• The President’s Desk  — Serving Our Customers, Med Schools Fail Test

• Active Folate  — New More Bioavailable Form Addresses A Common Nutrient Deficiency

• Sleep Loss  — Is it Linked to a Number of Common Diseases?

• Allergic Rhinitis  — A Spring Survival Guide for Allergy Sufferers

• Stress Relief  — Strengthening the Body’s Defenses and Enhancing Peace of Mind

• Pet Corner  — Inflammatory Bowel Disease in Pets

• Nutrition Review  — Latest Research on Depression, Blood Pressure, Colon Health and More

• Porangaba Tea:  — Powerful Weight Loss Aid

• Weight Loss and Endothelial Dysfunction  — Only 9 Pounds of Weight Gain in Lean Adults Increases Heart Disease Risk

• Chronic Fatigue
• Xylitol for Gum Health
• Atrial Fibrillation in Young Man
• Sciatic Nerve Pain
• Sinus Health
• Post-Prostatectomy Support
• Baker's Cyst
• Neurotoxin Overload
• Thyroid Health, Gallstones, Acne
• GERD, Barrett's Esophagus
• Supplements for Marathoner

By the time you receive this newsletter, VRP will be operating with our new integrated software package! As we implement this system, a few issues may arise. I apologize for any frustrations you may experience. In the long run, this will allow us to better serve you, our customers.

I want to thank those of you who share with us your experiences with our company. It means a lot to us that in this busy world you take the time to provide us with input. As an employee-owned company, it’s very important that we stay connected to you as we realize we’re in the business to service your needs. While it may be difficult to get back to everyone immediately, rest assured we read every comment we receive.

In other news, the American Medical Student Association released its report card ranking medical schools by how well these institutions monitor and control drug industry money and perks. The results suggest that many professors are on the dole for the drug companies and their schools aren’t doing much about it. For example, Harvard Medical School received a failing grade because it either has no policy or implements policies that don’t have a substantial effect on how faculty interacts with Big Pharma, including accepting gifts and meals, providing consulting to the drug companies and participating in industry-funded speaking relationships. Other medical schools to receive a failing grade include Louisiana State University, University of Florida, and Tulane University. Of the more than 150 schools evaluated, 43 received a failing grade, 27 received a D, and 8 schools received a C. Although a number of schools did receive an A or B, there is still a lot of room for improvement. With such conflicts of interests occurring in medical school, is it any wonder conventional medicine often shuns nutritional supplements in favor of pharmaceutical drugs?

The human body can generally convert basic forms of nutrients into their biological active forms, yet there are times where the process of conversion is either faulty or incapable of optimally performing this health-sustaining transformation. 5-MTHF, often abbreviated MTHF, is the most biologically active form of folate and is the molecule to which folic acid must be converted in the body to be utilized.

MTHF functions with methylcobalamin (vitamin B12), as a methyl-group donor involved in the conversion of the amino acid homocysteine to methionine. The importance of methyl (CH3) group donation cannot be over-emphasized, as it is involved in countless processes, including serotonin, melatonin, and DNA synthesis. In the case of 5-MTHF there are specific applications relative to sustaining wellness including controlling the level of homocysteine (an amino acid linked to heart disease), preventing neural tube defects, and improving vascular endothelial function. Endothelial cells are the cells that line the blood vessels. When there is damage to the endothelium—the blood vessel lining that contains these cells—it can obstruct blood flow, leading to heart attacks and strokes.

There is significant evidence that sufficient levels of folic acid, also known as folate, are involved in helping with not only the health aspects mentioned above but also countless number of other conditions (See Table 1).

The synthesis of the active forms of folic acid requires several enzymes, adequate liver and intestinal function, and adequate supplies of riboflavin (B2), niacin (B3), pyridoxine (B6), zinc, vitamin C, and serine. Even with the assumption that all these nutrients are present in sufficient amounts to allow for the conversion of dietary or supplemental folic acid to the bioactive form, there is still another confounding variable that can still compromise optimal MTHF generation within the body. These variables include enzyme defects, malabsorption, digestive system pathology, and liver disease.

Individuals with methylenetetrahydrofolate reductase (5-MTHFR enzyme) defects will have varying inability to convert folic acid to 5-MTHF.^1-5

Folic Acid’s Most Active Form

There is evidence pointing to the benefits of using the biologically active form of folic acid, MTHF, as a preferred supplement form. Significantly greater red blood cell folate concentrations were observed after 24 weeks of supplementation with 5-MTHF compared to folic acid and placebo.⁶

A single, high-dose pharmacokinetic study of 5-MTHF or folic acid administration (5 mg) in patients with coronary artery disease demonstrated significantly higher bioavailability of 5-MTHF, which resulted in a 700-percent higher plasma folate concentration after 5-MTHF dosing compared to folic acid. This difference was irrespective of the patient’s enzymatic genotype.⁷

Folic Acid Deficiency and Symptoms

Folic acid deficiency is believed to be one of the most common nutritional deficiencies, which should not be surprising with statistics reporting that only 11 percent consume the daily recommendation of 5 to 7 servings of vegetables and fruit. Common presentations of insufficient folic acid can include macrocytic anemia (too large of red blood cells), fatigue, irritability, peripheral neuropathy, tendon hyper-reflexivity, restless legs syndrome, diarrhea, weight loss, insomnia, depression, dementia, and psychiatric conditions.^8-13

Anemia

While having ones annual blood work done, getting a CBC (Complete Blood Count with Differential) is very important.  The MCV result on this test combined with total red blood cell count provides insight as to potential nutrient deficiencies.  When red blood cells are enlarged, called macrocytic, the use of both folic acid with vitamin B12 is the most common treatment approach by nutritional minded healthcare providers. Depending on the patient’s nutritional status, the dose of folic acid or 5-MTHF required to reverse macrocytic anemia varies, but the therapeutic dose is usually 800-1,000 mcg (1 mg) daily.

Elevated Homocysteine

Elevated plasma homocysteine is an independent risk factor for cardiovascular disease. Hyperhomocysteinemia has been connected to increased risk of neural tube defects, Alzheimer’s disease, cognitive decline, osteoporosis, rheumatoid arthritis, kidney failure, and cancer.^14-15

MTHF is required for optimal homocysteine metabolism, since it acts as a methyl donor, thus providing a methyl group to vitamin B12. The methylated form of vitamin B12 (methylcobalamin) is the active form of B12 and can transfer its methyl group to homocysteine. Sufficient presence of methyl donors is absolutely essential for the re-transformation of homocysteine to methionine, resulting in homocysteine reduction.

Cardiovascular Disease

MTHF can assist in lowering homocysteine and also enhance blood flow by increasing nitric oxide (NO) production in vascular endothelial cells. Impaired endothelial NO production arises as part of the pathological changes of cardiovascular disease, particularly atherosclerosis. The risk of atherosclerosis is amplified significantly as a result of the associated poor vasodilation due to insufficient nitric oxide production.

Homocysteine compromises the ability to generate sufficient amounts of NO that leads to injury of the endothelial lining and propagates further atherosclerosis. The pathophysiology that manifests includes increased “stickiness” of monocytes and platelets, increased smooth muscle proliferation, and clot formation. The evidence suggests that MTHF can improve NO synthesis by lowering homocysteine levels, while helping mitigate the impairment of dysfunctional endothelial NO production.  MTHF also appears to reduce free radical generation and can substitute for tetrahydrobiopterin as a cofactor in the enzyme nitric oxide synthase, with an cumulative effect of improvement of blood flow.^16-21

Inflammatory Bowel Disease

Individuals with inflammatory bowel disease (IBD) will often present with folic acid insufficiency arising from the increased demand of cellular healing, malabsorption and the use of medications such as Sulfasalazine, well known to inhibit folate absorption.²² A study of 99 UC patient records found folic acid supplementation was associated with a 62-percent decreased risk of neoplasia compared to patients not taking a folate supplement.²³

Psychological Health

Several studies have documented improvement in depression in some patients subsequent to oral supplementation with 5-MTHF at doses upwards of 15-50 mg daily.^24-26 Folic acid has also been shown in some studies to significantly improve the antidepressant action of fluoxetine in subjects with major depression.²⁷ Preliminary evidence suggests that supplemental folic acid might positively affect morbidity of some bipolar patients placed on lithium therapy.²⁸

Cervical Dysplasia

There is growing evidence that there is an association between folic acid sufficiency and cervical dysplasia.^29-32 One study points to the possibility of folic acid supplementation at a dosage of 10 mg daily for three months may reverse cervical dysplasia in women taking oral contraceptives.³³

It is important to note there are reports of women infected with certain strains of human papilloma virus who do not respond to folic acid therapy. This may be suggestive that without addressing the underlying viral infection and propagation of disease it negates some of the folic acid benefits. As reflected by the positive oral contraceptive study described above, folic acid sufficiency that can become reduced with oral contraceptive use may increase susceptibility to viral infection.

