• The President’s Desk  — Genetics of Nutrition

• Metabolic Syndrome  — Novel Botanical Inhibits This Modern Day Threat to Heart Health

• Holiday Immune Support  — Sugar + Stress = Vulnerability to Colds and Flu

• Liver Health  — Protection from Toxins, Alcohol and Damaging Compounds Released During Weight Loss

• Vitamin D3  — Novel Delivery System Combines Essential Nutrient with MCT Oil

• Pet Corner  — The High Price of Cheap Dog Food

• Homocysteine  — The Amino Acid with Life or Death Implications

• Nutrition Review  — Latest Research on Depression, Kidney Stones, Joint Pain, Immunity and More

• Gingivitis/Periodontal Disease
• PRESSURE-fX™ and PHF
• Arrhythmia and Chelation
• Diverticulosis
• Anti-Aging Program
• Adrenal Health
• Scleroderma, Osteopenia, Blood Sugar
• Acid Reflux, Hernia
• Grave's Disease
• ADHD
• Patches on Arms
• Menopausal Symptoms

Our chief science officer Jeffrey Reinhardt, MSc recently attended the Molecular Genetics of Aging Meeting at Cold Spring Harbor Laboratory on Long Island, New York. This meeting attracted over 250 scientists and research clinicians from around the world who discussed various aspects of the genetics of nutrition. Jeffrey was the only scientist from a natural products company there. As he shared with us what he had learned there, he affirmed our interest in an exciting subject we have researched for two years.

It’s becoming more apparent that nutrients can up regulate and down regulate genes. This is important because knowing our genetic individualities is the first step toward personalized nutritional support. The genetics of nutrition will allow us to validate which nutrients each individual will find the most effective and dramatically increase the beneficial results already obtained by nutritional supplementation. Genetic knowledge can help us provide a personalized nutritional assessment and also assist with product development and ingredient selection.

Certain companies already claim to offer genetic testing. During our investigation, we have concluded that the early entrants simply do not meet our scientific standards. Consequently, we have been and are approaching this very carefully, just as we do with all our products. However, based on what Jeffrey learned at the conference, we believe the advancements are nearing the point where our company can get behind quality work.

We’re cognizant of the privacy issues surrounding this topic. Therefore, prior to proceeding, we will be very rigorous and exercise substantial due diligence as we fully analyze all aspects of genetic testing. The test results need to be communicated accurately, clearly and confidentially to each person or their healthcare provider, in order for their personal health status and longevity potential to be either self-interpreted and/or discussed with a qualified, nutritionally oriented, medical geneticist.

We will keep you informed about our progress in researching one of the most important health discoveries of our time.

Metabolic syndrome is something individuals often read about but aren’t sure how it is applicable to their own lives. However, metabolic syndrome is a very real threat to anyone who succumbs to the pressures of job stress, the temptation of refined carbs and sugar, and the reluctance to exercise when busy schedules demand too much time. In essence, the metabolic syndrome can “sneak up on” people as they go about tending to the demands of modern life. Letting metabolic syndrome gain an upper hand can have disastrous consequences since people with the metabolic syndrome are at twice the risk of developing cardiovascular disease compared with those who don’t have the syndrome and experience a five-fold increased risk of type 2 diabetes.¹

Metabolic syndrome is defined as a cluster of metabolic abnormalities found to be associated with a risk of coronary heart disease, stroke, and cardiovascular mortality greater than the risk of its individual components.² This clustering of metabolic abnormalities can vary slightly depending upon which report is used to describe the syndrome. The World Health Organization, the European Group for the Study of Insulin Resistance, and the American College of Endocrinology all have named similar but slightly different components. However, taking a composite of each of these definitions, the main components of metabolic syndrome are generally classified as elevated triglycerides, reduced HDL cholesterol, hypertension, and high blood sugar. Many individuals who have metabolic syndrome have insulin resistance, which predisposes them to pre-diabetes or type 2 diabetes. Obesity in general and physical inactivity are known to cause the syndrome, but it takes a second set of factors to trigger its accelerated onset the vast majority of the time. Top among this second set of factors is visceral fat.

As we reported in the last newsletter, abdominal fat is actually comprised of two metabolically distinct fat compartments. The fat that accumulates under the skin is called subcutaneous fat and is relatively benign. However, the dense visceral fat found deep in the abdomen, surrounding the intra-abdominal organs, is the type of fat linked most strongly with the metabolic syndrome as well as heightened cancer risk.

The prevalence of metabolic syndrome is alarmingly high to the point where one group of researchers called it a “pandemic.” Approximately one-third of the U.S. population suffers from each of the risk factors for metabolic syndrome. Furthermore, the prevalence of metabolic syndrome in the U.S. increased from 50 million Americans in 1990 to 64 million in 2000. This increase is thought to be due in part to an increase in obesity. From 1988 to 1994, the prevalence of obesity was 22.5 percent, but by 1999 to 2000 it had increased to 30.5 percent. Furthermore, the prevalence of the metabolic syndrome rises with the aging of the population due largely to age-related rises in blood pressure and glucose.¹

Even more alarming is the increase in metabolic syndrome among children and adolescents. This is due to the increase in obesity in this age group with about 16 percent of female children and teenagers in the U.S. and 18 percent of young males classified as overweight.¹

Setting the Stage for a Deadly Condition

The metabolic syndrome originates within the human body long before the various components manifest themselves. Lifestyle factors can set the stage for the metabolic dysfunction and accumulation of visceral fat that leads to the syndrome. Work stress has been significantly correlated with the metabolic syndrome and heart disease. When researchers studied 10,308 London-based male and female civil servants ages 35-55, chronic work stress was associated with coronary heart disease and with the development of metabolic syndrome and its components. There was also an association between work stress and factors related to the development of the metabolic syndrome including low physical activity and poor diet. Around 32 percent of the effect of work stress on coronary heart disease was attributable to its effect on health behaviors and the metabolic syndrome.³

Visceral Fat and Metabolic Abnormalities

The theories on what definitively causes metabolic syndrome have evolved over the years. In 1998, the WHO task force on diabetes named insulin resistance as the predominant cause, resulting in the syndrome being given the alternate name of insulin resistance syndrome. However, evidence has begun to accumulate that visceral fat plays a critical role in the development. The National Cholesterol Education Program (NCEP) has now replaced insulin resistance with increased waist circumference (abdominal obesity) as the diagnostic criteria.

In fact, visceral obesity and obesity in general are considered contributory factors in the development of insulin resistance, creating a viscous cycle that begins with increased stress and cravings, leading to consumption of poor food choices and reduced physical activity, which leads to the accumulation of visceral fat and consequently the development of insulin resistance and the metabolic syndrome.

Fat tissue secretes several inflammatory and immune mediators known as adipokines. When abdominal fat accumulates and adipokine secretion is increased, it predisposes individuals to the dangerous consequences that occur in metabolic syndrome including insulin resistance, increased risk of diabetes, and cardiovascular disease.⁴

Research has demonstrated it is actually visceral fat that predisposes an individual to develop the metabolic syndrome. For example, in a study of obese children, total fat was a significant and independent determinant of insulin resistance, but it was not a determinant of metabolic syndrome. Only visceral fat and insulin resistance were significantly related to the syndrome.⁵

Other researchers have concluded that in women, visceral fat accumulation “may be the immediate underlying factor that links risk factors for myocardial infarctions [heart attacks] to form the metabolic syndrome. Insulin resistance, which has been generally accepted to be the underlying factor, may be a component of the syndrome rather than its underlying link.”⁶

While visceral fat accumulation leads to metabolic syndrome, visceral fat reduction results in improvements in the various components. The benefits of visceral fat loss are thought to be due in part to the reduction in adipocytokine retinol binding protein-4 (RBP4), a protein recently shown to link obesity and insulin resistance.

One group of researchers theorized, “The relationship between individual changes in RBP4 and abdominal visceral fat indicated that RBP4 may be involved in the beneficial effect of visceral fat reduction on the improvement of insulin resistance and metabolic syndrome.”⁷

Further cementing the role of visceral fat in the metabolic syndrome was a study in aging rodents that showed surgical removal of visceral fat resulted in restoration of insulin action to levels of young rats. In rats genetically predisposed to develop diabetes, removal of visceral fat prevented the decrease in insulin action and delayed the onset of diabetes.

According to the researchers, “Our data suggest that insulin resistance and the development of diabetes can be significantly reduced in aging rats by preventing the age-dependent accumulation of visceral fat. This study documents a cause-and-effect relationship between visceral fat and major components of the metabolic syndrome.”⁸

Abdominal fat is strongly linked to other components of the metabolic syndrome. For example, a low concentration of HDL (the “good”) cholesterol is a common feature of people with abdominal obesity. Low HDL levels are of particular concern because the increased risk of cardiovascular disease that occurs when HDL levels are low persists even when the levels of LDL (the “bad”) cholesterol are dramatically reduced. HDL is known to promote the exit of cholesterol from cells, minimizing the accumulation of foam cells in the artery wall. HDLs also act as antioxidants and anti-inflammatory agents.⁹

Eliminating Visceral Fat

A new supplement known as Glabrinex™ has been shown to shrink visceral fat deposits, thereby minimizing an important cause of metabolic syndrome. This proprietary lipid-soluble extract of Glycyrrhiza glabra root, standardized for bioactive polyphenol flavonoid compounds and the unique licorice-derived flavonoid glabridin, has been tested in human and animal studies.

Researchers conducted an 8-week, placebo-controlled study to test 300 mg, 600 mg, and 900 mg per day doses of Glabrinex in overweight subjects. In the 900 mg group, significant decreases from baseline were observed in body weight and body mass index after 4 to 8 weeks. Furthermore, there was a significant reduction in visceral fat after 8 weeks with the 900 mg dose. In all three dosage groups, significant decreases from baseline occurred in fat mass after 8 weeks. These same effects did not occur in the placebo group.¹⁰

Another study included 103 healthy but moderately overweight subjects (63 men and 40 women) between 24 and 64 years of age. In the randomized, double-blind, placebo-controlled trial, subjects were randomly divided into one of two groups. One group consumed one capsule of Glabrinex (300 mg) for 12 weeks, the other group consumed a placebo.

The results showed that the mean body weight in the placebo group gradually increased over time. In contrast, body weight in the Glabrinex group was significantly suppressed at weeks 4, 8 and 12.¹⁰

In obese mice, Glabrinex reduced the weight of abdominal fat tissue and body weight gain. Examination revealed that fat cells shrank and the fatty degenerative state of liver cells improved in the animals given Glabrinex.¹¹

In obese diabetic mice fed a high-fat diet, Glabrinex lowered both abdominal fat and blood sugar. This led the study authors to declare, “This result indicated that LFO [licorice flavonoid oil] was effective in preventing diabetes and obesity, particularly visceral fat accumulation. Licorice flavonoids may be useful for improving visceral fat obesity in preventing the metabolic syndrome including type 2 diabetes.”¹²

An excessive ingestion study where subjects consumed 1,800 mg per day showed Glabrinex to be safe with few reported side effects.

