkles, as well as hydration to reduce dryness and thinning of the skin. Additionally, hyaluronic acid can be used under the eye area to reduce the appearance of under eye circles and fine lines by improving microcirculation and collagen integrity. For additional skin support, hyaluronic acid can be applied topically to tighten loose skin and decrease oxidative damage from sources such as UV light, smoke exposure or pollution.

References

1. Altemus M, Rao B, Dhabhar FS, et al. Stress-induced changes in skin barrier function in healthy women. J Invest Dermatol. 2001 Aug;117(2):309-17.

2. Loffler H, Happle R. Influence of climatic conditions on the irritant patch test with sodium lauryl sulphate. Acta Derm Venereol. 2003;83(5):338-41.

3. Kikuchi K, Kobayashi H, Hirao T, et al. Improvement of mild inflammatory changes of the facial skin induced by winter environment with daily applications of a moisturizing cream. A half-side test of biophysical skin parameters, cytokine expression pattern and the formation of cornified envelope. Dermatology. 2003;207(3):269-75.

4. Uter W, Gefeller O, Schwanitz HJ. An epidemiological study of the influence of season (cold and dry air) on the occurrence of irritant skin changes of the hands. Br J Dermatol. 1998 Feb;138(2):266-72.

5. Zervolea I, Pratsinis H, Tsagarakis S, et al. The impact of chronic in vivo glucocorticoid excess on the functional characteristics of human skin fibroblasts obtained from patients with endogenous Cushing’s syndrome. Eur J Endocrinol. 2005 Jun;152(6):895-902.

6. Berge U, Behrens J, Rattan SI. Sugar-induced premature aging and altered differentiation in human epidermal keratinocytes. Ann N Y Acad Sci. 2007 Apr;1100:524-9.

7. Ahmed N, Babaei-Jadidi R, Howell SK, et al. Glycated and oxidized protein degradation products are indicators of fasting and postprandial hyperglycemia in diabetes. Diabetes Care. 2005 Oct;28(10):2465-71.

8. Thirunavukkarasu V, Nandhini AT, Anuradha CV. Fructose diet-induced skin collagen abnormalities are prevented by lipoic acid. Exp Diabesity Res. 2004 Oct-Dec;5(4):237-244.

9. Lohwasser C, Neureiter D, Weigle B, et al. The receptor for advanced glycation end products is highly expressed in the skin and upregulated by advanced glycation end products and tumor necrosis factor-alpha. J Invest Dermatol. 2006 Feb;126(2):291-299.

10. Okano Y, Masaki H, Sakurai H. Dysfunction of dermal fibroblasts induced by advanced glycation end-products (AGEs) and the contribution of a nonspecific interaction with cell membrane and AGEs. J Dermatol Sci. 2002 Sep;29(3):171-180.

11. Averbeck M, Gebhardt CA, Voigt S, et al. Differential regulation of hyaluronan metabolism in the epidermal and dermal compartments of human skin by UVB irradiation. J Invest Dermatol. 2007 Mar;127(3):687-97.

12. Meyer LJ, Stern R. Age-dependent changes of hyaluronan in human skin. J Invest Dermatol. 1994;102:385-389.

Most folks do not think of fruit as a food for dogs and yet coyotes will steal apples from trees and eat them. Could it be they know more than we do? I have used Xango (mangosteen) juice mixed in the food for several dogs that seemed to be a little tired and lethargic, and had a very good response. In addition, I have used Noni (noni fruit) on dogs to a similar effect. Cats also benefit by consuming fruits.

That’s why I’m excited about the Liquid Superfruit Antioxidant that VRP is producing. LSA is a blend of 14 health-promoting fruits, including some exotic varieties.

Let’s start with mangosteen, which is a fruit that I have used in pets in the past as a fruit drink. This fruit comes from Southeast Asia and is so fragile it is almost impossible to ship like an orange or kiwi. It has a number of xanthones, which are great antioxidants. They are excellent free radical oxygen scavengers, and there has been extensive research done on their effects. The entire fruit including the rind is used, as the thick purple rind is loaded with the xanthones.

The next superfruit is Açai. The ORAC value (a laboratory measure of antioxidant ability) is one of the highest of the superfruits.

The fruit has a small amount of flesh around a large seed and it takes a large amount of seeds to yield the extract used.

There are some great antioxidant reports from people who use the product. I do not have any direct information towards the use on pets, but I expect it to be very helpful.

Gogi, known as wolfberry, is another superfruit and it comes out of the high mountains of Southeast Asia and southeast Europe. The primary commercial access is from Tibet or the Ningxia area of China.