Periodontal Disease

Folic acid sufficiency can improve gingival (gum) resistance to irritation and resultant inflammation and infection. A mouth rinse of folic acid used twice daily for four weeks, with a rinsing time of one minute, appears to be the most effective manner of application.^34-36 Clinically, many patients will open up 2 to 5 capsules and mix the contents with about 1 to 2 ounces of water and make their own mouth rinse for each mouth rinsing session.

Vitiligo

Folic acid is often added to vitiligo protocols. The scientific literature report varying degrees of effectiveness of re-pigmentation ranging from complete re-pigmentation in six subjects and 80-percent re-pigmentation in two subjects in eight individuals participating in a three year protocol with a dosage of 2 mg folic acid twice daily, 500 mg vitamin C twice daily, and intramuscular injections of vitamin B12 every two weeks.³⁷ Another study that spanned two-years used a combination of folic acid, vitamin B12, and sun exposure for treatment of vitiligo reported positive results. One hundred patients with vitiligo were treated, with re-pigmentation occurring in 52 subjects. Total re-pigmentation was seen in six patients and the spread of vitiligo was halted in 64 percent of the patients.³⁸

Drug Depletion

Individuals taking prescription medications should ask their pharmacist and physician about potential folic acid depletion. There are dozens of medications that can contribute to folic acid insufficiency. The list is far too lengthy for inclusion in this article. Yet, allow me to point out a couple important categories. Antacids and acid blockers can decrease the absorption of many nutrients including folic acid absorption.³⁹ Sulfasalazine interferes with folic acid absorption and conversion to 5-MTHF.⁴⁰ Long-term use of acetaminophen, aspirin, ibuprofen and other non-steroidal anti-inflammatory drugs  (NSAIDS) can apparently increase the need for enhanced intake of folate to sustain sufficiency.⁴¹

New Active Folate

The new supplement Active Folate contains 800 mcg of MTHF, which is nearly 7 times more bioavailable than ordinary folic acid. Active Folate requires no metabolic conversion before being absorbed or entering the cell. It readily crosses the blood-brain barrier and will not mask Vitamin B12 deficiency.

Conclusion

This brief review of the benefits of folic acid reflects the diverse biochemical importance of this often ignored B vitamin.  Furthermore, a meaningful percentage of the populace is unable to sustain sufficient levels of folic acid, let alone the biologically active form, MTHF. Gastrointestinal, cervical, mental, red blood cell, DNA and cellular health are all dependent upon maintaining optimal levels.

References

1. Yates JR, Ferguson-Smith MA, Shenkin A, et al. Is disordered folate metabolism the basis for the genetic predisposition to neural tube defects? Clin Genet. 1987;31:279-287.

2. Lussier-Cacan S, Xhignesse M, Piolot A, et al. Plasma total homocysteine in healthy subjects: sex specific relation with biological traits. Am J Clin Nutr. 1996;64:587-593.

3. Kluijtmans LA, Van den Heuvel LP, Boers GH, et al. Molecular genetic analysis in mild hyperhomocysteinemia: a common mutation in the methylenetetrahydrofolate reductase gene is a genetic risk factor for cardiovascular disease. Am J Hum Genet. 1996;58:35-41.

4. Whitehead AS, Gallagher P, Mills JL, et al. A genetic defect in 5,10 methylenetetrahydrofolate reductase in neural tube defects. QJM. 1995;88:763-766.

5. Ulvik A, Evensen ET, Lien EA, et al. Smoking, folate and methylenetetrahydrofolate reductase status as interactive determinants of adenomatous and hyperplastic polyps of colorectum. Am J Med Genet. 2001;101:246-254.

6. Lamers Y, Prinz-Langenohl R, Bramswig S, Pietrzik K. Red blood cell folate concentrations increase more after supplementation with [6S]-5-methyltetrahydrofolate than with folic acid in women of childbearing age. Am J Clin Nutr. 2006;84:156-161.

7. Willems FF, Boers GH, Blom HJ, et al.Pharmacokinetic study on the utilisation of 5- methyltetrahydrofolate and folic acid in patientswith coronary artery disease. Br J Pharmacol. 2004;141:825-830.

8. Pentieva K, McNulty H, Reichert R, et al. The short-term bioavailabilities of [6S]-5-methyltetrahydrofolate and folic acid are equivalent in men. J Nutr. 2004;134:580-585.

9. Venn BJ, Green TJ, Moser R, et al. Increases in blood folate indices are similar in women of childbearing age supplemented with [6S]-5-methyltetrahydrofolate and folic acid. J Nutr. 2002;132:3353-3355.

10. Houghton LA, Sherwood KL, Pawlosky R, et al. [6S]-5-methyltetrahydrofolate is at least as effective as folic acid in preventing a decline in blood folate concentrations during lactation. Am J Clin Nutr. 2006;83:842-850.

11. Halsted CH. The intestinal absorption of dietary folates in health and disease. J Am Coll Nutr. 1989;8:650-658.

12. Revell P, O’Doherty MJ, Tang A, Savidge GF. Folic acid absorption in patients infected with the human immunodeficiency virus. J Intern Med. 1991;230:227-231.

13. Botez MI. Folate deficiency and neurological disorders in adults. Med Hypotheses. 1976;2:135-140.

14. Audebert M, Gendre JP, Le Quintrec Y. Folate and the nervous system (author’s transl). Sem Hop. 1979;55:1383-1387.

15. Young SN, Ghadirian AM. Folic acid and psychopathology. Prog Neuropsychopharmacol Biol Psychiatry. 1989;13:841-863.

16. Das UN. Folic acid says NO to vascular diseases. Nutrition. 2003;19:686-692.

17. Hyndman ME, Verma S, Rosenfeld RJ, et al. Interaction of 5-methyltetrahydrofolate and tetrahydrobiopterin on endothelial function. Am J Physiol Heart Circ Physiol. 2002;282:H2167-H2172.

18. Antoniades C, Shirodaria C, Warrick N, et al. 5-methyltetrahydrofolate rapidly improves endothelial function and decreases superoxide production in human vessels: effects on vascular tetrahydrobiopterin availability and endothelial nitric oxide synthase coupling. Circulation. 2006;114:1193-1201.

19. Stroes ES, van Faassen EE, Yo M, et al. Folic acid reverts dysfunction of endothelial nitric oxide synthase. Circ Res. 2000;86:1129-1134.

20. Doshi SN, McDowell IF, Moat SJ, et al. Folate improves endothelial function in coronary artery disease: an effect mediated by reduction of intracellular superoxide? Arterioscler Thromb Vasc Biol. 2001;21:1196-1202.

21. Verhaar MC, Wever RM, Kastelein JJ, et al. 5-methyltetrahydrofolate, the active form of folic acid, restores endothelial function in familial hypercholesterolemia. Circulation. 1998;97:237-241.

22. Lashner BA, Heidenreich PA, Su GL, et al. Effect of folate supplementation on the incidence of dysplasia and cancer in chronic ulcerative colitis. A case-control study. Gastroenterology. 1989;97:255- 259.

23. Lashner BA, Provencher KS, Seidner DL, et al. The effect of folic acid supplementation on the risk for cancer or dysplasia in ulcerative colitis. Gastroenterology. 1997;112:29-32.

24. Passeri M, Cucinotta D, Abate G, et al. Oral 5- methyltetrahydrofolic acid in senile organic mental disorders with depression: results of a double-blind multicenter study. Aging (Milano). 1993;5:63-71.

25. Godfrey PS, Toone BK, Carney MW, et al. Enhancement of recovery from psychiatric illness by methylfolate. Lancet. 1990;336:392-395.

26. Guaraldi GP, Fava M, Mazzi F, la Greca P. An open trial of methyltetrahydrofolate in elderly depressed patients. Ann Clin Psychiatry. 1993;5:101-105.

27. Coppen A, Bailey J. Enhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo controlled trial. J Affect Disord. 2000;60:121-130.

28. Coppen A, Chaudhry S, Swade C. Folic acid enhances lithium prophylaxis. J Affect Disord. 1986;10:9-13.

29. Botez MI, Peyronnard JM, Berube L, Labrecque R. Relapsing neuropathy, cerebral atrophy and folate deficiency. A close association. Appl Neurophysiol. 1979;42:171-183.