Conclusion

The prevalence of metabolic syndrome is increasing at a disturbing rate, especially given the association between this syndrome and cardiovascular disease. Accumulation of visceral fat is strongly linked to the development of metabolic syndrome. Therefore, reducing visceral fat accumulation is a critical step in stopping the development of the syndrome. Glabrinex, which contains bioactive polyphenol flavonoid compounds and the unique licorice-derived flavonoid glabridin, has been shown to suppress abdominal fat.

Because fat is the reservoir for fat-soluble toxins, when mobilizing fat during weight loss, it is essential that a good liver support supplement such as HepatoGen™ be consumed along with an antioxidant supplement such as Extension Antioxidant.

References

1. Grundy SM. Metabolic Syndrome Pandemic. Arterioscler Thromb Vasc Biol. 2008 April; 28;629-36.

2. Cameron AJ, Shaw JE, Zimmet PZ. The metabolic syndrome: prevalence in worldwide populations. Endocrinol. Metab Clin N Amer. 2006;33(2):351-375.

3. Chandola T, Britton A, Brunner E, Hemingway H, Malik M, Kumari M, Badrick E, Kivimaki M, Marmot M. Work stress and coronary heart disease: what are the mechanisms? Eur Heart J. 2008 Mar;29(5):640-8, Eur Heart J. 2008 Mar;29(5):579-80.

4. Phillips LK, Prins JB. The link between abdominal obesity and the metabolic syndrome. Curr Hypertens Rep. 2008 Apr;10(2):156-64.

5. Druet C, Baltakse V, Chevenne D, Dorgeret S, Zaccaria I, Wang Y, Levy-Marchal C. Independent effect of visceral adipose tissue on metabolic syndrome in obese adolescents. Horm Res. 2008;70(1):22-8.

6. Phillips GB, Jing T, Heymsfield SB. Does insulin resistance, visceral adiposity, or a sex hormone alteration underlie the metabolic syndrome? Studies in women. Metabolism. 2008 Jun;57(6):838-44.

7. Lee JW, Lee HR, Shim JY, Im JA, Lee DC. Abdominal Visceral Fat Reduction Is Associated with Favorable Changes of Serum Retinol Binding Protein-4 in Nondiabetic Subjects. Endocr J. 2008 May 21. [Epub ahead of print].

8. Gabriely I, Ma XH, Yang XM, Atzmon G, Rajala MW, Berg AH, Scherer P, Rossetti L, Barzilai N. Removal of Visceral Fat Prevents Insulin Resistance and Glucose Intolerance of Aging. An Adipokine-Mediated Process? Diabetes. 2002;51:2951-2958.

9. Barter PJ. Metabolic Abnormalities in People with Abdominal Obesity: Low Levels of High-Density Lipoproteins. International Chair on Cardiometabolic Risk – News Item. May 16, 2008. Accessed online at www.cardiometabolic-risk.org.

10. Tominaga Y, Mae T, Kitano M, Sakamoto Y, Ikematsu H, Nakagawa K. Licorice flavonoid oil effects body weight loss by reduction of body fat mass in overweight subjects. J Health Sci. 2006;52(6):672-683.

11. Aoki, F, Honda, S, Kishida, H, Kitano,M, Arai, N, Tanaka, H, Yokota, S, Nakagawa, K, Asakura, T, Nakai, Y, and Mae, T. Suppression by licorice flavonoids of abdominal fat accumulation and body weight gain in high-fat diet-induced obese C57BL/6J mice. Biosci Biotechnol Biochem. 2007;71(1):206-214.

12. Nakagawa, K, Kishida, H, Arai, N, Nishiyama, T, and Mae, T. Licorice flavonoids suppress abdominal fat accumulation and an increase in blood glucose level in obese KK-A mice. Biol Pharm Bull. 2004;27(11):1775-1778.

The strength of the immune response changes based on several variables such as diet, stress, and mood. Thus, around the holidays, when people are more prone to eat sugary foods and refined carbohydrates, there is a direct and unfavorable effect on immune function. In addition, the stress of the holiday season can also have detrimental effects on the immune response. Adults average 2-4 colds per year, with increased occurrence during the fall and winter when the air is colder with decreased humidity.¹ Consequently, many people have an increased susceptibility to colds and flu during the holiday season.

Sugar and the Immune System

Animal models have shown that increasing sucrose intake increases the neurotransmitter serotonin, important for mood balancing, suggesting that eating sugar can make us feel better when depressed.² Although consuming sugar may result in enhanced mood, anyone who experiences this “sugar high” must pay a steep price. This is because numerous studies have shown that increased sugar intake dramatically decreases the immune response.

Short-term hyperglycemia (elevated blood sugar) affects all major components of innate immunity and impairs the ability of the individual to fight infection.³ The white blood cells are the primary mediators of the immune response. Neutrophils are a type of white blood cell that act as an important first-line-of-defense in the immune system by engulfing (phagocytizing) pathogens. Hyperglycemia has been shown to decrease neutrophil activity in numerous studies.4 One study showed that increased glucose levels decreased neutrophils’ ability to engulf several pathogens such as Staphylococcus epidermidis, Staphylococcus aureus, and Escherichia coli.⁵ A similar study showed that poor blood sugar control in diabetic patients decreased neutrophil activity against Klebsiella pneumoniae.⁶ Specifically, neutrophils experienced a decrease in their movement and their ability to engulf and kill pathogens, an increase in leukocyte apoptosis (programmed cell death), and a reduction in lymph node retention capacity. Additionally, lowering of blood glucose has been shown to significantly improve neutrophil activity.⁷

Sugar’s harmful effect on the immune system was further demonstrated in a study that showed a significant decrease in neutrophil activity in blood samples from healthy adults at 30 and 60 minutes following ingestion of 75 grams of glucose.⁸ Another similar study examined the activity of neutrophils after a 100 gram dose of various simple carbohydrates including glucose, fructose, sucrose, honey, and orange juice in humans. The results indicated that all simple carbohydrates tested significantly decreased the capacity of neutrophils to engulf bacteria. The greatest effects occurred between 1 and 2 hours after ingestion of the carbohydrates, and the values were still significantly below the fasting control values five hours after glucose ingestion.⁹ Thus, increasing intake of sugary foods will have a profound impact on the immune response.

Stress and the Immune System

Around the holidays, not only do individuals increase their consumption of sugary foods, they also often experience increased stress levels. Stress, through the hypothalamic-pituitary-adrenal (HPA) axis, can modulate the immune system. Cortisol, released from the adrenal glands, is the primary hormone that mediates the stress response. Cortisol, in response to stress, suppresses the immune response.¹⁰ Research has shown that stress can affect the immune system in several ways such as reduced neutrophil activity, changes in types of chemical mediators (cytokines) produced by the white blood cells, and decreased cytotoxic T-lymphocytes and natural killer cell activities.^11-12 Studies suggest that an elevated cortisol:DHEA ratio is a contributing factor to this reduced immunity, particularly in elderly patients. DHEA (dehydroepiandrosterone) is a steroid hormone secreted from the adrenal glands). More specifically, an elevated cortisol:DHEA ratio significantly decreases neutrophil activity.

One particularly interesting study evaluated the perceived life stress and risk of upper respiratory infections (URI). The study found that those individuals with high levels of negative life events and who showed high cortisol reactivity had increased numbers of URIs. Also this study showed that during times of increased perceived stress, lower reactivity of natural killer cells and CD8 T-lymphocytes were also correlated with increased URIs.¹³

In addition, studies have shown that anxiety affects immune function. Anxious subjects were found to have increased cortisol levels with impaired immune function and changes in cytokines released from the white blood cells.¹⁴

When Defenses are Down

EpiCor® is widely used for its ability to act as a potent immune system modulator. It has been shown to modulate the number and activity of immune cells known as lymphocytes including T-lymphocytes and natural killer cells, as well as antibody production.¹⁵ Additionally, EpiCor has been shown to significantly decrease the duration and number of reported symptoms in individuals suffering from colds and flu in a clinical trial.¹⁶ However, under times of increased vulnerability and decreased resistance to infection, such as during the holidays, pathogens may gain the upper hand. Consequently, even those individuals who regularly take Epicor for immune enhancement may need additional support this time of year. When defenses are down and the first signs of a cold or flu are felt, adding Fast Response™ can be a particularly powerful tool to enhance immunity.

Fast Response supports the immune system using a combination of vitamins and minerals with traditional Chinese herbs. These ingredients modulate white blood cells including B-lymphocytes, T-lymphocytes, macrophages, and natural killer cells, as well as decrease inflammation, which causes many of the symptoms associated with colds and flu.

The traditional Chinese botanicals in Fast Response have shown efficacy in supporting immunity. Forsythia suspense has been shown to have anti-viral and anti-bacterial activity.^17-18 Lonicera japonicus inhibits the pro-inflammatory cyclooxygenase (COX)-2 and 5-lipoxygenase (LOX) enzymes,¹⁹ which is important as infection with the cold virus increases the activity of these two inflammatory enzymes.²⁰ In traditional Chinese medicine, Platycodon grandiflorum has been used for clearing the lungs, resolving phlegm, and soothing the throat,²¹ and research has shown that constituents of Platycodon stimulate macrophage proliferation and activity.²² Arctium lappa (Burdock) contains arctigenin, which has been shown to prolong the survival time of mice infected with influenza virus as well as inhibited lung consolidation in mice pneumonia caused by the influenza virus.²³ Arctium lappa decreases coughing, and was equally active as some synthetic preparations in studies using animal models.²⁴ Research indicates that both Arctium lappa and the essential oils of Mentha arvenis inhibit the growth of several strains of pathogenic bacteria.^25-26 Constituents of Glycyrrhizae uralensis have anti-inflammatory properties,²⁷ can activate macrophages,²⁸ and have been shown to decrease replication of coronavirus from patients with severe acute respiratory syndrome (SARS).²⁹ Schizonepeta tenuifolia has been shown to regulate inflammatory responses by modulating T-lymphocyte activity.³⁰ This combination of nutrients and botanicals can provide the extra support needed during times of increased vulnerability to colds and flu.