The next superfruit is Noni, which can be considered the nexus of the superfruit industry. It contains a number of compounds that appear to help with the well being of warm-blooded animals.

Next we move into fruits that we may consider to be everyday fruits that are usually on the shelf or in the freezer, but yet are still not eaten by dogs and cats in sufficient quantities to promote overall health. Blueberries have been shown to be very helpful in cognition. If blueberries were not so common, they might be considered a superfruit along with the ones above. They contain anthocyanins, proanthocyandins, resveratrol, flavonols and tannins.

Sour cherries have some excellent antioxidant properties and are one of a few known sources of melatonin. Pomegranate has been the latest fruit de jour. This contains a different antioxidant called punicalagins, which appear to have functions in the immune, cardiovascular and prostate areas.

Grape skin, seed and fruit, have resveratrol and proanthocyanidins. Resveratrol seems to have an ability to increase lifespan and the proanthocyanidins are excellent antioxidants. As you know, grapes are toxic to dogs but the resveratrol and proanthocyanidins are very helpful and the extract does not appear to have the same problems as the grapes or raisins.

Cranberry has a number of effects and has been most commonly used to help keep bacteria from sticking to the urinary bladder wall in those animals that have recurrent cystitis. Raspberries and boysenberries have excellent amounts of antioxidants and contain elegiac acid, which may help slow or prevent cancer.

The Liquid Superfruit Antioxidant mixture contains all the fruits mentioned above—some of the world’s best-known antioxidants and wellness support compounds. For the old dog or cat that seems to have lost its get up and go but has normal blood values, one half to one ounce per day may make a real difference. Seeing these effects occur with the use of mangosteen or noni makes me believe this product will be even more helpful, and I am starting some dogs on it now.

AdaptaPhase^® I is an adaptogenic formula designed to combat the damaging effects of stress on the adrenal glands. The newly reformulated AdaptaPhase I includes five of the most powerful adaptogens from around the world.

Adaptogens are natural stress-fighting agents that help support the health of the adrenal glands. Studies show that psychological stress activates the hypothalamus-pituitary-adrenal axis causing an increase in morning cortisol levels. Although this stress response is important for survival during an acute stressor, prolonged activation of the stress response may lead to adrenal exhaustion in which cortisol levels drop to insufficient levels resulting in fatigue or illness.

Adaptogenic herbs can increase low levels of adrenal hormones or decrease levels that are elevated. Additionally, these herbs provide balancing activity on many body systems that are impacted by stress, such as the immune response and blood sugar maintenance.

The following adaptogens are contained within the newly reformulated AdaptaPhase I, providing a strong foundation for adrenal health and increasing overall energy levels.

Astragalus

Astragalus is used as an important “Qi (Chi) tonifying” herb in Chinese medicine. It helps support immunity and has stamina-building properties. It is rich in polysaccharides known for their immune-modulating actions.¹

In animal studies, astragalus enhanced numerous indicators of immune function including superoxide anion production by peritoneal macrophages, potentiation of phagocytic function, increased thymus weight and proliferation of splenocytes.²

Other studies have shown that astragalus polysaccharides could increase the immune-mediated antitumor activity of interleukin-2 (IL-2), increase the immune activity of lymphocytes from normal subjects and cancer patients and enhance the natural killer cell activity in both normal subjects and subjects with systemic lupus erythematosis (SLE).³

In a number of human studies, astragalus also has demonstrated antiviral activity. In viral myocarditis patients, the botanical enhanced the activity of T cells, an indicator of immune response.⁴ Astragalus also increased the efficacy of interferon treatment in patients with chronic cervicitis associated with the human papilloma virus (HPV), herpes simplex virus type 2 and cytomegalovirus.⁵

A new rodent study also demonstrated its adaptogenic properties. Astragalus reduced chronic fatigue in rats undergoing food intake restriction and forced swimming.⁶

Withania Somnifera (Ashwagandha)

Ashwagandha, often referred to as Indian ginseng, is a botanical possessing anti-inflammatory, anti-stress, antioxidant, antitumor, immunomodulating and rejuvenating properties. It is known to favorably affect the endocrine, cardiopulmonary and central nervous systems.⁷

Animal studies have indicated that Withania somnifera can help offset the damaging effects of stress. In one study, mice were given either Withania somnifera or a control and then were forced to undergo a swimming performance test. In mice given the Withania somnifera, swimming time was doubled compared to controls.⁸Withania somnifera prevented both a weight increase of the adrenals and a reduction in ascorbic acid content in the adrenals that normally occurs in untreated animals undergoing the swimming test.⁷