30. Liu T, Soong SJ, Wilson NP, et al. A case control study of nutritional factors and cervical dysplasia. Cancer Epidemiol Biomarkers Prev. 1993;2:525-530.

31. Grio R, Piacentino R, Marchino GL, Navone R. Antineoblastic activity of antioxidant vitamins:the role of folic acid in the prevention of cervical dysplasia. Panminerva Med. 1993;35:193-196.

32. Kwasniewska A, Tukendorf A, Semczuk M. Folate deficiency and cervical intraepithelial neoplasia. Eur J Gynaecol Oncol. 1997;18:526-530.

33. Butterworth CE Jr, Hatch KD, Gore H, et al. Improvement in cervical dysplasia associated with folic acid therapy in users of oral contraceptives. Am J Clin Nutr. 1982;35:73-82.

34. Vogel RI, Fink RA, Schneider LC, et al. The effectof folic acid on gingival health. J Periodontol. 1976;47:667-668.

35. Thomson ME, Pack AR. Effects of extended systemic and topical folate supplementation on gingivitis of pregnancy. J Clin Periodontol. 1982;9:275-280.

36. Pack AR. Folate mouthwash: effects on established gingivitis in periodontal patients. J Clin Periodontol. 1984;11:619-628.

37. Montes LF, Diaz ML, Lajous J, Garcia NJ. Folic acid and vitamin B12 in vitiligo: a nutritional approach. Cutis. 1992;50:39-42.

38. Juhlin L, Olsson MJ. Improvement of vitiligo after oral treatment with vitamin B12 and folic acid and the importance of sun exposure. Acta Derm Venereol. 1997;77:460-462.

39. Russell RM, Golner BB, Krasinski SD, et al. Effect of antacid and H2 receptor antagonists on the intestinal absorption of folic acid. J Lab Clin Med. 1988;112:458-463.

40. Lambie DG, Johnson RH. Drugs and folate metabolism. Drugs. 1985;30:145-155.

41. Pironi L, Cornia GL, Ursitti MA, et al. Evaluation of oral administration of folic and folinic acid to prevent folate deficiency in patients with inflammatory bowel disease treated with salicylazosulfapyridine. Int J Clin Pharmacol Res. 1988;8:143-148.

Optimal duration and quality of sleep is necessary for optimal health. Sleep disorders including insomnia, hypersomnia (excessive sleepiness), circadian rhythm disorders, restless leg syndrome, and sleep-disordered breathing are increasingly common. According to the National Institutes of Health, 50 to 70 million individuals in the United States are affected by chronic sleep disorders and intermittent sleep problems. In fact, nearly 7 out of 10 Americans state they experience frequent sleep problems, according to a recent poll.¹ In addition, the National Sleep Foundation’s 2009 poll stated that one-third of Americans report losing sleep over the state of the U.S. economy and other personal financial concerns.²

Inadequate sleep can significantly reduce quality of life, health, and safety. Sleep disorders have been associated with numerous diseases, as well as an increase in overall morbidity and mortality.³ This article will review the numerous diseases associated with lack of sleep and will describe natural ways individuals can obtain nourishing rest.

Cardiovascular Disease

Research indicates that sleep deprivation is associated with a significant increase in total cholesterol and low-density lipoprotein cholesterol (LDL) in women.⁴ A similar study found that in women, both short and long sleep durations are associated with elevated serum triglycerides and decreased levels of the beneficial high-density lipoprotein (HDL) cholesterol.⁵

Both short and long sleep durations are also associated with an increased prevalence of hypertension, with an even greater association with less than 6 hours of sleep per night.⁶ In a long-term study, researchers followed subjects without coronary heart disease for 10 years to evaluate sleep duration and the risk of coronary heart disease-related events. The researchers found that sleep duration less than 7 hours or greater than 9 hours of sleep per night is associated with a significant increase in the risk of coronary events.⁷ Evidence also indicates that the risk of metabolic syndrome increases by more than 45 percent in individuals reporting both short and long sleep duration, compared with those sleeping 7 to 8 hours per night.⁸

Mutagenic Concerns

Research suggests that disruption of circadian rhythms and sleep deprivation is associated with the development of certain cancers. Evidence indicates that women who work at night and who experience sleep deprivation, circadian disruption, and exposure to light-at-night are at an increased risk of breast cancer and possibly colorectal cancer.⁹ Additional data indicates that night work increases the risk of endometrial cancer in women,¹⁰ and the risk of non-Hodgkin lymphoma in men.¹¹ Other research indicates that disturbance of the circadian rhythms in flight personnel and shift workers also increase the risk of prostate cancer.¹²

Pain and Inflammation

Sleep disturbance is also associated with increased inflammation and related inflammatory diseases. Researchers have shown that sleep deprivation increased numerous pro-inflammatory mediators including C-reactive protein (CRP).¹³ Evidence indicates that more than 40 percent of individuals with insomnia symptoms report at least one chronic painful physical condition. Similarly, subjects with a chronic painful physical condition are more likely to have a shorter sleep duration and more frequent difficulty or inability to resume sleep once awake.¹⁴

In an interesting study, researchers evaluated the correlation of pain and sleep deprivation. The results showed that the number of reported sleep hours on the previous night was a highly significant predictor of the current day’s pain frequency. They found that either less than 6 or more than 9 hours of sleep correlated with greater next-day pain. Also, they showed that pain prospectively predicted sleep duration.¹⁵

Endocrine Disorders and Obesity

Currently, evidence suggests that sleep deprivation disturbs endocrine regulation of energy homeostasis, leading to weight gain and obesity. Research indicates that inadequate sleep adversely impacts numerous endocrine and metabolic functions, including decreased glucose tolerance and insulin sensitivity, increased levels of ghrelin and evening cortisol, decreased levels of leptin, and increased hunger and appetite. In addition, short sleep duration is associated with increased body mass index (BMI).¹⁶ This association is also evident in children. One study found that in young children who were persistently short-duration sleepers, less than 10 hours per night, the risk for overweight or obesity was almost 4.2 times higher compared to 11-hour persistent sleepers.¹⁷ Sleep deprivation is also associated with modulation in neuro-endocrine appetite control, showing a reduction in leptin, a hormone that promotes satiety, and increased levels of ghrelin, a hormone that increases hunger. These changes could lead to inaccurate signaling of caloric need in the nervous system.¹⁸ Sleep deprivation studies associate sleep restriction with decreased insulin sensitivity without compensation in pancreatic beta-cell function, resulting in an elevated risk of diabetes. In a 10-year follow-up study, researchers showed that subjects with sleep durations of 5 or fewer hours and of 9 or more hours were significantly more likely to develop diabetes.¹⁹

Neurological and Behavioral Disorders

Sleep deprivation causes a range of neurobehavioral changes such as slowed working memory, lapses of attention, reduced cognitive processing, and depressed mood. Neurobehavioral deficits accumulate with consecutive days of partial sleep loss, resulting in a level similar to total sleep deprivation. In fact, chronic sleep duration of less than 7 hours per night can result in cognitive dysfunction comparable to that seen after severe total sleep deprivation.²⁰ Functional imaging studies comparing sleep-deprived and well-rested brains provide substantial evidence that adequate sleep is important for optimal learning and cognitive function.²¹ Additionally, research indicates that even modest sleep deficits interfere with the enhancement of nerve cell production and growth associated with learning, and prolonged sleep deprivation may affect the overall rate of nerve cell proliferation.²² Also, adequate sleep is important for the maintenance and reorganization of neuronal circuits, including new synapse formation, allowing the brain to integrate learning and experiences.²³

Mood disorders are also strongly associated with insomnia. Research shows that approximately 28 percent of individuals with insomnia had a current diagnosis of mental disorders and over 25 percent had a psychiatric history. Additionally, this study showed that sleep disturbances appeared before or simultaneous with the development of the mood disorder.²⁴ Also, evidence indicates that there is a strong association between insomnia and depression, as depressed patients often show altered circadian rhythms and sleep disturbances.²⁵

Stress Response

Sleep deficits are also associated with an increased stress response. Both the sympathetic nervous system and the hypothalamus-pituitary-adrenal (HPA) axis increase in activity with sleep restriction. Researchers also propose that chronic sleep deprivation can lead to changes in the reactivity of the stress response to other stressors, which could sensitize individuals to stress-related disorders.²⁶ Research indicates that patients with insomnia have significantly increased evening and nocturnal levels of the stress hormone cortisol, and the levels of evening cortisol correlated with the number of nocturnal awakenings.²⁷