Taking a formula that combines the above botanicals with immune-supporting vitamins and minerals can be a particularly effective approach. Vitamins A, C, B₆ and the mineral zinc are critical for optimal immune function. Vitamin A is required for the growth and activation of B-lymphocytes, increases macrophage activity, and is important in maintaining a sufficient level of natural killer cells. Deficient levels of Vitamin A can reduce lymphocyte numbers, natural killer cells, immunoglobulin responses, and impair T-lymphocyte function.³¹ Vitamin C has been shown in multiple studies to significantly reduce the duration of episodes and the severity of common cold and flu symptoms.³² Vitamin B₆ is important for normal immune function as deficiencies have been shown to alter lymphocyte differentiation and maturation and impair antibody production.³³ Zinc is required for normal development and function of white blood cells such as neutrophils and natural killer cells, and zinc deficiency adversely affects T-lymphocyte function, B-lymphocyte development, antibody production, and macrophage activity.³⁴ Clinical trials indicate that zinc supplementation can significantly shorten the time to complete resolution of symptoms in patients with the common cold.³⁵

Adding a vitamin D3 supplement to the immune-boosting regimen above also is important during cold and flu season. Researchers have theorized that the reason why the cold and flu season occurs in winter is because vitamin D deficiency is widespread during this time of year when exposure to sunlight is minimal.³⁶ One explanation for vitamin D’s role in immunity is that it up-regulates an important gene called cathelicidin, a naturally occurring broad-spectrum antibiotic.³⁷

Conclusion

Stress and poor dietary habits such as increasing intake of sugary foods and refined carbohydrates increase susceptibility to infection, particularly this time of year. Supplements such as EpiCor are ideal for general immune support. However, under times of increased vulnerability and decreased resistance to infection, products such as Fast Response may be necessary for extra immune enhancement. Adding a vitamin D3 supplement to this regimen will further strengthen immunity and provide additional defense against colds and influenzas.

References

1. National Institutes of Health. Common Cold. Available at: http://www3.niaid.nih.gov/topics/commonCold/overview.htm. Accessed on: 09-22-08.

2. Smolders I, Loo JV, Sarre S, et al. Effects of dietary sucrose on hippocampal serotonin release: a microdialysis study in the freely-moving rat. Br J Nutr. 2001 Aug;86(2):151-5.

3. Turina M, Fry DE, Polk HC Jr. Acute hyperglycemia and the innate immune system: clinical, cellular, and molecular aspects. Crit Care Med. 2005 Jul;33(7):1624-33.

4. Patel KL. Impact of tight glucose control on postoperative infection rates and wound healing in cardiac surgery patients. J Wound Ostomy Continence Nurs. 2008 Jul-Aug;35(4):397-404.

5. Van Oss CJ. Influence of glucose levels on the in vitro phagocytosis of bacteria by human neutrophils. Infect Immun. 1971 Jul;4(1):54-9.

6. Lin JC, Siu LK, Fung CP, et al. Impaired phagocytosis of capsular serotypes K1 or K2 Klebsiella pneumoniae in type 2 diabetes mellitus patients with poor glycemic control. J Clin Endocrinol Metab. 2006 Aug;91(8):3084-7.

7. Alba-Loureiro TC, Munhoz CD, Martins JO, et al. Neutrophil function and metabolism in individuals with diabetes mellitus. Braz J Med Biol Res. 2007 Aug;40(8):1037-44.

8. Bernstein J, Alpert S, Nauss KM, et al. Depression of lymphocyte transformation following oral glucose ingestion. Am J Clin Nutr. 1977;30:613 (abstract).

9. Sanchez A, Reeser JL, Lau HS, et al. Role of sugars in human neutrophilic phagocytosis. Am J Clin Nutr. 1973 Nov;26(11):1180-4.

10. Butcher SK, Killampalli V, Lascelles D, et al. Raised cortisol:DHEAS ratios in the elderly after injury: potential impact upon neutrophil function and immunity. Aging Cell. 2005 Dec;4(6):319-24.

11. Reiche EM, Morimoto HK, Nunes SM. Stress and depression-induced immune dysfunction: implications for the development and progression of cancer. Int Rev Psychiatry. 2005 Dec;17(6):515-27.

12. Godbout JP, Glaser R. Stress-induced immune dysregulation: implications for wound healing, infectious disease and cancer. J Neuroimmune Pharmacol. 2006 Dec;1(4):421-7.

13. Cohen S, Hamrick N, Rodriguez MS, et al. Reactivity and vulnerability to stress-associated risk for upper respiratory illness. Psychosom Med. 2002 Mar-Apr;64(2):302-10.

14. Arranz L, Guayerbas N, De la Fuente M. Impairment of several immune functions in anxious women. J Psychosom Res. 2007 Jan;62(1):1-8.

15. Jensen GS, Hart AN, Schauss AG. An antiinflammatory immunogen from yeast culture induces activation and alters chemokine receptor expression on human natural killer cells and B lymphocytes in vitro. Nutrition Research. 2007 Jun;27(6):327-335.

16. Moyad MA, Robinson LE, Zawada ET Jr, et al. Effects of a modified yeast supplement on cold/flu symptoms. Urol Nurs. 2008 Feb;28(1):50-5.

17. Zhang GG, Song SJ, Ren J, et al. A new compound from Forsythia suspensa (Thunb.) Vahl with antiviral effect on RSV. J Herb Pharmacother. 2002;2(3):35-40.

18. Kong B, Wang J, Xiong YL. Antimicrobial activity of several herb and spice extracts in culture medium and in vacuum-packaged pork. J Food Prot. 2007 Mar;70(3):641-7.

19. Rall LC, Meydani SN. Vitamin B6 and immune competence. Nutr Rev. 1993 Aug;51(8):217-25.

20. Seymour ML, Gilby N, Bardin PG, et al. Rhinovirus infection increases 5-lipoxygenase and cyclooxygenase-2 in bronchial biopsy specimens from nonatopic subjects. J Infect Dis. 2002 Feb 15;185(4):540-4.

21. Guo L, Zhang C, Li L, et al. Advances in studies on Platycodon grandiflorum. Zhongguo Zhong Yao Za Zhi. 2007 Feb;32(3):181-6.

22. Choi CY, Kim JY, Kim YS, et al. Augmentation of macrophage functions by an aqueous extract isolated from Platycodon grandiflorum. Cancer Lett. 2001 May 10;166(1):17-25.

23. Yang Z, Liu N, Huang B, et al. Effect of anti-influenza virus of Arctigenin in vivo. Zhong Yao Cai. 2005 Nov;28(11):1012-4.

24. Kardosová A, Ebringerová A, Alföldi J, et al. A biologically active fructan from the roots of Arctium lappa L., var. Herkules. Int J Biol Macromol. 2003 Nov;33(1-3):135-40.

25. Gentil M, Pereira JV, Sousa YT, et al. In vitro evaluation of the antibacterial activity of Arctium lappa as a phytotherapeutic agent used in intracanal dressings. Phytother Res. 2006 Mar;20(3):184-6.

26. Imai H, Osawa K, Yasuda H, et al. Inhibition by the essential oils of peppermint and spearmint of the growth of pathogenic bacteria. Microbios. 2001;106 Suppl 1:31-9.

27. Shin EM, Zhou HY, Guo LY, et al. Anti-inflammatory effects of glycyrol isolated from Glycyrrhiza uralensis (Leguminosae) in LPS-induced RAW264.7 macrophages. Int Immunopharmacol 2008 Jul 10. Published online ahead of print.

28. Nose M, Terawaki K, Oguri K, et al. Activation of macrophages by crude polysaccharide fractions obtained from shoots of Glycyrrhiza glabra and hairy roots of Glycyrrhiza uralensis in vitro. Biol Pharm Bull. 1998 Oct;21(10):1110-2.

29. Cinatl J, Morgenstern B, Bauer G, et al. Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet. 2003 Jun 14;361(9374):2045-6.

30. Kang H, Oh YJ, Choi HY, et al. Immunomodulatory effect of Schizonepeta tenuifolia water extract on mouse Th1/Th2 cytokine production in-vivo and in-vitro. J Pharm Pharmacol. 2008 Jul;60(7):901-7.

31. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2002. Available at: www.nap.edu/books/0309072794/html/.

32. Gorton HC, Jarvis K. The effectiveness of vitamin C in preventing and relieving the symptoms of virus-induced respiratory infections. J Manipulative Physiol Ther. 1999 Oct;22(8):530-3.

33. Rall LC, Meydani SN. Vitamin B6 and immune competence. Nutr Rev. 1993 Aug;51(8):217-25.

34. Shankar AH, Prasad AS. Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr. 1998 Aug;68(2 Suppl):447S-463S.

35. Mossad SB, Macknin ML, Medendorp SV, et al. Zinc gluconate lozenges for treating the common cold. A randomized, double-blind, placebo-controlled study. Ann Intern Med. 1996 Jul 15;125(2):81-8.

36. Cannell JJ, Vieth R, Umhau JC, Holick MF, Grant WB, Madronich S, Garland CF, Giovannucci E. Epidemic influenza and vitamin D. Epidemiol Infect. 2006 Dec;134(6):1129-40.

37. Cannell JJ, Hollis BW. Use of vitamin D in clinical practice. Altern Med Rev. 2008 Mar;13(1):6-20.

The liver is the largest digestive gland in the human body. It has over 500 known functions, including synthesizing proteins, producing bile, detoxifying drugs, producing cholesterol, maintaining healthy glucose levels in the blood, and storing minerals and vitamins. The liver’s detoxification process is arguably its most important function, which includes detoxifying prescription drugs, dietary ingredients, alcohol and almost any organic molecules in our diet.¹

Liver health is important not only to individuals who have a liver disease, but also to people who 1) Want to protect the liver from environmental toxins; 2) Are experiencing symptoms that might be a sign of a sluggish liver such as fatigue, allergies, constipation, intolerance to fatty foods, poor complexion, elevated cholesterol and triglycerides and intolerance to alcohol; 3) Are participating in a weight loss program, since fat is a reservoir for fat soluble toxins that are processed through the liver (see metabolic syndrome article in this newsletter to learn more about visceral fat and weight loss) and 4) Are frequently indulging in alcohol consumption, especially around the holidays when alcohol consumption is increased.