Other evidence derived from animal studies shows that Withania somnifera lowers the increases in blood urea nitrogen levels and blood lactic acid that occur after stress as well as reducing adrenal hypertrophy.⁹ This adaptogenic botanical also reduced levels of the stress hormone corticosterone in rodents during a cold swimming test.⁹

Eleutherococcus Senticosus

This powerful adaptogen has been traditionally used for modulation of stress and fatigue as well as immune-stimulating action. In a single-blind, placebo-controlled crossover study, supplementation with Eleutherococcus was evaluated in regards to maximal working capacity in adolescent males. The results indicated a 23.3 percent increase in total work after Eleutherococcus supplementation.¹⁰

Animal studies measuring forced swimming time show that supplementation with Eleutherococcus helped inhibit stress-induced cortisol increase and stress-induced immune suppression and improves endurance demonstrated by increased swimming time.¹¹

Schisandra

Schisandra is another adaptogenic traditional Chinese botanical. Evidence suggests that adaptogens such as Schisandra support the stress response both by affecting the sympathetic-adrenal response with short-term administration as well as supporting the hypothalamic-pituitary-adrenal axis with longer-term administration.^12-13

Studies using animal models confirm that Schisandra can reduce elevated serum corticosterone levels.¹⁴

Aralia Manchurica
(Manchurian Thorn Tree)

This botanical has historically been used in Russia as an adaptogen for fatigue, weakness, headaches, depression, immune support, and stress-overload. One study showed a 90 percent success rate using this herb in individuals with stress overload and weakness.¹⁵

References

1. No authors listed. Astragalus Membranaceus. Monograph. Alternative Medicine Review. 2003;8(1):72-77.

2. Mills S, Bone K. Principles and Practice of Phytotherapy. Edinburgh, Scotland. Churchill, Livingstone: 2000:273-79.

3. Zhao XZ. Effects of Astragalus membranaceus and Tripterygium hypoglancum on natural killer cell activity of peripheral blood mononuclear cells in systemic lupus erythematous. Chung Kuo Chung Hsi I Chieh Ho Tsa Chih. 1992;12:679-671.

4. Huang ZQ, Qin NP, Ye W. Effect of Astragalus membranaceus on T-lymphocyte subsets in patients with viral myocarditis. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1995;15:328-330.

5. Qian ZW, Mao SJ, Cai XC, et al. Viral Etiology of Chronic Cervicitis And Its Therapeutic Response to a Recombinant Interferon. Chin Med J (Engl) 1990;103:647-651.

6. Kuo YH, Tsai WJ, Loke SH, Wu TS, Chiou WF. Astragalus membranaceus flavonoids (AMF) ameliorate chronic fatigue syndrome induced by food intake restriction plus forced swimming. Journal of Ethnopharmacology. 2009;122:28-34.

7. Mishra LC, Singh BB, Dagenais S. Scientific Basis for the Therapeutic Use of Withania Somnifera (Ashwagandha): A Review. Alternative Medicine Review. 2000;5(4):334-346.

8. Singh N, Nath R, Lata A, et al. Withania Somnifera (Ashwagandha), a Rejuvenating Herbal Drug Which Enhances Survival During Stress (An Adaptogen). Int J Crude Drug Res. 1982;20:29-35.

9. Dadkar VN, Ranadive NU, Dhar HL. Evaluation of Antistress (Adaptogen) Activity of Withania Somnifera (Ashwagandha). Ind J Clin Biochem. 1987;2:101-108.

10. Kimura Y, Sumiyoshi M. Effects of various Eleutherococcus senticosus cortex on swimming time, natural killer activity and corticosterone level in forced swimming stressed mice. J Ethnopharmacol. 2004 Dec;95(2-3):447-53.

11. Upton R, ed. Schisandra Berry: Analytical, quality control, and therapeutic monograph. Santa Cruz, CA: American Herbal Pharmacopoeia 1999;1-25.

12. Panossian A, Wagner H. Stimulating effect of adaptogens: an overview with particular reference to their efficacy following single dose administration. Phytother Res. 2005 Oct;19(10):819-38.

13. Lee S, Kim DH, Jung JW, et al. Schizandra chinensis and Scutellaria baicalensis counter stress behaviors in mice. Phytother Res. 2007 Dec;21(12):1187-92.