Natural Ways to Promote Healthy Sleep

A number of botanicals (each found in Herbal Sleep) have been used historically to promote healthy sleep. Both hops (Humulus lupulus)²⁸ and valerian (Valeriana officinalis) provide sedating properties. In one study, a combination of valerian and hops was supplemented in subjects with mild-moderate, non-organic insomnia for 2 weeks. The results showed that the herbal combination decreased sleep latency and wake time. Additionally, there was a decrease in stage 1 sleep with an increase in deeper, slow-wave sleep.²⁹ Research suggests that valerian supplementation is at least as effective as the pharmaceutical oxazepam in the treatment of non-organic insomnia. The study showed markedly increased sleep quality after 6 weeks compared to the beginning of the study. Also, 82.8 percent of subjects in the valerian group rated their treatment as very good.³⁰

Lemon balm (Melissa officinalis) is used by people with sleep disorders due to its calming effects and alertness reduction.³¹ In one study, both the amounts and quality of sleep in subjects improved with a combination of valerian and lemon balm.³² In a similar study using children with sleep disturbances, a valerian and lemon balm combination decreased sleep disturbance in 80.9 percent of the children, and decreased restlessness in 70.4 percent.³³

Magnolia bark extract is used in traditional Chinese and Japanese medicine. A derivative extracted from Magnolia bark has shown anxiety-reducing activity in animal models similar to that of the pharmaceutical diazepam, used for treating anxiety disorders. Also, unlike diazepam, the Magnolia constituent did not cause dependency and withdrawal symptoms, central nervous system depression, or learning and memory disturbances.³⁴ In a human study, a combination product including Magnolia bark extract was used to treat symptomatic menopausal women for 24 weeks. The results of the study showed a decrease in numerous menopausal complaints including insomnia, anxiety, depression, and irritability.³⁵ Similarly, passionflower (Passiflora incarnate) has been used medicinally to treat anxiety disorders and insomnia. In one study, passionflower was shown to be equally as effective as the pharmaceutical benzodiazepine oxazepam in the treatment of generalized anxiety disorder, and with less impairment in job performance.³⁶ Ziziphus spinosa is also used in traditional Chinese medicine for sedation in the treatment of insomnia. Using animal models, constituents of this herb have shown to prolong sleeping time.³⁷

Conclusion

Insufficient sleep is becoming increasingly common. There is an immense amount of research that indicates deficient sleep is a risk factor for a number of diseases and physiological dysfunctions. Thus, it is imperative to optimize sleep to decrease the risk of developing these disorders and improving overall health. The botanicals hops, valerian, lemon balm, magnolia bark, passionflower, and Ziziphus spinosa (all found in Herbal Sleep) can encourage a restful night’s slumber, helping one feel relaxed and refreshed.

References

1. National Sleep Foundation. Sleep Studies. Available at: http://www.sleepfoundation.org/site/c.huIXKjM0IxF/b.4813333/k.93F2/Sleep_Studies.htm. Accessed On: 04-06-09.

2. National Sleep Foundation. 2009 Sleep in America^™ Poll Results. Available at: www.sleepfoundation.org. Accessed on: 04-06-09.

3. Mullington JM, Haack M, Toth M, et al. Cardiovascular, inflammatory, and metabolic consequences of sleep deprivation. Prog Cardiovasc Dis. 2009 Jan-Feb;51(4):294-302.

4. Kerkhofs M, Boudjeltia KZ, Stenuit P, et al. Sleep restriction increases blood neutrophils, total cholesterol and low density lipoprotein cholesterol in postmenopausal women: A preliminary study. Maturitas. 2007 Feb 20;56(2):212-5.

5. Kaneita Y, Uchiyama M, Yoshiike N, et al. Associations of usual sleep duration with serum lipid and lipoprotein levels. Sleep. 2008 May 1;31(5):645-52.

6. Gottlieb DJ, Redline S, Nieto FJ, et al. Association of usual sleep duration with hypertension: the Sleep Heart Health Study. Sleep. 2006 Aug 1;29(8):1009-14.

7. Ayas NT, White DP, Manson JE, et al. A prospective study of sleep duration and coronary heart disease in women. Arch Intern Med. 2003 Jan 27;163(2):205-9.

8. Hall MH, Muldoon MF, Jennings JR, et al. Self-reported sleep duration is associated with the metabolic syndrome in midlife adults. Sleep. 2008 May 1;31(5):635-43.

9. Davis S, Mirick DK. Circadian disruption, shift work and the risk of cancer: a summary of the evidence and studies in Seattle. Cancer Causes Control. 2006 May;17(4):539-45.

10. Viswanathan AN, Schernhammer ES. Circulating melatonin and the risk of breast and endometrial cancer in women. Cancer Lett. 2008 Dec 11. Published Online Ahead of Print.

11. Lahti TA, Partonen T, Kyyrönen P, et al. Night-time work predisposes to non-Hodgkin lymphoma. Int J Cancer. 2008 Nov 1;123(9):2148-51.

12. Erren TC, Pape HG, Reiter RJ, et al. Chronodisruption and cancer. Naturwissenschaften. 2008 May;95(5):367-82.

13. van Leeuwen WM, Lehto M, Karisola P, et al. Sleep restriction increases the risk of developing cardiovascular diseases by augmenting proinflammatory responses through IL-17 and CRP. PLoS ONE. 2009;4(2):e4589.

14. Ohayon MM. Relationship between chronic painful physical condition and insomnia. J Psychiatr Res. 2005 Mar;39:151-159.

15. Edwards RR, Almeida DM, Klick B, et al. Duration of sleep contributes to next-day pain report in the general population. Pain. 2008 Jul;137(1):202-7.

16. Van Cauter E, Knutson KL. Sleep and the epidemic of obesity in children and adults. Eur J Endocrinol. 2008 Dec;159 Suppl 1:S59-66.

17. Touchette E, Petit D, Tremblay RE, et al. Associations between sleep duration patterns and overweight/obesity at age 6. Sleep. 2008 Nov 1;31(11):1507-14.

18. Knutson KL, Van Cauter E. Associations between sleep loss and increased risk of obesity and diabetes. Ann N Y Acad Sci. 2008;1129:287-304.

19. Gangwisch JE, Heymsfield SB, Boden-Albala B, et al. Sleep duration as a risk factor for diabetes incidence in a large U.S. sample. Sleep. 2007 Dec 1;30(12):1667-73.

20. Banks S, Dinges DF. Behavioral and physiological consequences of sleep restriction. J Clin Sleep Med. 2007 Aug 15;3(5):519-28.

21. Chee MW, Chuah LY. Functional neuroimaging insights into how sleep and sleep deprivation affect memory and cognition. Curr Opin Neurol. 2008 Aug;21(4):417-23.

22. Meerlo P, Mistlberger RE, Jacobs BL, et al. New neurons in the adult brain: The role of sleep and consequences of sleep loss. Sleep Med Rev. 2008 Oct 9. Published Online Ahead of Print.

23. Montes-Rodríguez CJ, Rueda-Orozco PE, Urteaga-Urías E, et al. From neuronal recovery to the reorganisation of neuronal circuits: a review of the functions of sleep. Rev Neurol. 2006 Oct 1-15;43(7):409-15.

24. Ohayon MM, Roth T. Place of chronic insomnia in the course of depressive and anxiety disorders. J Psychiatr Res. 2003 Jan-Feb;37:9-15.

25. Germain A, Kupfer DJ. Circadian rhythm disturbances in depression. Hum Psychopharmacol. 2008 Oct;23(7):571-85.

26. Meerlo P, Sgoifo A, Suchecki D. Restricted and disrupted sleep: effects on autonomic function, neuroendocrine stress systems and stress responsivity. Sleep Med Rev. 2008 Jun;12(3):197-210.

27. Rodenbeck A, Huether G, Rüther E, et al. Interactions between evening and nocturnal cortisol secretion and sleep parameters in patients with severe chronic primary insomnia. Neurosci Lett. 2002 May 17;324:159-163.

28. Schiller H, Forster A, Vonhoff C, et al. Sedating effects of Humulus lupulus L. extracts. Phytomedicine. 2006 Sep;13(8):535-41.

29. Fussel A, Wolf A, Brattstrom A. Effect of a fixed valerian-Hop extract combination (Ze 91019) on sleep polygraphy in patients with non-organic insomnia: a pilot study. Eur J Med Res. 2000 Sep 18;5:385-390.