The Body’s Great Detoxifier

Lipid peroxidation, the process of damage to the fatty acids in cell membranes, is the primary cause of liver damage, which is due to free radicals, whether generated by liver disease, detoxification reactions, alcohol or natural metabolic processes. Many of the free radicals originate in the mitochondria of liver cells, but many free radicals are byproducts of the enormous chemical reactions happening inside the liver during the detoxification process.²

The liver detoxification process occurs in two stages. Phase I detoxification is the liver’s oxidation of organic molecules from the bloodstream to break these molecules into smaller, sometimes more toxic intermediates. These intermediates are then combined with glutathione through the action of enzymes called glutathione transferases (GSTs). This process is referred to as Phase II detoxification. Glutathione transferases make glutathione react with these toxic intermediates to make them harmless molecules that are then excreted in the urine and feces.³

The central problem for optimal healthy liver detoxification is that the liver is not producing enough glutathione transferases (GSTs) or manufacturing enough glutathione to neutralize the Phase I metabolites generated. This is particularly true in the cases of liver disease where glutathione depletion often occurs. In a perfect world, the liver would produce enough GSTs and glutathione in Phase II detoxification to neutralize all the Phase I metabolites it produces, but this is not always, or even usually, the case.³

Phase I metabolites are often free radicals referred to as “electrophiles,” or compounds missing a paired electron, making them highly reactive molecules that can damage DNA and other essential proteins in the body, and which eventually can lead to cancer or cirrhosis of the liver.⁴ In 1984, Richard Cutler, the chief scientist of the Gerontology NIH Research Center, collected data from around the world, including zoos and veterinary records to determine the average lifespan data available on all mammals, including man. Cutler then measured the antioxidants and enzymes that led mammals to have longer lifespans. He found that the second most important molecule in longer-lived mammals (including man), which correlated with greater longevity, was higher liver glutathione transferase levels.⁵

Many viral infections, including hepatitis A, B and C, contribute to liver disease and are implicated in raising liver enzymes such as AST and ALT that signal liver damage while lowering key protective liver enzymes and glutathione.⁶

When the liver isn’t able to optimally perform, liver disease can manifest itself in many ways. Typical clinical manifestations include jaundice, liver failure, liver enlargement, cholestasis (blockage or slowing of bile flow), portal hypertension (high blood pressure in veins that transport blood from the intestines to the liver), and hepatic encephalopathy, a buildup of toxins in the brain. Fatigue, weight loss and feelings of sickness can be confused with other diseases or overlooked in the earlier stages of liver disease.⁷

Liver diseases include hepatitis, which can develop into cancer and cirrhosis⁷; sluggish liver, another name for subclinical liver dysfunction or minimal loss of liver function; and fatty liver or hepatic steatosis, caused by alcohol and drug ingestion that results in fat deposition in the liver.⁷ Fatty liver, the collection of excessive amounts of triglycerides and other fats inside liver cells, can be either a long-term or a temporary condition. It is reversible once the cause of the problem is diagnosed. However, if left untreated, it can contribute to other issues, like lipid peroxidation, or liver cell membrane damage. When the liver can no longer store more triglycerides, it releases these fats into the bloodstream, resulting in elevated serum triglycerides, a serious heart disease risk factor.⁷

Supporting Healthy Liver Function

The most obvious questions involving the optimal maintenance of liver health revolve around what supplements can block lipid peroxidation in the liver, stimulate higher liver glutathione transferase levels and maintain normal liver glutathione levels?

A formula (such as HepatoGen™) that contains vitamin C, benfotiamine, artichoke extract, lipoic acid, milk thistle, N-acetyl cysteine, and Scutellaria baicalensis root can be particularly effective at helping the liver function optimally. Vitamin C is a critical nutrient in the liver, especially during the Phase I detoxification process, which is also referred to as the monoxygenase system, the step where free radicals, or electrophiles, are generated. Use of combined antioxidants including vitamin C showed great promise in liver diseases of different causes.8 Benfotiamine, a highly bioavailable form of thiamine, has been highly effective in blocking glycation in diabetics and liver damage in alcoholics. The liver and kidney are the organs that receive the highest concentrations of benfotiamine.⁹

Other substances shown to improve liver health include whole artichoke extract¹⁰; Lipoic acid, a potent free radical scavenger, metal chelator and regenerator of other key antioxidants (such as glutathione) that has been found to increase apoptosis (cellular suicide) in human liver cell lines¹¹; Milk thistle extracts, studied in human trials for possible beneficial effects on liver diseases, hepatitis C and high cholesterol¹²; and N-acetyl cysteine (NAC), critical for liver glutathione synthesis, an important function since glutathione is usually depleted in chronic and acute liver disease and is necessary for Phase II liver detoxification.13 NAC has been used as a supportive therapy in acute viral hepatitis, acute liver failure, and non-alcoholic fatty liver disease. It also has been used to support the health of chronic hepatitis B and C patients.^13-16

The botanical Scutellaria baicalens can work synergistically with the above substances to enhance liver health. The Scutellaria baicalensis component baicalin, when given to rats exposed to toxic, high doses of acetaminophen, prevented many of the toxic effects observed in rats given acetaminophen without baicalin. Furthermore, none of the rats given baicalin with acetaminophen died, whereas 43 percent of the rats given only acetaminophen died. Baicalin also prevented the acetaminophen-related drop in levels of glutathione.¹⁷

Alcohol Defense

Individuals who regularly drink alcohol or who tend to indulge in extra alcoholic beverages around the holidays can help protect the liver by consuming a synergistic blend of liver-protective substances such as kudzu and pyroglutamic acid (found in Intox Rx). Even if alcohol consumption is limited to one or two glasses of red wine a few times per week, the benefits of the resveratrol in the wine can be maximized by ensuring that the liver is protected from the adverse effects of the alcohol.

In human and animal studies, kudzu suppresses free-choice ethanol intake.¹⁸ In a 2005 trial of kudzu in male and female “heavy drinkers,” subjects consumed either a kudzu extract or placebo for seven days. Participants served as their own controls. Kudzu consumption resulted in a significant reduction in beers consumed and the time taken to consume each beer. There was no significant change in the urge to drink alcohol and no reported side effects.¹⁹

Pyroglutamic acid is another novel liver-supporting substance studied in a number of human trial.²⁰ In one study, a double-blind, placebo-controlled trial of 58 subjects consuming pyroglutamic acid, the researchers concluded pyroglutamic acid “significantly decreased the half-life of ethanol in blood and showed a faster rate of ethanol elimination. The effects of ethanol half-life in blood were accompanied by a faster onset of recovery from intoxication.”²¹

Conclusion

Liver function is affected by a number of factors including environmental toxins, weight loss, alcohol consumption and normal metabolic processes. Using a formula such as HepatoGen, which contains vitamin C, benfotiamine, artichoke extract, lipoic acid, milk thistle, N-acetyl cysteine, and Scutellaria baicalensis, can protect this vitally important organ against these damaging processes. Around the holidays and anytime alcohol is consumed regularly, adding kudzu and pyroglutamic acid (Intox Rx) to the above regimen can provide additional liver support.

References

1. Introduction: Liver Function, The Merck Manual, 2006 edition, revised by Sidney Cohen, MD

2. Barry OP, Burke ALucey MRLawson JA, Rokach J, FitzGerald GAJ. Alcohol-induced generation of lipid peroxidation products in humans. Clin Invest. 1999 Sep; 104 (6):805-13.

3. Dourado DF, Fernandes PA, Ramos MJ. Mammalian cytosolic glutathione transferases. Curr Protein Pept Sci. 2008 Aug;9(4):325-331.

4. On the Detoxification Functions of The Liver in Healthy Subjects and Those with Liver Diseases. Hippokrates. 1964 May 31; 35:388-94.

5. Cutler RG. Antioxidants and aging. Am J Clin Nutr. 1991 Jan; 53 (1 Suppl):373S-379S.

6. Vazquez E, Gerez E, Caballero F, Polo C, Batlle A. Drug metabolizing enzyme system and heme pathway in hepatocarcinogenesis. Cancer Biochem Biophys. 1999 Jul;17(1-2):25-34.

7. Schiff’s Diseases of the Liver. Authors: EE. Schiff, MD, Michael Sorell, MD, Publisher, Lippincott, Williams. 2006.

8. Zaidi SM, Al-Qirim TM, Banu N. Effects of antioxidant vitamins on glutathione d epletion and lipid peroxidation. Drugs R D. 2005; 6 (3): 157-65.

9. Anisimova EI, Danilov AB. Benfotiamine efficacy in alcoholic polyneuropathy therapy. Zh Nevrol Psikhiatr Im S S Korsakova. 2001;101:(12): 32-6.

10. Pelt JM. Medicine’s green revolution. UNESCO Cour. 1979 Jul; 8-16.

11. Malinska D, Winiarska K. Lipoic acid: characteristics and therapeutic application. Postepy Hig Dosw. 2005; 59: 535-43.

12. Tamayo C, Diamond S. Review of clinical trials evaluating safety and efficacy of milk thistle (Silybum marianum. Integr Cancer Ther. 2007 Jun;6(2):146-57.

13. De Flora S, Cesarone CF, Balansky RM, et al. Chemopreventive properties and mechanisms of N-acetyl cysteine. The experimental bac kground. J Cell Biochem Suppl. 1995; 33-41.

14. Pamuk GE, Sonsuz A. N-acetylcysteine in the treatment of non-alcoholic steatohepatitis. J Gastroenterol Hepatol. 2003 Oct;18(10):1220-1.

15. Bonkovsky HL. Therapy of hepatitis C; other options. Hepatology. 1997 Sep; 26 (3):143S-151S.

16. Shi XF, Guo SH, Wu G, Mao Q, et al. A multicenter clinical study of N-acetylcysteine on chronic hepatitis B. Zhonhua, Gan Zang Bing Za Zhi. 2005 Jan; 13 (1):20-3.

17. Jang SI, Kim HJ, Hwang KM, Jekal SJ, Pae HO, Choi BM, Yun YG, Kwon TO, Chung HT, Kim YC. Hepatoprotective effect of baicalin, a major flavone from Scutellaria radix, on acetaminophen-induced liver injury in mice. Immunopharmacol Immunotoxicol. 2003 Nov;25(4):585-94.

18. Keung WM, Vallee BL. Kudzu root: an ancient Chinese source of modern antipsotropic agents. Phytochemistry. 1998 Feb; 47(4):499-506.

19. Lukas SE, Penetar D, Berko J, et al. An extract of the Chinese herbal root kudzu reduces alcohol drinking by heavy drinkers in a naturalistic setting. Alcohol Clin Exp Res. 2005 May; 29(95): 756-62.

20. Cabellaria J, Pares A, Bru C, Mercader J, et al. Metadoxine accelerates fatty liver recovery in alcoholic patients; the results of a randomized double-blind, placebo-control trial. Spanish Group for the Study of Alcoholic Fatty liver. J Hepatol. 1998;28(1);54-60.

21. Shpilenya L, Muzychenko AP, Gasbarrini G, Addolorato G. Metadoxine in acute alcohol intoxication: a double-blind, randomized, placebo-controlled study. Alcohol Clin Exp Res. 2002 Mar;26(3):340-6.

For individuals with poor digestion or sensitivities, or who simply prefer a liquid, a new Vitamin D3 liquid is a simple and pleasant way to augment intake of this important nutrient. Each 1 ml dropper provides 5,000 IU of pure vitamin D3 in a base of hypoallergenic MCT oil, which has been studied for its effects on weight loss and appetite control. Tasteless and odorless, Vitamin D3 liquid can be administered directly from the dropper, added to other foods or liquids or used topically for skin ailments.

Since the early 20th century, vitamin D has been recognized for its essential role in bone growth and mineralization. Now, vitamin D is emerging as the “wonder nutrient” of the 21st century. Current research confirms vitamin D’s importance in a variety of applications including cardiovascular health, joint health, immunity, cognitive function, mood enhancement, blood sugar control, fertility and bowel health.

Vitamin D is produced in the skin by ultraviolet energy in sunlight triggering the conversion of 7-dehydrocholesterol, found in the basal layers of the skin, to cholecalciferol. Processes in the liver and kidneys then convert cholecalciferol to the bioactive form, 1,25(OH)2D3, also known as calcitriol.