14. Chiu PY, Leung HY, Ko KM. Schisandrin B Enhances Renal Mitochondrial Antioxidant Status, Functional and Structural Integrity, and Protects against Gentamicin-Induced Nephrotoxicity in Rats. Biol Pharm Bull. 2008 Apr;31(4):602-5.

15. Martinez B, Staba EJ. The physiological effects of Aralia, Panax and Eleutherococcus on exercised rats. Jpn J Pharmacol. 1984 Jun;35(2):79-85.

Anyone who has experienced a painful injury is all too familiar with its consequences, especially the accompanying unpleasant sensation and loss of mobility. Pain is not a disease, but a symptom of an underlying imbalance. It is defined by the International Association for the Study of Pain as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. Simply stated, pain is a warning mechanism.

Pain is the most frequent reason for physician consultations in the United States, and results in half of all Americans to seek medical care annually. Chronic pain is the third most common healthcare problem and impacts productivity, mobility, and quality of life. More than one-third of the estimated 75 to 85 million persons in the United States who report chronic pain are partially or totally disabled.1

Arthritis, a common cause of chronic pain and activity limitation, also is characterized by localized pain and swelling. Approximately 46.9 million adults in the United Stated have been diagnosed with arthritis.2 The prevalence of arthritis is increasing, and it is estimated that by the year 2030, 67 million adult Americans will be afflicted with this condition.3

The most common chronic pain condition is back and neck pain. According to the National Pain Foundation, approximately 85 percent of Americans will experience back pain by age 50, and more than 26 million Americans between the ages of 20 and 64 experience frequent back pain.4

People differ remarkably in their ability to tolerate pain. Tolerance levels can vary depending on several factors including mood, personality, and circumstance. Despite its subjective nature, most pain is associated with tissue damage and has a physiological basis.

Pain is categorized as acute or chronic. Acute pain begins suddenly and is short in duration, while chronic pain can last for weeks to years. Chronic pain typically lasts for at least one month longer than expected based on the illness or injury, recurs on and off for months or years, or is associated with a chronic disease or injury that does not heal. Chronic pain may result in depression, loss of interest in activities, sleep problems, decreased energy, decreased appetite, weight loss, and decreased sex drive. Chronic pain can make the nervous system more sensitive to pain by repeatedly stimulating the nerve fibers and cells that detect, send, and receive pain signals. Repeated stimulation can cause changes in the structure of nerve fibers or make them more active resulting in increased pain transmission to the spinal cord and brain.5

The Physiology of Pain

Pain receptors are located almost everywhere in the body, especially the skin, surfaces of the joints, the lining around the bone, and walls of the arteries. Pain from various sources stimulates these receptors, and this stimulus is transferred via specialized nerves to the spinal cord and up to the brain. The brain then processes the pain stimulus and sends an impulse down the spinal cord that commands the body to respond.

Pain receptors (nociceptors) are nerve fibers with endings that can be excited by three types of stimuli: mechanical, thermal, and chemical. Mechanical receptors respond to pressure or stretching. Thermal receptors respond to extreme heat or cold. Chemical receptors react to various stimuli from both internal and external sources including chemical mediators from trauma or inflammation. For example, specific prostaglandins are pro-inflammatory mediators that are locally released with painful stimuli and inflammation and cause increased sensitivity of the pain receptors. Other chemical substances produced by the body that excite pain receptors include bradykinin, serotonin, and histamine. Thus, controlling inflammatory mediators can directly impact pain perception.

Pain signals can also be selectively inhibited in the spinal cord. This analgesic (pain-relieving) response is controlled by neurochemicals called endorphins, which are opioid peptides such as enkephalins that are produced by the body. These substances block reception of stimuli by binding to receptors. Enhancing this natural pain-reducing pathway also can modulate the perception of pain.

Natural Support for Pain

Pain is clearly one of the most common health problems of our time. However, both clinical practice and research indicate that pain is something that can be conquered. One of the most effective natural approaches involves the amino acid DL-phenylalanine, the botanicals turmeric and boswellia serrata, and the proteolytic enzyme nattokinase. Unlike other substances such as glucosamine sulfate, which acts to correct tissue damage after it has occurred, these synergistic substances work specifically to inhibit pain.