30. Ziegler G, Ploch M, Miettinen-Baumann A, et al. Efficacy and tolerability of valerian extract LI 156 compared with oxazepam in the treatment of non-organic insomnia—a randomized, double-blind, comparative clinical study. Eur J Med Res. 2002 Nov 25;7:480-486.

31. Kennedy DO, Scholey AB, Tildesley NT, et al. Modulation of mood and cognitive performance following acute administration of Melissa officinalis (lemon balm). Pharmacol Biochem Behav. 2002;72:953-964.

32. Cerny A, Shmid K. Tolerability and efficacy of valerian/lemon balm in healthy volunteers (a double blind, placebo-controlled, multicentre study). Fitoterapia. 1999;70:221-228.

33. Müller SF, Klement S. A combination of valerian and lemon balm is effective in the treatment of restlessness and dyssomnia in children. Phytomedicine. 2006 Jun;13:383-387.

34. Kuribara H, Stavinoha WB, Maruyama Y. Honokiol, a putative anxiolytic agent extracted from magnolia bark, has no diazepam-like side-effects in mice. J Pharm Pharmacol. 1999 Jan;51(1):97-103.

35. Mucci M, Carraro C, Mancino P, et al. Soy isoflavones, lactobacilli, Magnolia bark extract, vitamin D3 and calcium. Controlled clinical study in menopause. Minerva Ginecol. 2006 Aug;58(4):323-34.

36. Akhondzadeh S, Naghavi HR, Vazirian M, et al. Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam. J Clin Pharm Ther. 2001 Oct;26:363-367.

37. Jiang JG, Huang XJ, Chen J, et al. Comparison of the sedative and hypnotic effects of flavonoids, saponins, and polysaccharides extracted from Semen Ziziphus jujube. Nat Prod Res. 2007 Apr;21(4):310-20.

Seasonal allergies (allergic rhinitis) have become an all-too-common problem among the population. According to a recent study, 65 million people in the United States suffer from self-reported, physician-diagnosed seasonal or perennial allergic rhinitis.¹ The same study concluded that almost one-half of Americans experience troublesome nasal symptoms on at least 7 days throughout the year, with most attributing their symptoms to allergies.¹

A process that is so essential for the reproduction of plants—the release of pollen into the air—can be detrimental to human airways, causing symptoms of allergies and asthma. Allergic rhinitis falls into two categories: Seasonal and perennial. Seasonal allergic rhinitis occurs particularly during pollen season and does not usually develop until after 6 years of age. Perennial allergies occur throughout the year and can be seen in younger children as well as adults.

In individuals whose immune systems have become sensitized, inhaling allergens such as pollen or dust results in antibody production. These antibodies mostly bind to mast cells. When allergens come in contact with the antibodies, it triggers the release of histamine and other chemicals from the mast cells. This results in the itching, swelling, and mucus production experienced by allergy sufferers. The symptomatic response to pollen can also be caused by white blood cells known as granulocytes, which are similar to mast cells and produce inflammation, due in part to oxidative stress.²

Another key factor involved in allergic rhinitis is secretory immunoglobulin A (sIgA). Secretory IgA is the principal protective antibody in exocrine secretions such as from the salivary glands, and mucous membranes such as the respiratory and gastrointestinal tract. The maintenance of sufficient sIgA is critical in protecting mucosal surfaces from invasion by pathogenic bacteria, viruses and inert foreign macromolecules, such as pollen, that are involved in seasonal allergies. Individuals who are prone to allergic rhinitis have been shown to have lower levels of secretory IgA.³

Natural killer cells also play a role in immune system support in allergy patients. Researchers have found that allergic diseases are accompanied by a partial impairment of the natural killer cell capability of promoting and maintaining appropriate T helper cell immune responses.⁴

The sneezing, coughing, excess mucous production and watery eyes that occur during an allergy episode can severely impact quality of life, draining energy and preventing allergy sufferers from fully enjoying what would normally be pleasant time spent outdoors.

A proactive stance is essential to deflecting the frustrating symptoms associated with this condition. Key to this approach is strengthening immunity. This article will review one of the most effective substances shown to support the health of individuals with seasonal allergies and will address lifestyle modifications that can help ease the burden.

EpiCor^® and Allergies

One of the key ways that EpiCor, an end product of fermentation of baker’s yeast (Saccharomyces cerevisiae), enhances immunity is through its ability to increase levels of sIgA. Researchers have demonstrated that subjects given EpiCor have significantly higher levels of total salivary secretory IgA.⁵ This indicates that subjects taking EpiCor had the equivalent of an immunological envelope protecting all the membranes in the eyes, nasal passages, and all the places where pathogenic organisms enter into the system.

Studies also have shown that natural killer cells in EpiCor-exposed subjects had a much higher killing efficiency of pathogen-infected and abnormal cells despite a significant decrease in the natural killer cells’ number, indicating the EpiCor increased the efficiency of the natural killer cells. At the same time, subjects exposed to EpiCor experienced a significant inhibition of interferon gamma production, significantly lower levels of immune complexes and higher levels of glutathione in erythrocytes (red blood cells), which indicates that EpiCor has anti-inflammatory abilities.⁶

EpiCor’s ability to inhibit interferon gamma production is especially interesting. Even though NK cells produce interferon gamma as part of the defense mechanism against invading pathogens and tumor cells, when interferon gamma is produced in too large quantities, it can actually impair immunity. A healthy immune system remains in a state of balance, carefully regulating interferon gamma levels to ensure there is not an oversupply (which would cause a greater risk of infection and cancer). An excessive amount of interferon gamma results in an overabundance of NK cells, which can cause autoimmune diseases and increase susceptibility to allergies.⁷

In fact, antihistamines used for seasonal allergies are known to inhibit interferon gamma as part of their mechanism of action.⁸

EpiCor’s ability to strengthen the immune system recently led researchers to test its effects in allergy sufferers.⁹ In the randomized, double-blind, placebo-controlled clinical trial, 84 healthy subjects who tested positive for seasonal allergies were randomized to take EpiCor 500 mg once per day or a placebo. The trial was conducted during the 12 weeks of spring and summer when total pollen counts are high. The highest total pollen counts occurred during the first 6 weeks of the clinical trial. Because of this, the researchers looked at the first 6 weeks of results since most allergy-related symptoms would occur during high pollen counts.

EpiCor significantly reduced the mean severity of nasal symptoms, including a significant reduction in runny nose, and a significant reduction in nasal congestion. EpiCor reduced both eye discharge severity and the number of days with eye discharge compared to placebo. EpiCor also demonstrated the greatest reductions in symptom severity when total pollen counts were highest. The severity of runny nose, congestion, and total nasal symptoms were significantly reduced. The largest symptomatic impact occurred with nasal congestion where the EpiCor group experienced approximately a total of 6 fewer congestive days compared to placebo (17 days vs. 23).

Subjects were also asked to record when they used over-the-counter allergy medication for severe allergies. Subjects taking EpiCor used significantly less rescue medication for allergies compared to placebo during the highest pollen count period. Serum and especially nasal smear data mirrored the effectiveness observed in the allergy diary and questionnaire.⁹

Lifestyle Measures

In addition to using EpiCor, individuals with allergic rhinitis can implement certain lifestyle changes. First, it’s important to be aware of any cross-reactivity that is occurring due to similarities in the proteins of pollen and food.^10-11 One example is a person who is allergic to birch pollen may also react to the skin of apples or potatoes.¹² An itchy throat after eating an apple or sneezing when peeling potatoes or apples is an indication that this cross reactivity may be occurring. A Food Allergy Test, which tests for sensitivities to 96 different foods, is available here and is the best way to determine which food sensitivities may be compounding an individual’s seasonal allergy problem.

Other lifestyle modifications include:

• Use the air conditioner rather than opening a window.
• Keep track of pollen counts in your area and don’t exercise outside during your allergen peak.
• Keep car windows up and sunroof closed and keep air on re-circulate while driving.
• Shower prior to going to bed including your hair, because pollen will collect on you throughout the day.

Conclusion

Spring and early summer can be a particularly challenging time of year for individuals who suffer from allergic rhinitis. Supplementing with EpiCor and taking a food allergy test to determine which food sensitivities may be increasing ones susceptibility to seasonal allergies can serve as a two-part approach to help allergy sufferers strengthen their immune systems.