Dietary sources are relatively scarce, the flesh of fatty fish being the only significant source of cholecalciferol. Prior to the widespread fortification of foods, people, other than those living in fishing communities, were completely dependent on sunlight exposure for their vitamin D sufficiency. The incidence of rickets, the highest-profile symptom of vitamin D deficiency, increased substantially in Europe as people moved from sunny rural environments to the relatively grim environs of polluted cities during the Industrial Revolution.¹

Although vitamin D fortification has largely eliminated frank vitamin D deficiency (as defined by the absence of rickets), a new standard for vitamin D sufficiency is now being recognized.² Exciting, new non calcium-related roles of vitamin D have been emerging as promising targets for nutrient therapy. Researchers are arguing for increased intakes, pointing out that dietary intakes of 2,000 to 10,000 IU daily are associated with greatly reduced rates of heart disease, cancer, stroke, hypertension, diabetes, osteoarthritis, autoimmune diseases and more.

Vitamin D affects this diverse group of biological functions by influencing gene expression. On entering the cell nucleus, vitamin D acts on a transcription factor called nuclear vitamin D receptor (VDR). Transcription factors are a group of proteins that read and interpret the genetic “blueprint” in the DNA and are vital for many important cellular processes.

VDR is part of a superfamily of steroid/thyroid hormone nuclear receptors, and is found in a variety of cell types, including immune, muscle, fat, bone marrow, cancer and pancreatic beta cells.³ When calcitriol enters the cell nucleus, it binds with VDR and is able to initiate transcription in as many as 50 different genes.⁴ Furthermore, a variant of VDR is found in certain cells that is able to trigger a non-genomic “rapid response” to vitamin D activation. Immediate biological responses can include release of insulin from beta cells and rapid migration of endothelial cells, a process crucial for re-establishing tissue integrity after vascular insult. Examples of functions controlled by VDR include:

Immunity

VDR is expressed on many immune cells, including B and T lymphocytes, and activated macrophages can produce their own calcitriol, pointing to an essential role for vitamin D in immunity. Vitamin D has been shown to enhance, through VDR transcription, CD4+ helper cell function as well as mucosal antibody response. Conversely, low vitamin D status is associated with diminished resistance to bacterial infection.⁵

Hypertension

Modulating the renin-angiotensin system (RAS) is a popular strategy for controlling hypertension. RAS drugs target inhibition of angiotensin converting enzyme (ACE) and blockade of the angiotensin type 1 (AT(1)) receptor. A feedback mechanism, however, limits the drug effectiveness by causing a compensatory increase in renin production. Administration of vitamin D can help to overcome the limitations of RAS-targeted therapy by effectively downregulating the expression of the gene that codes for renin. Clinical trials, epidemiological and mechanistic studies all confirm vitamin D’s value in controlling blood pressure.^6-7

Glucose Control

The renin-angiotensin (RAS) system responsible for controlling blood pressure also plays a key role in glucose metabolism. ACE inhibition and AT-1 blockade as mentioned above improve glucose transport and insulin signaling and improve insulin sensitivity. Large-scale clinical trials repeatedly demonstrated the ability of RAS inhibition to delay the onset of type 2 diabetes.⁸ Vitamin D can not only suppress RAS activity without triggering negative feedback, but also improves beta cell response via the rapid response mechanism mentioned earlier.

Vitamin D3 Plus MCT Oil

Combining vitamin D3 with MCT oil creates a unique synergy. MCTs (medium chain triglycerides) are healthy fats metabolized quickly in the liver. Studies have shown MCTs can increase energy expenditure while decreasing fat storage, supporting healthy weight and body composition. In one double-blind, controlled study, researchers found that in subjects with the highest body mass index, MCTs significantly decreased body weight and the area of subcutaneous fat at weeks four, eight and 12.⁹

References

1. National Academy of Sciences. Unraveling the Enigma of Vitamin D. http://ods.od.nih.gov/factsheets/vitamind.asp Accessed October 4, 2008.

2. Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008 Apr;87(4):1080S-6S.

3. Pinette KV, Yee YK, Amegadzie BY, Nagpal S. Vitamin D Receptor as a Drug Discovery. Target Mini Rev Med Chem. 2003 May;3(3):193-204.

4. Guyton KZ, Kensler TW, Posner GH. Vitamin D and vitamin D analogs as cancer chemopreventive agents. Nutr Rev. 2003 Jul;61(7):227-38.

5. Hayes CE, Nashold FE, Spach KM, Pedersen LB. The immunological functions of the vitamin D endocrine system. Cell Mol Biol (Noisy-le-grand). 2003 Mar;49(2):277-300.

6. Yuan W, Pan W, Kong J, Zheng W, Szeto FL, Wong KE, Cohen R, Klopot A, Zhang Z, Li YC. 1,25-dihydroxyvitamin D3 suppresses renin gene transcription by blocking the activity of the cyclic AMP response element in the renin gene promoter. J Biol Chem. 2007 Oct 12;282(41):29821-30.

7. Li YC, Qiao G, Uskokovic M, Xiang W, Zheng W, Kong J. Vitamin D: a negative endocrine regulator of the renin-angiotensin system and blood pressure. J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):387-92.

8. Scheen AJ. Renin-angiotensin system inhibition prevents type 2 diabetes mellitus. Part 1. A meta-analysis of randomised clinical trials. Diabetes Metab. 2004 Dec;30(6):487-96.

9. Tsuji H, Kasai M, Takeuchi H, Nakamura M, Okazaki M, Kondo K. Dietary medium-chain triacylglycerols suppress accumulation of body fat in a double-blind, controlled trial in healthy men and women. J Nutr. 2001 Nov;131(11):2853-9.

In the past I have touched upon the topic of dog food. This month I will go into more detail about what we are feeding our canine friends.

If you review past Pet Corners explaining what goes into dog food, you will understand that many different possible ingredients exist and the grades of those ingredients are just as variable.

Keep in mind that a dog food label tells you the content of the food along the lines of protein, carbohydrate and fat, but only partially lets you know the origin or ingredients that create that amount of protein, carbohydrate and fat. It is quite possible to get a high protein content using shoe leather, but the protein will be poorly digestible and nearly nonbioavailable. No one is going to tell you the exact source of the protein; however, they do list ingredients.

To get back to the ingredients, think of the cost of food. The best quality foods will have meat, a good source of carbohydrates and oil, which must have preservatives in order to keep them from going rancid. Typically, the lower the cost of the food, the lower the quality of the ingredients, so the lower cost food is not necessarily the biggest bargain. It is usual for a higher quality food to cost more. However, more often than not, the higher quality means you do not have to feed as much. The more the breakdown products of the food are available (bioavailable) to the body, the smaller the amount needed to keep your pet in prime condition.

Remember the problem we had about a year ago with pet foods causing problems with kidney function? This was caused because a Chinese company wanted to make their ingredient show a higher protein content so they added melamine. Melamine by itself is nontoxic in low doses, but when combined with cyanuric acid it can cause fatal kidney stones due to the formation of an insoluble melamine cyanurate. Melamine is described as being "Harmful if swallowed, inhaled or absorbed through the skin. Chronic exposure may cause cancer or reproductive damage. It is an eye, skin and respiratory irritant.” However, the toxic dose is on par with common table salt with an LD50 of more than 3 grams per kilogram of bodyweight. Now, babies in China are having the same problems our pets were having. Sadly, there have been a number of babies who have died from the ingestion of contaminated baby formula. This is all because of price, trying to make cheap ingredients look better than they really are.

When comparing the amount fed to maintain a healthy body, it is common for the better food to be cheaper on a cost per day basis. The other place where it tends to be cheaper is in the lack of veterinary bills. Feeding a high-quality food decreases the likelihood of illness. While it does not make veterinary bills go away, it is very likely to make them smaller and more routine.

Dogs that have chronic loose stools and respond poorly to treatment often respond to switching them to a good organic food such as Wenaewe®, which has no pesticides, herbicides, fertilizers or coloring agents included, and a probiotic such as BioPro™ that contains five different bacteria that are normally found in the bowel.

A dog’s diet also can be supplemented with Natural Whole Food Concentrate for Dogs. This product provides natural sources of healthy fats, fibers, protein, detoxifying herbs and carbohydrates that help dogs achieve a balanced diet. This is an excellent product to help your pet reach a higher level of vitality, staying happy and healthy for what is likely to be a longer life.

Studies conducted over the last 30 years have consistently linked elevated levels of the amino acid homocysteine with an increased risk for developing heart disease. These findings led one group of scientists to suggest that up to 50,000 deaths a year in the United States could be prevented by fortifying food supplies with folic acid, one of a number of B vitamins shown to reduce homocysteine levels.¹ Other researchers have estimated that two-thirds of all cases of hyperhomocystinemia are due to a deficiency of B vitamins.² In addition to cardiovascular disease, recent studies are now suggesting that elevated levels of homocysteine may play a role in such conditions as Alzheimers and Parkinsons diseases, rheumatoid arthritis, miscarriages, pregnancy-induced hypertension, diabetes, chronic fatigue syndrome and fibromyalgia.

Recent reports in scientific journals have raised the question - are elevated homocysteine levels due to a particular health condition, or are they the cause of ill health? This issue is being debated among scientists, along with the question of whether supplementation with B vitamins can provide protection against elevated homocysteine and disease.

Homocysteine Metabolism

Homocysteine is an amino acid formed from the metabolism of the essential amino acid, methionine. High dietary consumption of methionine, which can be found in meats and dairy products, can result in the overproduction of homocysteine. Once homocysteine is produced it is metabolized in the body through one of two possible pathways - remethylation or transsulfuration (Figure 1). Remethylation is a process that utilizes folate, vitamin B12 or betaine (trimethylglycine) to convert homocysteine back to methionine. Alternately, transsulfuration utilizes vitamin B6, pyridoxal-5-phosphate, to catabolize excess homocysteine into a number of metabolites for eventual excretion from the body. Plasma homocysteine concentrations may differ, depending on which metabolic homocysteine pathway is defective. Even a mildly impaired remethylation pathway will significantly increase plasma fasting homocysteine concentrations. This impairment may be caused by reduced levels of folate, vitamin B12 or genetic defects. In contrast, a mild impairment in the transsulfuration pathway can lead to a very slight increase in fasting plasma homocysteine levels. A transsulfuration impairment may be due to genetic defects or inadequate levels of vitamin B6. It is usually characterized by elevated plasma homocysteine following a methionine loading test, where scientists administer high doses of methionine to subjects and observe homocysteine levels.^3-5

Cause or Consequence?

An abundance of research indicates that an increased homocysteine level may indicate an increased risk of cardiovascular disease. One analysis of 27 studies involving more than 4,000 patients with cardiovascular diseases and the same number of controls showed that homocysteine was an independent risk factor for atherosclerotic disease in coronary, cerebral and peripheral vessels. It was estimated that for every 5-µM (micromole) increase in total homocysteine plasma levels there followed an increased risk of coronary heart disease of 60% for men and 80% for women.⁶

Other scientists came to a similar conclusion after reviewing 42 additional studies of homocysteine and cardiovascular disease mortality. Only six of these additional studies were not able to link elevated homocysteine with disease or mortality. The remainder showed a clear association with disease, including an increased risk of thrombosis. One convincing study examined cardiovascular disease patients for 4.6 years. During this period, only 3.6% of those with a homocysteine level less than 9µM died, whereas 24.7% of patients with a homocysteine greater than 15µM died. In a study that used physicians as subjects, baseline homocysteine concentrations were significantly higher in men who later had myocardial infarctions than in matched control subjects.^7-9

Recently, some research has contradicted homocysteines role in disease. At issue is whether homocysteine actually causes disease or if it is merely a consequence of cardiovascular conditions, diabetes, and other diseases.