DL-Phenylalanine

L-phenylalanine is an essential amino acid metabolized into tyrosine, which is the precursor used for the synthesis of the neurotransmitters norepinephrine, epinephrine, and dopamine. DL-Phenylalanine is a 50-50 mixture of L-phenylalanine and its mirror image molecule D- phenylalanine. DL- Phenylalanine is among a number of compounds that have been shown to inhibit the break down of enkephalins, which are the body’s natural opioid pain reducers.
DL-phenylalanine has been used successfully for the management of chronic pain in humans. DL-phenylalanine also exhibits anti-inflammatory properties. It is proposed that the enkephalinase inhibitors may be effective in a number of human “endorphin deficiency diseases” such as depression and arthritis. DL-phenylalanine may alleviate other conditions associated with decreased endorphin levels such as opiate withdrawal symptoms as well.7 Animal models indicate that DL-phenylalanine supplementation can increase the pain threshold. It is hypothesized that this analgesia is induced by phenylalanine blocking enkephalin degradation by the enzyme carboxypeptidase A.

Preliminary studies of chronic pain patients have shown a response rate to DL-phenylalanine from 32 percent to 75 percent.8 Analysis suggests that it may be mediated in part by up-regulation of the endogenous analgesia system (EAS). Since enkephalins are key neurotransmitters in the EAS, it is reasonable to suggest that promoting enkephalin activity by DL-phenylalanine should potentiate EAS-mediated analgesia.

Turmeric (Curcuma longa)

Turmeric (Curcuma longa) is used for numerous inflammatory conditions as it has anti-inflammatory and antioxidant activity. The primary constituent is curcumin, which is believed to exert these anti-inflammatory properties. Preliminary studies have shown turmeric may be supportive in several conditions such as inflammatory bowel disease, rheumatoid arthritis, inflammatory eye diseases, chronic pancreatitis, psoriasis, hyperlipidemia, and cancers.9

Curcumin has been shown to inhibit important enzymes that mediate inflammatory processes in the body. These enzymes are cyclooxygenase (COX), lipoxygenase (LOX), and inducible nitric oxide synthase (iNOS).10 Improper up-regulation of COX-2 and iNOS has been associated with the pathology of inflammatory disorders as well as certain types of cancer. A number of studies have been conducted that support curcumin-mediated regulation of the COX and LOX pathways at both the cellular and molecular level.11

In one study, the anti-inflammatory properties of turmeric were evaluated using animal models of rheumatoid arthritis. The results showed that turmeric profoundly inhibited joint inflammation and joint destruction in a dose-dependent manner. Turmeric prevented local activation of NFkB, which is involved in regulation of expression of the pro-inflammatory enzymes COX-2 and iNOS. Additionally, inflammatory cell influx, joint levels of pro-inflammatory prostaglandin E2, and local osteoclast (cells that resorb bone) formation were inhibited by turmeric extract treatment.12

Boswellia serrata

Boswellia serrata, also known as Indian frankincense, is widely used as a traditional herb in Ayurvedic medicine for treating inflammatory disease and has reported anti-inflammatory and analgesic activity. The resin, or gum, from the plant contains boswellic acids, which produce much of this plant’s anti-inflammatory activity. It is believed that the mechanism of action for the anti-inflammatory activity of the boswellic acids is the ability to inhibit the synthesis of pro-inflammatory leukotrienes and the enzyme 5-lipoxygenase (5-LOX). Several clinical trials have attributed beneficial effects of this herb in treating chronic inflammatory diseases such as rheumatoid arthritis, chronic colitis, ulcerative colitis, Crohn’s disease, asthma, and tumor-associated brain edema.13

In a randomized, double-blind, placebo-controlled crossover study in 30 patients with osteoarthritis of the knee, Boswellia serrata extract or placebo was given for 8 weeks. All of the patients receiving Boswellia supplementation reported a decrease in knee pain and frequency of swelling, and an increase in knee flexion and walking distance.14

Nattokinase

Nattokinase is a proteolytic (protein-dissolving) enzyme derived from a Japanese food known as natto, a preparation of soybeans that has undergone fermentation with a bacterium known as Bacillus subtilis natto.15 Proteolytic enzymes have analgesic effects in addition to their well-recognized anti-inflammatory and anti-edemic properties, indicating they may have a role to play in pain management. Enzyme-derived analgesia is based on inhibition of the inflammatory cascade as well as exerting a direct influence on nociceptors.16 Enzymes increase speed of healing and pain relief, and decrease inflammation.

Another mechanism by which nattokinase may help control pain is through its actions as a fibrinolytic enzyme, which means it breaks down fibrin deposits by inactivating plasminogen activator inhibitor 1 (PAI-1).17 Studies show that it has fibrinolytic activity 4-times more potent than plasmin, the body’s natural fibrinolytic enzyme.18 The fibrinolytic system is closely linked to control of inflammation, and plays a role in disease states associated with inflammation.