References

1. Nathan RA, Meltzer EO, Derebery J, Campbell UB, Stang PE, Corrao MA, Allen G, Stanford R. The prevalence of nasal symptoms attributed to allergies in the United States: findings from the burden of rhinitis in an America survey. Allergy Asthma Proc. 2008 Nov-Dec;29(6):600-8.

2. Ritsick DR, Lambeth JD. Spring brings breezes, wheezes, and pollen oxidases. J Clin Invest. 2005 Aug;115(8):2067-9.

3. Cortesina G, Carlevato MT, Bussi M, Baldi C, Majore L, Ruffino C. Mucosal immunity in allergic rhinitis. Acta Otolaryngol. 1993 May;113(3):397-9.

4. Scordamaglia F, Balsamo M, Scordamaglia A, Moretta A, Mingari MC, Canonica GW, Moretta L, Vitale M. Perturbations of natural killer cell regulatory functions in respiratory allergic diseases. J Allergy Clin Immunol. 2008 Feb;121(2):479-85.

5. Jensen GS, Patterson KM, Barnes J, et al. 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.

6. 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.

7. Yu J, Wei M, Becknell B, Trotta R, Liu S, Boyd Z, Jaung MS, Blaser BW, Sun J, Benson DM Jr, Mao H, Yokohama A, Bhatt D, Shen L, Davuluri R, Weinstein M, Marcucci G, Caligiuri MA. Pro- and Antiinflammatory Cytokine Signaling: Reciprocal Antagonism Regulates Interferon-gamma Production by Human Natural Killer Cells. Immunity. 2006 May;24(5):575-90.

8. Iida H, Asada H, Yokoi S, Niizeki H, Yasuda Y, Miyagawa S, Kita E. Regulatory effects of antihistamines on the responses to staphylococcal enterotoxin B of human monocyte-derived dendritic cells and CD4+ T cells. J Dermatol Sci. 2008 Oct;52(1):31-8.

9. Moyad MA, Robinson LE. Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Effect of 500 mg Once a Day EpiCor on Allergy Symptoms. Unpublished study.

10. Czaja-Bulsa G, Bachórska J. Food allergy in children with pollinosis in the Western sea coast region. Pol Merkur Lekarski. 1998;5(30): 338–40.

11. Malandain H. Allergies associated with both food and pollen. Allerg Immunol (Paris). 2003; 35 (7):253–6.

12. Yamamoto T, Asakura K, Shirasaki H, Himi T, Ogasawara H, Narita S, Kataura A (2005). Relationship between pollen allergy and oral allergy syndrome. Nippon Jibiinkoka Gakkai Kaiho. 108 (10): 971–9.

Stress is an all-too-real aspect of everyone’s life, but never more so than now, with the added tensions of job losses, home foreclosures, and other factors related to the poor economy. Some stress is normal and is an inescapable aspect of life. Certainly, a life free of stress and devoid of challenges would be filled with boredom and hardly worth living. The most memorable events in life tend to be those that are the most stressful—situations that require us to rise to a challenge and push past our normal limits. It is, therefore, how we adapt to stress that will make the difference between maintaining optimal health or weakening the body to the extent that it is susceptible to illness.

The adrenal glands and the hormones they produce are the body’s primary coping mechanism in regards to stress. During chronic stress, proper functioning of these glands is essential. However, the irony is that chronic stress can actually impair the function of the adrenal glands.

Overt adrenal diseases such as Addison’s or Cushing’s disease are quite rare. However, sub-clinical adrenal dysfunction caused by chronic stress is increasingly common. Chronic stress accompanied by adrenal dysfunction is usually characterized by fatigue and can predispose an individual to a number of conditions including heart disease¹ and depression.² Stress also reactivates chronic inflammation and may trigger the relapse of inflammatory bowel disease such as colitis.³

Therefore, reducing the effect of stress on the body is beneficial not only to peace of mind but also to overall health. This article will explain how adaptogens, respected throughout time for their ability to nourish the adrenal glands, can help reduce the effects of stress. However, prior to presenting the research on these adaptogens, it’s important to review how stress affects the body.

Adapting to Stress

A key factor in the maintenance of resistance to stress is the hypothalamo-pituitary-adrenal axis. Stressors excite the hypothalamus to produce adrenocorticotropic hormone (ACTH), which induces the adrenal cortex to secrete glucocorticoids (principally cortisone) and DHEA, and the adrenal medulla to secrete epinephrine and norepinephrine. When cortisone levels rise, they inhibit the hypothalamus and pituitary, which in turn decrease corticotropin releasing hormone (CRH) and ACTH production, respectively. When blood cortisone levels decrease, hypothalamic activity increases, releasing CRH. This increases pituitary ACTH output, which stimulates the adrenal cortex to increase blood cortisone levels. In this cyclic manner, equilibrium is maintained in the system.

Cortisone concentrations in the blood undergo cyclic, diurnal (circadian) changes. These changes are due to variations in CRH and ACTH output, as well as to changes in hypothalamic and central nervous system sensitivity to cortisol. With normal diurnal rhythm, blood ACTH levels rise between 3 and 6 AM, causing increases in blood cortisol. Thus, blood cortisol concentrations are at their highest in the morning. These peak levels gradually decrease, dropping to minimal levels by night. Under normal conditions, basal morning cortisol concentrations are twice those at night.

Cortisone is “the hormone of life” and without it we would be unable to adapt to various stressors. However, when produced in excess over a prolonged period, it has a number of adverse, damaging effects. These include elevations of blood sugar, sodium retention (resulting in hypertension), suppression of immunity, gastric ulcers, headaches, loss of bone density, and even heart attacks. Excess cortisol can also accelerate aging.

Natural Support for Adrenal Dysfunction

Adaptogens are botanicals that augment resistance to stress, and increase concentration, performance and endurance during fatigue. Adaptogens are known for their ability to nourish the adrenal glands and therefore strengthen the body’s ability to cope with stress. In order to be classified as an adaptogen, a plant must have four general properties: (1) It is harmless to the host; (2) It has a general, rather nonspecific, effect; (3) It increases the resistance of the recipient to a variety of physical, chemical, or biological stressors; and (4) It acts as a general stabilizer/normalizer.⁴

Some of the most powerful adaptogens include Eleutherococcus senticosus root, Manchurian Thorn Tree (Aralia manchurica) root, and Schisandra (Schisandra chinensis) fruit. These botanicals are known for their ability to reduce the effects of stress, improve stamina, and reduce fatigue.

Eleutherococcus senticosus

Eleutherococcus senticosus has been found to decrease adrenal hypertrophy and the subsequent depletion of adrenal vitamin C levels in stressed rodents.⁵ Animals given this adaptogen also have increased the amount of time they could swim to exhaustion, indicating it has a stamina-enhancing effect.^5-6

The botanical has exerted an equally promising effect in humans. In a double-blind study, researchers randomized 45 healthy volunteers (20 men, 25 women; ages 18-30) to receive Eleutherococcus senticosus or a placebo for 30 days. Patients’ response to stressors were measured, along with heart rate, and systolic and diastolic blood pressure, before and after using Eleutherococcus. Compared to the placebo group, those subjects using the adaptogen experienced a 40-percent reduction in heart rate response to stress. Additionally, in females but not males, the use of Eleutherococcus resulted in a 60-percent reduction in systolic blood pressure response to a cognitive challenge test.⁷ The study suggests Eleutherococcus may help the body adapt to stress.⁴

Manchurian Thorn Tree

Manchurian Thorn Tree (Aralia manchurica) is another adaptogen known for its ability to stabilize blood sugar levels. In any condition characterized by adrenal dysfunction, it is extremely important to stabilize blood sugar—whether it is too high or too low—alleviating a major metabolic stress on the body. Studies have shown that adaptogens like Aralia help achieve extra stamina and energy by enhancing utilization of glucose. In animal studies, Aralia extracts have acted as hypoglycemic agents.^8-9

Schisandra chinensis

As a result of the large number of pharmacological and clinical studies carried out by Russian scientists on Schisandra chinensis, this botanical first gained recognition as an adaptogen and an official medicine of the USSR in the early 1960s. Studies on animals have shown that Schizandra increases physical working capacity and affords a stress-protective effect against a broad spectrum of harmful factors including heat shock, skin burn, frostbite, swimming under load in an atmosphere with decreased air pressure, irradiation, and heavy metal intoxication. Schizandra exerts a beneficial effect on the central nervous, sympathetic, endocrine, immune, respiratory, cardiovascular, and gastrointestinal systems.