In one review, scientists pointed out that many case-control studies have examined patients soon after a cardiovascular event, when homocysteine levels peak. Similarly, in the British Regional Heart Study, homocysteine level predicted stroke only in men with preexisting coronary heart disease.¹⁰ In patients with CHD, elevated homocysteine strongly predicts a poor outcome, further suggesting that it reflects the severity of CHD and possibly the risk of thrombosis.¹¹ In support of this hypothesis, recent evidence suggests that the endothelial dysfunction found after a heart attack may raise plasma homocysteine. The inconsistent results found in homocysteine studies also provide some skepticism. Seven prospective, case-control studies support homocysteines role in cardiovascular disease whereas five do not. Two of the seven positive prospective studies, however, included patients known to have preexisting coronary disease.

The extremely high, nonphysiologic doses of homocysteine used in many studies is another reason why some researchers are awaiting results of randomized, controlled trials before drawing any conclusions.

Despite the controversy, evidence still exists to support the causal link between homocysteine and disease. While it is true that a 7.5-year follow-up of the physicians study mentioned above indicated a weakening relationship between homocysteine and cardiovascular disease over time, it is also true that the physicians who experienced a cardiovascular event had baseline measurements higher than controls prior to developing their cardiovascular condition.

Another important study in Jerusalem examined 1788 residents between 1985 and 1987 with a 9-to-11 year follow-up. During the study, the 405 deaths that occurred from all causes - not just cardiovascular disease - were strongly linked to elevated homocysteine levels, even after excluding pre-existing cases of cardiovascular disease and diabetes. The one exception was cancer, which did not appear to be related to elevated homocysteine levels, a finding consistent with other studies reporting that homocysteine can actually inhibit the growth of some cancer cell lines.¹²

One concern is that elevated homocysteine might not be a risk factor in itself; rather, some have proposed that homocysteine exacerbates conventional risk factors, such as smoking or high cholesterol. One study of 750 atherosclerotic vascular disease patients and 800 controls showed that homocysteine levels were as strongly related to vascular disease as cholesterol levels and smoking. Those subjects whose homocysteine levels were in the top fifth had twice the chance of contracting vascular disease compared with the remaining four fifths. However, when adjusted for the presence of conventional risk factors the relative risks for homocysteine levels were reduced only marginally and remained independent and strong predictors of vascular disease despite interactions with other risk factors. Although homocysteine was a risk factor in and of itself, researchers also discovered that elevated fasting homocysteine level multiplied the negative effects of cholesterol, smoking and blood pressure. It is conceivable, the researchers stated, That homocysteine may augment smoking-related platelet and clotting effects or exert a toxic effect on the endothelium, and these might be more relevant to the genesis of vascular disease than reported effects of homocysteine and lipoprotein oxidation.¹³

Another argument that homocysteine precedes vascular disease revolves around vitamin intake. An association exists between folate and vitamin B6 deficiency and vascular disease. These vitamins have also been found to lower homocysteine levels. The fact that elevated homocysteine levels are common in elderly persons further supports this amino acids role in life extension.

The Role of Vitamins

Numerous studies have shown the powerful effects B vitamins have on homocysteine. In one study of 750 subjects and 800 controls, plasma homocysteine concentration dropped as blood levels of folate, cobalamin and pyridoxine rose. Users of vitamin preparations containing these nutrients appeared to experience substantial protection from vascular disease compared to nonusers.¹⁴ In most cases, including genetic, vitamin supplementation results in a near normalization of plasma homocysteine.¹⁵

The normalization evident with folate supplementation may be dose dependent. In one study of 491 adults with hypertension, dyslipidemia, and/or Type 2 diabetes, serum total homocysteine concentrations were elevated in participants consuming less than 400 mcg folate/day, but fell as folate intakes exceeded 400 mcg/day.¹⁶

The effect of B vitamins is also dependent upon the type of elevated homocysteine. A placebo-controlled study of healthy kidney transplant recipients showed that whereas fasting homocysteine can be lowered by a combination of folate and vitamin B12, post-methionine load homocysteine can only be lowered by B6 supplementation.¹⁷

Another important homocysteine-regulating nutrient is betaine, which is essential in recycling homocysteine back to methionine.¹⁸ Betaine has been shown to lower homocysteine levels in the majority of patients unresponsive to vitamin B6 therapy. In one study, daily doses of 250 mg of vitamin B6, 5 mg of folic acid, and 6 gm of betaine by themselves or in combination normalized the majority of high homocysteine levels in patients administered high doses of methionine.¹⁹

Interestingly, many researchers call for the use of vitamin supplements while waiting for more conclusive randomized trials to investigate whether homocysteine precedes disease. One group of researchers questioned whether the current recommended daily allowances of vitamins that modulate homocysteine metabolism are adequate.²⁰ Another group of scientists stated, Because vitamins are relatively inexpensive, there is little incentive on the part of drug companies to support such a trial, and it is up to government agencies to assume this task. The researchers went on to emphasize the importance of supplementing all three participants in homocysteine metabolism-folate, vitamin B12 and B6, as reduction of homocysteine levels in plasma requires all three vitamins.²¹

Recent research suggests that cardiovascular disease is only one aspect of the protective effect of B vitamins. The implications have become substantially more far-reaching as scientists have begun unearthing links between homocysteine and numerous other diseases.

Homocysteine, Rheumatoid Conditions and Chronic Fatigue

Researchers are now beginning to suspect a link between homocysteine and the high frequency of cardiovascular disease in rheumatoid arthritis patients. In one study, 38 women with rheumatoid arthritis showed significantly higher levels of total plasma homocysteine than 25, age-matched controls. Researchers have associated the rise in homocysteine with the folate antagonist drug, Methotrexateª (MTX), commonly used to treat rheumatoid arthritis patients, as MTX users experience raised homocysteine concentrations.^22-23

Folic acid supplementation has been successful at lowering the MTX-induced rise in homocysteine levels. In a double blind, controlled trial, 79 patients taking low dose MTX were given either a placebo or folic acid supplements.Over one year, the placebo group more frequently experienced declining folate levels together with hyperhomocystinemia compared to the folic acid supplemented group.²⁴

High homocysteine levels may also have an impact on fibromyalgia and chronic fatigue syndrome. In one study of 12 women diagnosed with both fibromyalgia and chronic fatigue syndrome, the cerebrospinal fluid of all the patients had increased levels of homocysteine. The researchers concluded that low vitamin B12 levels, a nutrient necessary for efficient remethylation of homocysteine, contributed to the elevated homocysteine levels.²⁵

Parkinsons Disease, Alzheimers and Dementia

Increasing evidence suggests that homocysteine is associated with cognitive impairment and Alzheimers disease. Homocysteine is, in fact, toxic to the medulloblastoma cells of the brain, one explanation why high homocysteine levels result in neural tube defects in prenatal humans, a condition that involves the same cell-type. This cell type may also be involved in the degenerative processes of Alzheimers and Parkinsons.²⁶ Oxidation products of homocysteine are excitatory sulfur amino acids and may act as excitatory neurotransmitters. During folate, cobalamin or pyridoxine deficiency, the profile of these sulfur amino acid neurotransmitters could be altered, possibly resulting in homocysteine-induced catabolism in the brain.²⁷

The link between elevated homocysteine levels and psychiatric conditions was supported by recent research. In one study of 741 psychogeriatric-demented and non-demented patients with other psychiatric disorders, plasma homocysteine concentrations were significantly increased in both the demented and the non-demented patients, but only the demented patients had significantly lower blood folate concentrations than 163 control subjects.²⁸ In Parkinsons patients, raised homocysteine levels have been attributed to the drug levodopa. Researchers have associated elevated homocysteine levels commonly found in Parkinsons patients with an increased risk of vascular disease.²⁹

Pregnancy-induced Hypertension and Miscarriages

In women with recurrent miscarriages or those who had given birth to an infant with a neural tube defect, the remethylation of homocysteine to methionine is likely to be disturbed because of a decreased activity of one of the involved remethylation enzymes and/or folate or Vitamin B12 deficiencies. In addition, ovarian follicular fluid contains detectable amounts of homocysteine along with B12, B6, and folate. Because follicular fluid provides nourishment to the oocyte by facilitating transport from plasma, the ovum may be exposed to high homocysteine or low methionine concentrations or both, as well as a lack of vitamins. The vitamins fed to the ovum through this route, as well as the balance of homocysteine to methionine, may be important to fertilization and early embryogenesis.³⁰

Pre-eclampsia, a complication of pregnancy characterized by increasing hypertension and edema, can lead to eclampsia if left untreated, a leading cause of fetal and maternal morbidity and death. In late gestation, levels of homocysteine are higher in preeclamptics as compared to pregnant women with normal blood pressure. In one study, a second trimester elevation of homocysteine was associated with a 3.2 fold increased risk of pre-eclampsia.³¹

Other Reasons for Elevated Homocysteine

Medications such as Azaribine (a vitamin B6 antagonist); phenytoin (Dilantin) and carbamazepine (Tegretol) (anticonvulsants that interfere with folate metabolism); and the administration of nitrous oxide in anesthesia during operations all have been shown to raise homocysteine levels. Homocysteine is also elevated in hypothyroidism, a disease possibly associated with an increased risk for coronary artery disease and lower levels of folate.³²

Conclusion

Even if homocysteine is merely a consequence of disease, elevated levels could be as deadly as if it were the initial cause behind the condition. The ability to increase survival rates in renal failure patients by reducing their homocysteine levels demonstrates that taking action against high levels of this amino acid can have important consequences in life-extension.According to one group of researchers, “If the association between elevated plasma homocysteine level and mortality is even partly causal, the benefit from a simple intervention, such as folate fortification or supplementation, could be large.”³³

Supplementation with Advanced Methyl Caps, a synergistic blend that contains homocysteine-lowering folate and vitamins B6 and B12 combined with betaine, would seem to be a logical choice for controlling high homocysteine.

References

1. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA. 1995; 274:1049-57.

2. Swift ME, Schultz TD. Relationship of vitamins B6 and B12 to homocysteine levels: risk for coronary heart disease. Nutr Rep Int. 1986; 34:1-14.

3. Selhub J, Miller JW. The pathogenesis of homocyst(e)inemia: interruption of the coordinate regulation by S-adenosylmethionine of the remethylation and transsulfuration of homocysteine. Am J Clin Nutr. 1991; 55:131-38.

4. Miller JW, Nadeau MR, Smith D, Selhub J. Vitamin B6 deficiency vs folate deficiency: comparison of responses to methionine loading in rats. Am J Clin Nutr. 1994; 59:1033-39.