In animal studies, nattokinase can reduce markedly the thickening of blood vessel walls that normally occurs following an injury to the blood vessel lining (endothelium). In addition, nattokinase leads to dissolution of clots that build inside vessel walls as responses to injuries.19 Enzyme therapy is used to digest the fibrin and reverse the inflammation, which is the likely mechanism by which nattokinase may help to reduce pain.

Conclusion

Controlling pain is a challenge for many individuals. It is a major symptom in numerous medical conditions, and can significantly interfere with a person’s quality of life and general functioning. Natural substances that inhibit inflammation and work directly on the sensitivity of the nervous system may improve the body’s natural pain-reducing mechanisms. Therefore, consuming a synergistic blend of DL-phenylalanine, turmeric, boswellia serrata, and nattokinase, (all found in Back in Action™) which work directly on pain and inflammation, may help individuals regain mobility.

References

1. National Pain Education Council. Available at: http://www.npecweb.org/aboutnpec.asp?id=22&selMenu=2,8. Accessed on: 05-12-08.

2. Center for Disease Control and Prevention. Fastats. Available at: http://www.cdc.gov/nchs/fastats/arthrits.htm. Accessed on 2-13-08.

3. Arthritis Foundation. News from the Arthritis Foundation. Available at: http://www.arthritis.org/media/newsroom/media-kits/Arthritis_Prevalence.pdf. Accessed on 2-13-08.

4. National Pain Foundation. Common Causes of Back and Neck Pain and Your Treatment Options. Available at: http://www.nationalpainfoundation.org/MyTreatment/articles/BackAndNeck_Part_1.asp. Accessed on: 05-12-08.

5. Merck and Co., Inc. Introduction: Pain: Merck Manual Home Addition. Available at: http://www.merck.com/mmhe/sec06/ch078/ch078a.html. Accessed on: 05-12-08.

6. Ehrenpreis S. Pharmacology of enkephalinase inhibitors: animal and human studies. Acupunct Electrother Res. 1985;10(3):203-208.

7. Ehrenpreis S. D-phenylalanine and other enkephalinase inhibitors as pharmacological agents: implications for some important therapeutic application. Acupunct Electrother Res. 1982;7(2-3):157-172.

8. Walsh NE, Ramamurthy S, Schoenfeld L, et al. Analgesic effectiveness of D-phenylalanine in chronic pain patients. Arch Phys Med Rehabil. 1986 Jul;67(7):436-439.

9. Hsu CH, Cheng AL. Clinical studies with curcumin. Adv Exp Med Biol. 2007;595:471-480.

10. Menon VP, Sudheer AR. Antioxidant and anti-inflammatory properties of curcumin. Adv Exp Med Biol. 2007;595:105-125.

11. Rao CV. Regulation of COX and LOX by curcumin. Adv Exp Med Biol. 2007;595:213-26.

12. Funk JL, Frye JB, Oyarzo JN, et al. Efficacy and mechanism of action of turmeric supplements in the treatment of experimental arthritis. Arthritis Rheum. 2006 Nov;54(11):3452-3464.

13. Ammon HP. Boswellic acids (components of frankincense) as the active principle in treatment of chronic inflammatory diseases [in German]. Wien Med Wochenschr. 2002;152(15–16):373–378.

14. Kimmatkar N, Thawani V, Hingorani L, et al. Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee--a randomized double blind placebo controlled trial. Phytomedicine. 2003 Jan;10(1):3-7.

15. Sumi H, Hamada H, Tsushima H, et al. A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese natto; a typical and popular soybean food in the Japanese diet. Experientia. 1987;43:1110–1111. 56–67.

16. Klein G, Kullich W. Reducing pain by oral enzyme therapy in rheumatic diseases. Wien Med Wochenschr. 1999;149(21–22):577–580.

17. Urano T, Ihara H, Umemura K, et al. The profibrinolytic enzyme subtilisin NAT purified from Bacillus subtilis Cleaves and inactivates plasminogen activator inhibitor type 1. J Biol Chem. 2001 Jul 6;276(27):24690-24696.

18. Fujita M, Hong K, Ito Y, et al. Thrombolytic effect of nattokinase on a chemically induced thrombosis model in rat. Biol Pharm Bull. 1995 Oct;18(10):1387-1391.

19. Suzuki Y, Kondo K, Ichise H, et al. Dietary supplementation with fermented soybeans suppresses intimal thickening. Nutrition. 2003 Mar;19(3):261-264.