In healthy subjects, Schizandra increases endurance and accuracy of movement, mental performance and working capacity, and generates alterations in the basal levels of nitric oxide and cortisol in blood and saliva with subsequent effects on the blood cells, vessels and the central nervous system. Numerous clinical trials have demonstrated the efficiency of Schizandra in psychiatric disorders such as neurosis, depression, schizophrenia and alcoholism, cardiotonic disorders, epidemic waves of influenza,  chronic sinusitis, otitis, neuritis, pneumonia, allergic dermatitis, acute gastrointestinal diseases, stomach, duodenal and trophic ulcers, and wound healing.¹⁰ Schisandra also has been found to reduce the levels of corticosterone and glucose and protect the structure of the adrenal cortex in animals exposed to stress.¹¹

Conclusion

Chronic Stress and the adrenal gland’s inability to cope with it may be responsible for a host of common diseases. A number of powerful adaptogens (all found in AdaptaPhase^® 1) can help strengthen the adrenal glands including Eleutherococcus senticosus root, Manchurian Thorn Tree (Aralia manchurica) root, and Schisandra (Schisandra chinensis) fruit. This combination is designed to help strengthen the body’s defenses against stress, ensuring optimal health and enhanced energy levels.

References

1. Ziegelstein RC. Acute emotional stress and cardiac arrhythmias. JAMA. 2007 Jul 18;298(3):324-9.

2. Mizoguchi K, Shoji H, Ikeda R, Tanaka Y, Tabira T. Persistent depressive state after chronic stress in rats is accompanied by HPA axis dysregulation and reduced prefrontal dopaminergic neurotransmission. Pharmacol Biochem Behav. 2008 Nov;91(1):170-5.

3. Melgar S, Engström K, Jägervall A, Martinez V. Psychological stress reactivates dextran sulfate sodium-induced chronic colitis in mice. Stress. 2008;11(5):348-62.

4. Authors unlisted. Eleutherococcus senticosus. Monograph. Alternative Medicine Review. 2006; 11(2): 151-155.

5. Mills S, Bone K. Principles and Practice of Phytotherapy. New York, NY: Churchill Livingston; 2000:536.

6. Nishibe S, Kinoshita H, Takeda H, Okano G. Phenolic compounds from stem bark of Acanthopanax senticosus and their pharmacological effect in chronic swimming stressed rats. Chem Pharm Bull (Tokyo). 1990;38:1763-1765.

7. Facchinetti F, Neri I, Tarabusi M. Eleutherococcus senticosus reduces cardiovascular response in healthy subjects: a randomized, placebo-controlled trial. Stress Health. 2002;18:11-17.

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

9. Yoshikawa M, Murakami T, Harada E, Murakami N, Yamahara J, Matsuda H. Bioactive saponins and glycosides. VII. On the hypoglycemic principles from the root cortex of Aralia elata Seem.: structure related hypoglycemic activity of oleanolic acid oligoglycoside. Chem Pharm Bull (Tokyo). 1996;44(10):1923-7.

10. Panossian A, Wikman G. Pharmacology of Schisandra chinensis Bail.: an overview of Russian research and uses in medicine. J Ethnopharmacol. 2008 Jul 23;118(2):183-212.

11. Sun LJ, Wang GH, Wu B, Wang J, Wang Q, Hu LP, Shao JQ, Wang YT, Li J, Gu P, Lu B. [Effects of schisandra on the function of the pituitary-adrenal cortex, gonadal axies and carbohydrate metabolism in rats undergoing experimental chronic psychological stress, navigation and strenuous exercise]. Zhonghua Nan Ke Xue. 2009 Feb;15(2):126-9.

Inflammatory Bowel Disease (IBD) is a real problem primarily seen in cats and less frequently dogs. This is not the same problem that the human animal has. Their IBD is irregular and often prolonged contractions of the bowel wall.

IBD in animals is a disease that decreases the body’s ability to digest and absorb nutrients. The small bowel becomes thickened and inflamed, which can cause underlying discomfort with the inability to thrive. Ultimately, this becomes an issue of intestinal motility.

Signs that your cat may have IBD may be vomiting, which is usually chronic and intermittent, diarrhea or constipation. Chronic vomiting can be as often as once per month or more. Anything more than one or two hairballs vomited up in a year is a clue. The diarrhea or constipation can alternate or can stay consistent as one or the other. The most common clinical sign seen is weight loss.

While there seems to be a genetic predisposition, dietary allergens play a huge role along with changes in the intestinal bacterial population. Genetics aside, dietary allergies are seen in both cats and dogs. The biggest problem is diagnosis.

Normally, to make a diagnosis, your veterinarian will want a minimum database that would include a CBC/chemistry and urinalysis. Sadly, the results are typically normal or may show mild increases in some of the tests. X-rays are taken to rule out things like foreign bodies or masses in the abdomen.

To make the actual diagnosis of IBD, an endoscopy (examining the intestinal tract using a fiberscope placed through the mouth and stomach under anesthesia) or exploratory surgery is necessary. The diagnosis is made by microscopic examination of the tissue of the small bowel. Therefore, tissue biopsy is a must to make an absolute diagnosis and the above procedures allow us to harvest the necessary tissue.

Once the diagnosis is made, your veterinarian will likely set up a treatment plan which may include such drugs as prednisone, (a glucocorticoid), Leukeran® (a chemotherapy agent) and/or metronidazole (an antibiotic). Dietary change may be done through the use of prescription diets or home cooked meals that are very low in carbohydrates.

I started using N-acetyl-glucosamine in cats a number of years ago and found it to be quite worthwhile. NAG is a building block of the intestinal mucosa and it seemed to make some sense. This all started when we had a couple of cats that did not respond to conventional therapy. When they were given 200 mg of NAG twice daily, the results were quite dramatic and the conventional therapy dose was reduced to very minimal levels. Both cats lived long and healthy lives. I’ve been very pleased with the results since then and used the product by itself many times.

Interestingly, the product Lectin Lock™, has NAG along with other ingredients that tie up lectins, the little remnants of sacchride (sugar) breakdown that are resistant to digestion and can end up in the cells causing irritation/inflammation. This may be a component of IBD although I am unable to find a direct reference to it in the animal literature. Regardless, Lectin Lock has several different ingredients that help capture these lectins and transport them out of the alimentary canal. I would use ½ to one capsule twice daily on the average cat and one to two capsules twice per day on a dog. After three to six weeks, if there is good response, I would decrease the dose to once per day.

I haven’t seen a case of IBD in the last couple of years and if I did today, I would use the Lectin Lock along with the probiotic formula BioPRO™ to stabilize the correct kind of bacteria in the bowel tract.

Melatonin May Improve Mood Disorder and Stress Response

According to the data from the National Health and Nutrition Examination Survey (NHANES) 2005-2006,  more than 1 in 20 Americans 12 years of age and older currently experience depression. Depression is characterized by a depressed, sad or irritable mood; loss of interest in usual activities; inability to experience pleasure; feelings of guilt or worthlessness; and thoughts of death or suicide that cause impairment in daily functioning. Individuals suffering from depression may also report inability to concentrate, difficulty making decisions, fatigue, feeling either restless or slowed down, changes in sleep, and changes in appetite. Interestingly, depressed patients may present with changes in circadian and seasonal rhythms as well.

In a new study, melatonin was evaluated for effects on depression and the stress response, as stress plays a major role in the development of depression. Melatonin is a hormone secreted primarily from the pineal gland in the brain, and is important for numerous physiological functions including regulating circadian rhythms, and supporting immune function. It is a potent antioxidant and plays a role in the stress response.

In this study, melatonin was compared to the tricyclic antidepressant imipramine in an experimental mouse model of depression. The mice were evaluated for changes in the sheen of their fur, grooming behavior and corticosterone levels induced by unpredictable chronic mild stress. Corticosterone is one of the steroid hormones secreted from the adrenal gland, which is important in the stress response. The adrenal glands play a significant role in the hypothalamus-pituitary-adrenal (HPA) axis, which is often up-regulated during acute and chronic stress.

After 5 weeks of exposing the mice to unpredictable chronic mild stress, the mice exhibited significant loss of luster of their fur, decreased grooming, and an increase in serum corticosterone levels. Supplementation with melatonin or imipramine reversed these findings.

The researchers concluded that “especially in view of the relevance of stress as a major contributing factor in depression, as well as the alleged importance of normalizing a hyperfunctioning HPA axis and resynchronizing circadian rhythms for a successful treatment of depression, this study reassesses the potential of melatonin as an antidepressant.”