5. Miller JW, Ribaya-Mercado JD, Russell RM, Shepard DC, Morrow FD, et al. Total homocysteine in fasting plasma is not a good indicator of B6 deficiency. Am J Clin Nutr. 1992; 55:1154-60.

6. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA. 1995; 274:1049-57.

7. Refsum H, Ueland PM, Nygard O, Vollset SE. Homocysteine and cardiovascular disease. Annu Rev Med. 1998; 49:31-62.

8. Nygard O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SE. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med. 1997; 337:230-36.

9. Stampfer MJ, Malinow MR, Willett WC, et al. A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. JAMA. 1992;268:877-81.

10. Meleady R, Graham I. Plasma homocysteine as a cardiovascular risk factor: causal, consequential or of no consequence? Nutr Rev. 1999; 57(10):299-305.

11. Nygard O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SM. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med. 1997; 337:230-36.

12. Kark JD, Selhub J, Adler B, Gofin J, Abramson JH, Friedman G, Rosenberg IH. Nonfasting plasma total homocysteine level and mortality in middle-aged and elderly men and women in Jerusalem. Ann Intern Med. 1999; 131(5): 321-30.

13. Graham IM, Daly LE, Refsum HM, Robinson K, Brattstrom LE, Ueland PM, Palma-Reis RJ, et al. Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project. JAMA. 1997; 277(22):1775-81.

14. Graham IM, Daly LE, Refsum HM, Robinson K, Brattstrom LE, Ueland PM, Palma-Reis RJ, et al. Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project. JAMA. 1997; 277(22):1775-81.

15. Ubbink JB, Vermaak WJH, van der Merwe A, Becker PJ, Delport R, Potgieter HC. Vitamin requirements for the treatment of hyperhomocystinemia in humans. J Nutr. 1994; 124:1927-33.

16. Chait A, Malinow MR, Nevin DN, Morris CD, Eastgard RL, Kris-Etherton P, Pi-Sunyer FX, Oparil S, Resnick LM, et al. Increased dietary micronutrients decrease serum homocysteine concentrations in patients at high risk of cardiovascular disease. Am J Clin Nutr. 1999; 70(5):881-7.

17 Selhub J. Homocysteine metabolism. Annu Rev Nutr. 1999; 19:217-46.

18. Betaine for Homocystinuria. The Medical Letter. 1997; 39(993):12.

19. Boers GHJ. Hyperhomocystinemia: A Newly Recognized Risk Factor For Vascular Disease. Netherlands Journal of Medicine. 1994; 45:34-41.

20. Chait A, Malinow MR, Nevin DN, Morris CD, Eastgard RL, Kris-Etherton P, Pi-Sunyer FX, Oparil S, Resnick LM, et al. Increased dietary micronutrients decrease serum homocysteine concentrations in patients at high risk of cardiovascular disease. Am J Clin Nutr. 1999; 70(5):881-7.

21. Selhub J. Homocysteine metabolism. Annu Rev Nutr. 1999; 19:217-46.

22. Hernanz A, Plaza A, Martin-Mola E, De Miguel E. Increased plasma levels of homocysteine and other thiol compounds in rheumatoid arthritis women. Clin Biochem. 1999; 32(1):65-70.

23. Haagsma CJ, Blom HJ, van Riel PL, vant Hof MA, Giesendorf BA, et al. Influence of sulphasalazine, methotrexate, and the combination of both on plasma homocysteine concentrations in patients with rheumatoid arthritis. Ann Rheum Dis. 1999; 58(2):79-84.

24. Morgan SL, Baggott JE, Lee JY, Alarcon GS. Folic acid supplementation prevents deficient blood folate levels and hyperhomocystinemia during long term, low dose methotrexate therapy for rheumatoid arthritis: implications for cardiovascular disease prevention. J Rheumatol. 1998; 25(3):441-6.

25. Regland B, Andersson M, Abrahamsson L, Bagby J, Dyrehag LE, Gottfries CG. Increased concentrations of homocysteine in the cerebrospinal fluid in patients with fibromyalgia and chronic fatigue syndrome. Scand J Rheumatol. 1997; 26(4):301-7.

26. Parsons RB, Waring RH, Ramsden DB, Williams AC. In vitro effect of the cysteine metabolites homocysteic acid, homocysteine and cysteic acid upon human neuronal

Kolhouse JF. Are neuropsychiatric manifestations of folate, cobalamin and pyridoxine deficiency mediated through imbalances in excitatory sulfur amino acids? Med Hypotheses. 1994; 43(4):239-44.

28. Nilsson K, Gustafson L, Faldt R, Andersson A, Brattstrom L, Lindgren A, Israelsson B, Hultberg B. Hyperhomocysteinaemia-a common finding in a psychogeriatric population. Eur J Clin Invest. 1996; 26(10):853-9.

29. Muller T, Werne B, Fowler B, Kuhn W. Nigral endothelial dysfunction, homocysteine, and Parksinson’s disease. Lancet. 1999; 354(9173):126-7.

30. Steegers-Theunissen RP, Steegers EA, Thomas CM, Hollanders HM, et al. Study on the presence of homocysteine in ovarian follicular fluid. Fertil Steril. 1993; 60(6):1006-10.

31. Sorensen TK, Malinow MR, Williams MA, King IB, Luthy DA. Elevated second-trimester serum homocyst(e) ine levels and subsequent risk of preeclampsia. Gynecol Obstet Invest. 1999; 48(2):98-103.

32. Catargi B, Parrot-Roulaud F, Cochet C, Ducassou D, Roger P, Tabarin A. Homocysteine, hypothyroidism, and effect of thyroid hormone replacement. Thyroid. 1999; 9(12):1163-6.

33. Kark JD, Selhub J, Adler B, Gofin J, Abramson JH, Friedman G, Rosenberg IH. Nonfasting plasma total homocysteine level and mortality in middle-aged and elderly men and women in Jerusalem. Ann Intern Med. 1999; 131(5): 321-30.

Vitamin B12 Important for Cognitive Health

Scientists have discovered that vitamin B12 may protect against the brain volume loss that occurs in the elderly, which could reduce the risk of dementia.

Previously, low levels of vitamin B12 and other B vitamins have been linked with higher levels of homocysteine, an amino acid thought to increase the risk of dementia or cognitive dysfunction.

Researchers from the University of Oxford studied 107 community-dwelling subjects between the ages of 61 and 87 who did not suffer from cognitive impairment at the study’s start.

The study authors collected blood samples to measure levels of vitamin B12 as well as total homocysteine and folate. None of the volunteers were deficient in vitamin B12. Brain volume loss per year was calculated using MRI scans.

During the five-year study, the researchers noted a greater decrease in brain volume among people with the lowest levels of vitamin B12 (below 308 picomoles per liter). Subjects with lower B12 levels were six times more likely to experience brain shrinkage. High levels of homocysteine were not linked to brain volume loss, indicating that vitamin B12’s effect on the brain was independent of its effect on homocysteine. Low folate levels also were not associated with brain volume loss.

The researchers concluded, “Low vitamin B(12) status should be further investigated as a modifiable cause of brain atrophy and of likely subsequent cognitive impairment in the elderly.”

Reference:

Vogiatzoglou A, Refsum H, Johnston C, Smith SM, Bradley KM, de Jager C, Budge MM, Smith AD. Vitamin B12 status and rate of brain volume loss in communitydwelling elderly. Neurology. 2008 Sep 9;71(11):826-32.

The vitamin B12 available here is the active, functional form known as methylcobalamin, and uses a sublingual delivery for better utilization. Most B12 vitamin supplements are cyanocobalamin and rely on conversion for use. Aging and use of acid blockers increase the risk of lower than optimal levels of B12.

Low Vitamin E Levels Associated with Kidney Stones in Animal Study

Low levels of vitamin E are linked to an increased risk of kidney stones, a new animal study reveals.

To determine whether low vitamin E levels cause oxidative stress in the kidneys and accelerate the formation of kidney stones, researchers fed rats a number of different diets. The control group received a standard diet and drinking water, while the experimental groups received 0.75 percent ethylene glycol, a substance that causes kidney stones, in drinking water for 42 days. Of the rats receiving the ethylene glycol, one group received a standard diet, one group received a low-vitamin-E diet, and the last group received a low-vitamin- E diet with a vitamin E supplement.

In rats given only the ethylene glycol, kidney stone accumulation was associated with alterations in antioxidant activity. In rats given the ethylene glycol and fed a lowvitamin-E diet, there were marked changes in antioxidant and oxidative enzyme levels, and these changes correlated with massive deposition of the crystal deposits that cause kidney stones as well as tubular damage. However, the increased oxidative stress seen in the rodents on a low-vitamin-E diet was largely reversed by vitamin E supplementation.

In a separate experiment, rats given ethylene glycol and ethylene glycol plus a low-vitamin-E diet were studied on days 3-42 to examine the relationship between oxidative change and kidney stone formation. In ethylene-glycol-treated rats, kidney stone accumulation was associated with altered antioxidant enzyme activity. In the animals given both ethylene glycol and a low-vitamin-E diet, the changes that occurred in antioxidant and oxidative enzyme levels correlated with massive kidney stone deposition and tubular damage. The increased oxidative stress seen in animals treated with ethylene glycol and fed a low-vitamin-E diet was largely reversed by vitamin E supplementation. The researchers noted that because the decrease in antioxidant defense and increase in free radical formation occurred in the low-vitamin-E group before kidney stone crystal deposition, there appears to be an association between alterations in antioxidant activity in the kidney and formation of kidney stones.

According to the researchers, “This study shows that LE [low vitamin E] disrupts the redox balance and causes cell death, thereby favoring crystal formation.”

Reference:

Huang HS, Ma MC, Chen J. Low Vitamin E Diet Exacerbates Calcium Oxalate Crystal Formation Via Enhanced Oxidative Stress in Rat Hyperoxaluric Kidney. Am J Physiol Renal Physiol. 2008 Sep 17. Published online ahead of print.

Turmeric Component Acts as Natural Antidepressant in Animal Study

A new animal study indicates that the turmeric-derived component curcumin may act as a natural antidepressant.

Mice were subjected to a forced swim test, which is used as an animal model of depression because the length of time the rodents swim before giving up is an indication of the animal’s mental state. Biochemical and neurochemical indicators of mood in the animals (monoamine oxidase-MAO-enzyme inhibitory activity and neurotransmitter levels estimation) were also measured.

Curcumin dose dependently inhibited the immobility period, increased serotonin as well as dopamine levels and inhibited the monoamine oxidase enzymes (both MAO-A and MAO-B) in the mice. Curcumin also enhanced the antidepressant effect of antidepressant drugs. Furthermore, a combination of curcumin and various antidepressant drugs resulted in synergistic increase in serotonin levels.

According to the researchers, “The study provides evidences for mechanism-based antidepressant actions of curcumin.”

Reference:

Kulkarni SK, Bhutani MK, Bishnoi M. Antidepressant activity of curcumin: involvement of serotonin and dopamine system. Psychopharmacology (Berl). 2008 Sep 3. Published Online Ahead of Print.

Omega-3s May Protect The Heart Against Pollution

Researchers have discovered that supplementing with omega-3 fatty acids may protect the heart against exposure to air pollution.

Exposure to high levels of particulate matter (PM) from vehicle exhaust and industrial pollution is known to damage the heart, due to increased inflammation and oxidative stress. Small particulate matter less than 2.5 micrometres – PM(2.5) may also reduce the protective actions of antioxidant enzymes in the body, such as copper/zinc (Cu/Zn) superoxide dismutase (SOD), manganese SOD, and glutathione peroxidase (GSH-Px). Increased intake of omega-3 polyunsaturated fatty acids appears to have anti-inflammatory effects. Therefore, researchers conducted a trial to determine whether omega-3 fatty acids could protect against the cardiac alterations linked to particulate matter exposure.

Researchers recruited residents from a nursing home in Mexico City who were chronically exposed to small particulate matter PM(2.5) or less and randomly assigned the subjects in a double-blind fashion to receive either fish oil (n-3 PUFA) or soy oil. The researchers then followed them for nearly seven months.

The study authors measured PM(2.5) levels indoors at the nursing home and measured levels of antioxidant enzymes at different times during pre-supplementation and supplementation phases.

Supplementation with either fish or soy oil was related to an increase in activity of the antioxidant enzyme Cu/Zn SOD and an increase in plasma levels of the antioxidant gluathione.

The omega-3s exerted a much greater protective effect compared to the soy oil. The researchers thought this difference was likely due to the fact fish oil contains EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), while soy oil contains ALA (alpha-linolenic acid).

T h e r e s e a r c h e r s c o n c lu d e d , “Supplementation with n-3 PUFA appeared to modulate the adverse effects of PM(2.5) on these [antioxidant enzyme] biomarkers, particularly in the fish oil group. Supplementation with n-3 PUFA could modulate oxidative response to PM(2.5) exposure.”

Reference:

Romieu I, Garcia-Esteban R, Sunyer J, Rios C, Alcaraz-Zubeldia M, Velasco SR, Holguin F. The effect of supplementation with omega-3 polyunsaturated fatty acids on markers of oxidative stress in elderly exposed to PM(2.5). Environ Health Perspect. 2008 Sep;116(9):1237-42.

Vitamin D Linked to Enhanced Breast Health

Researchers report that vitamin D may reduce the risk of breast cancer and inhibit both estrogen-receptor positive and progesterone-receptor positive tumors.

Hormone-sensitive estrogen-receptor positive and progesterone-receptor positive tumors are thought to be the most common type diagnosed among breast cancer patients in the US. A tumor is said to be estrogen-receptor positive if its growth is stimulated by estrogen and progesteronereceptor positive if its growth is stimulated by progesterone. Past studies have suggested that vitamin D’s antiproliferative effect is greater in hormone-receptor-positive cells, but few epidemiologic studies have considered this association between vitamin D and hormone-receptor-defined breast cancer.

In the new study, researchers compared 759 women with breast cancer and 1,135 controls without breast cancer. The scientists examined the association between vitamin D intake at specific ages and incidence of combined estrogen-receptor and progesterone-receptor defined breast cancer. The results indicated that subjects with the highest levels of vitamin D from the sun and diet had a significant 24 percent reduction in the risk of estrogen-receptor positive and progesterone-receptor positive tumors.

Subjects with higher intakes of vitamin D also had a 26 percent reduction in the risk of receptor-negative tumors and a 21 percent reduction in the risk of mixed receptor tumors. However, these last two associations were non-significant.

The researchers concluded, “This study suggests that vitamin D is associated with a reduced risk of breast cancer regardless of ER/PR status of the tumor. Future studies with a larger number of receptor-negative and mixed tumors are required.”

Reference:

Blackmore KM, Lesosky M, Barnett H, Raboud JM, Vieth R, Knight JA. Vitamin D From Dietary Intake and Sunlight Exposure and the Risk of Hormone-Receptor-Defined Breast Cancer. Am J Epidemiol. 2008 Aug 27.

Glucosamine/Chondroitin Improves Joint Pain and Cartilage Damage in Animal Model of Arthritis

According to a new study, glucosamine sulfate combined with chondroitin sulfate reduced joint pain and cartilage damage in an animal model of osteoarthritis.

Researchers induced osteoarthritis in rats. They then gave the rodents either glucosamine alone, glucosamine plus chondroitin or a placebo starting 7 days prior to when the osteoarthritis was induced until 70 days into the study, when the rodents were sacrificed. Joint pain was evaluated daily using the rat-knee joint articular incapacitation test. Structural joint damage also was assessed.

The combination of glucosamine and chondroitin—but not glucosamine alone—significantly reduced joint pain compared to the controls. There was an increase in chondroitin content in the osteoarthritis group given the two nutrients compared to controls. The structural changes that occurred in the cartilage of rats with experimental osteoarthritis also were significantly prevented by administration of both the glucosamine and chondroitin.

The researchers concluded that glucosamine sulfate plus chondroitin sulfate provides analgesic and structural benefits in this animal model of arthritis. They noted that this was the first study to show that the biochemical alterations that occur along with structural damage in osteoarthritis are prevented by glucosamine/chondroitin administration.

Reference:

Silva FS Jr, Yoshinari NH, Castro RR, Girão VC, Pompeu MM, de Andrade Feitosa JP, Rocha FA. Combined glucosamine and chondroitin sulfate provides functional and structural benefit in the anterior cruciate ligament transection model. Clin Rheumatol. 2008 Sep 13. Published online ahead of print.

EpiCor® Increases Volume of Red Blood Cells and Boosts Immunity

Scientists have found that daily supplementation with EpiCor® improved immune function, reduced inflammation and increased the volume of red blood cells in human subjects.

The scientists enrolled 25 healthy participants with an average age of 27.6 and randomly assigned them to receive daily EpiCor supplements (500 mg) or a placebo for five weeks. Among subjects taking EpiCor, there was an approximate 7 percent increase in volume of red blood cells (hematocrit). Moreover, the content of hemoglobin increased in red blood cells after EpiCor consumption compared to baseline, while the number of red blood cells did not increase. No significant change in red blood cells was observed in the placebo group. This increase in volume of red blood cells indicated that the RBCs being produced were healthier after EpiCor consumption, the researchers explained.

The researchers also noted that subjects consuming EpiCor experienced a mild increase in saliva levels of secretory IgA (sIgA), an antibody that coats the mucous membranes, thereby protecting against viral and bacterial invaders. The researchers followed up this sIgA aspect of the study with another subsequent 8-week trial. In this study of 22 subjects, there was a statistically significant increase in sIgA in participants given EpiCor.

Furthermore, an increase in levels of the anti-inflammatory cytokine interleukin-10 (IL-10) occurred after EpiCor use. The researchers noted other results, including the fact that seasonal allergies increased in the placebo group, but were not observed in the EpiCor group.

Reference:

Jensen GS, Patterson KM, Barnes J, Schauss AG, Beaman R, Reeves SG, Robinson LE. A Double-Blind Placebo-Controlled, Randomized Pilot Study: Consumption of a High-Metabolite Immunogen from Yeast Culture has Beneficial Effects on Erythrocyte Health and Mucosal Immune Protection in Healthy Subjects. The Open Nutrition Journal. 2008;2;68-75.

The EpiCor available here is 100 percent pure EpiCor. Our product contains no fillers or flow agents.

LGG May Inhibit Mutagenic Processes, Improve Heart Health and Decrease Bowel Inflammation

Researchers have found that the probiotic Lactobacillus rhamnosus GG (LGG) decreases levels of lipids involved in detrimental processes such as angiogenesis (the formation of new blood vessels that can feed cancer cells), inflammation related to hardening of the arteries, cancer development, oxidative stress and inflammatory bowel disease.

For the three-week, randomized, double-blind, placebo-controlled trial, the researchers recruited 26 healthy people average age 42 (14 of them women). Subjects received either LGG supplements or a placebo.

In what was the first study to investigate the effects of probiotic intervention on lipid profiles in humans, researchers measured the subjects’ lipid profiles by analyzing blood samples. The researchers identified 407 lipids.

The results indicated that supplementation with the probiotic was associated with decreases in lipids known as LysoGPCho (lysophosphatidylcholines) and sphingomyelins (SM).

LysoGPCho is reported to be involved in destructive processes such as oxidative metabolism, angiogenesis, and carcinogenesis. It is thought to be a pro-inflammatory lipid, and LGG’s effects on LysoGPCho may account for the fact that supplementation with the probiotic reduced compounds associated with inflammation, especially interleukin-6 (IL-6). LysoGPCho also is a major heart-disease-promoting lipid formed from oxidized LDL (“bad cholesterol”), and it has been associated with vascular inflammation, endothelial dysfunction and coronary atherosclerosis.

The lipid SM also has been connected to inflammation that plays a role in atherosclerosis as well as other inflammatory processes that may cause inflammatory bowel disease. LGG’s ability to reduce levels of SM may indicate it has a role to play in these conditions and may explain why past studies have shown the probiotic can support the health of patients with inflammatory bowel disease.

Reference:

Kekkonen RA, Sysi-Aho M, Seppanen-Laakso T, Julkunen I, Vapaatalo H, Oresic M, Korpela R. Effect of probiotic Lactobacillus rhamnosus GG intervention on global serum lipidomic profiles in healthy adults. World J Gastroenterol. 2008;14(20):3188-94.

Lactobacillus rhamnosus GG (LGG) is found in Culturelle®.

Bilberry Plays Role in Liver Health

By virtue of strong antioxidant abilities, bilberry may protect the health of the liver, an animal study suggests.

In rodents, scientists induced serious liver damage, which was marked by an increase in plasma alanine aminotransferase (ALT) levels. ALT levels are used as a measurement of liver health. The liver damage also was characterized by increased levels of a marker of oxidative stress known as malondialdehyde (MDA) as well as lowered levels of oxygen radical absorbance capacity (ORAC) values in the plasma and livers of the animals.

When bilberry extract was orally administrated to the mice for five days, there was a remarkable decrease in the plasma ALT level. In addition, bilberry extracts increased glutathione and vitamin C levels and significantly decreased levels of the oxidative marker MDA in the liver tissues. Bilberry was able to inhibit lipid oxidation, the process where lipids undergo oxidative damage caused by free radicals.

The study authors concluded that bilberry extract plays an important role in protecting against liver damage by “both scavenging free radicals activity and an lipid peroxidation inhibitory effect. This study showed the beneficial health effects of bilberry extract through its antioxidative action.”

Reference:

Bao L, Yao XS, Yau CC, Tsi D, Chia CS, Nagai H, Kurihara H. Protective effects of bilberry (Vaccinium myrtillus L.) extract on restraint stress-induced liver damage in mice. J Agric Food Chem. 2008 Sep 10;56(17):7803-7.