Reference:

Detanico BC, Piato AL, Freitas JJ, Lhullier FL, Hidalgo MP, Caumo W, Elisabetsky E. Antidepressant-like effects of melatonin in the mouse chronic mild stress model. Eur J Pharmacol. 2009 Apr 1;607(1-3):121-5.

Omega-3 Fatty Acids Important for Prostate Health

In a recent study, scientists evaluated omega-3 fatty acid intake and genetic variations in regards to prostate cancer. This study looked at 9 genetic variants in the cyclooxygenase-2 (COX-2) gene, which encodes for the COX-2 enzyme. This enzyme is important in inflammation and fatty acid metabolism.

In this study, 466 men with aggressive prostate cancer and 478 age and ethnicity matched healthy men were evaluated.  Dietary intake of omega-3 fatty acids was assessed by a food frequency questionnaire. Genetic variations, known as single nucleotide polymorphisms (SNP), for the COX-2 gene were also evaluated.

The results showed that increased intake of long chain omega-3 fatty acids is strongly associated with a decreased risk of aggressive prostate cancer. The study showed a 63 percent reduced risk of aggressive prostate cancer in the men who consumed the highest amount of long-chain omega-3 fatty acids compared to men with the lowest intake of long chain omega-3 fatty acids.

Additionally, the researchers found that a particular SNP, rs4648310, modulated these findings. What they found was that men with low long chain omega-3 fatty acid intake and this genetic variant had an increased risk of disease. In fact, this group had greater than a five-fold increased risk of advanced prostate cancer. However, the researchers also found that increased omega-3 intake in the men with this genetic variant reversed this increase in disease risk.

Thus, the study authors concluded that “dietary long chain omega-3 polyunsaturated fatty acids appear protective for aggressive prostate cancer, and this effect is modified by the COX-2 SNP rs4648310. Our findings support the hypothesis that long chain omega-3 may impact prostate inflammation and carcinogenesis through the COX-2 enzymatic pathway.”

Reference:

Fradet V, Cheng I, Casey G, Witte JS. Dietary Omega-3 Fatty Acids, Cyclooxygenase-2 Genetic Variation, and Aggressive Prostate Cancer Risk. Clin Cancer Res. 2009 Mar 24. Published Online Ahead of Print.

Multivitamins Decrease Age-Related Change

A new study found that multivitamin intake influences a key factor involved in aging.

Chromosomes are comprised of strands of DNA, which carry the genetic material in cells. At the end of the chromosome, there is an area of repeat sequences called the telomere, which provides protection and stabilization for the chromosome. In general, telomeres shorten with each replication of the DNA when a cell divides. Thus telomere length is used as a marker of cellular and biological aging, as shorter telomeres are associated with increased age-related changes.

In a new study, 586 women between the ages of 35 and 74 years old were given a questionnaire to assess multivitamin use and dietary nutrient intake. Also, the relative telomere length of leukocyte (white blood cell) DNA was measured using a procedure known as quantitative polymerase chain reaction. The results showed that multivitamin use was associated with longer telomeres. In fact, the relative telomere length was an average of 5.1 percent longer in subjects that take multivitamins daily compared to subjects who did not take multivitamins. In addition, higher dietary intake of vitamin C and vitamin E were also associated with longer telomere length.

The researchers suggest that this may be due to the micronutrients modulating oxidative stress and chronic inflammation.

According to the researchers, “This study provides the first epidemiologic evidence that multivitamin use is associated with longer telomere length among women.”

Reference:

Xu Q, Parks CG, DeRoo LA, Cawthon RM, Sandler DP, Chen H. Multivitamin use and telomere length in women. Am J Clin Nutr. 2009 Mar 11. Published Online Ahead of Print.

CoQ10 Improves Blood Flow in Subjects on Statins

A new study found that CoQ10 supplementation may benefit vascular health in type 2 diabetic patients taking statin drugs.

In the United States, there are an estimated 23.6 million people with diabetes and another 57 million individuals with pre-diabetes. Patients with diabetes are at increased risk of cardiovascular disease and cardiovascular-related mortality. In fact, adults with diabetes have heart-disease-related death rates approximately 2-4 times higher than adults without diabetes.

Often, statin drugs, also know as HMG-CoA reductase inhibitors, are prescribed for diabetic patients to treat their elevated cholesterol levels. This class of drugs works by inhibiting the enzyme HMG-CoA reductase, which is involved in cholesterol synthesis. By inhibiting this enzyme, these drugs also inhibit the synthesis of the potent antioxidant Coenzyme Q10 (CoQ10).

In a new randomized, double-blind study, researchers selected subjects with type 2 diabetes, low density lipoprotein (LDL) cholesterol less than 2.5 mmol/L and brachial artery flow-mediated dilatation less than 5.5 percent. Reduced flow-mediated dilatation is a sign of endothelial dysfunction, an abnormal functioning of the inner lining of blood vessels, resulting in the inability to dilate fully upon stimulation. Endothelial dysfunction is a key factor in the development of atherosclerosis. All the subjects were also taking statin drugs.

The subjects were supplemented with 200 mg per day of oral CoQ10 or a placebo for 12 weeks. The researchers used ultrasound to evaluate endothelium dysfunction by measuring brachial artery flow-mediated dilatation, which shows the ability of the blood vessels to relax. They also measured nitrate-mediated dilatation, which is similar to the relaxation of the blood vessels that occurs when the body produces its own endothelium-derived relaxation factor nitric oxide. The researchers also measured levels of markers of systemic oxidative stress.

The results showed that CoQ10 supplementaion improved blood flow in the arm by 1 percent. This may potentially translate into a significant 10-25 percent reduction in cardiovascular risk. CoQ10 did not alter nitrate-mediated dilatation or markers of oxidative stress.

The study authors concluded, “CoQ10 supplementation improved endothelial dysfunction in statin-treated type 2 diabetic patients.”

Reference:

Hamilton SJ, Chew GT, Watts GF. Coenzyme C10 Improves Endothelial Dysfunction in Statin-Treated Type 2 Diabetic Patients. Diabetes Care. 2009 Feb 19. Published Online Ahead of Print.

Curcumin May Support Colon Health

Curcumin is the yellow pigment found in Curcuma longa (turmeric), historically used for anti-inflammatory properties. A recent study showed that curcumin may protect against ulcerative colitis in experimental models.

In this new study, experimental ulcerative colitis was induced in rats using a chemical called dextran sulfate sodium, which was added to their drinking water for 5 days. This chemical induced changes in the rats consistent with ulcerative colitis, such as ulcerations in inner lining of the colon, shrinkage of colon length, increased relative colon weight/length ratio, swelling and edema of the mucosal lining in the colon, and bloody stool. Additionally, measures of inflammation and oxidative stress were increased, including tumor necrosis factor alpha, colonic myleoperoxidase, malondialdehyde (MDA), and total nitric oxide. There were also decreased levels of the enzyme glutathione-S-transferase activity in the colon and reduced levels of the potent antioxidant glutathione, which is important for cell detoxification and reducing damage caused by lipid peroxidation.

When these rats received curcumin for 7 consecutive days prior to receiving the dextran sulfate sodium, these detrimental changes were mitigated. In fact, all of the damaging changes noted above were ameliorated in the animals given curcumin.

The study authors concluded, “These results suggest that curcumin could possibly have a protective role in ulcerative colitis probably via regulation of oxidant/antioxidant balance” as well as by modulating the release of inflammatory mediators.

Reference:

Arafa HM, Hemeida RA, El-Bahrawy AI, Hamada FM. Prophylactic role of curcumin in dextran sulfate sodium (DSS)-induced ulcerative colitis murine model. Food Chem Toxicol. 2009 Mar 11. Published Online Ahead of Print.

Researchers Discover Important Benefits of Tocotrienols

Tocotrienols, a specific form of vitamin E, may have interesting and significant new health benefits, according to a recent study.

Vitamin E occurs in 8 forms, including four tocopherols and four tocotrienols, designated as alpha, beta, gamma, and delta. In this study, researchers investigated the effects of gamma-tocotrienols and delta-tocotrienols on cancer growth. Liver cancer cells from mice were treated with both forms of tocotrienols in vitro. Additionally, mice were implanted with liver cancer cells and fed a diet supplemented with gamma and delta tocotrienols for 4 weeks.

During the in vitro part of the study, the delta-tocotrienol inhibited the growth of the cancer cells more strongly than gamma-tocotrienol by inducing programmed cell death, known as apoptosis. When the researchers conducted the in vivo part of the study, they found that in the mice implanted with the cancer cells, both forms of these two tocotrienols delayed the growth of the tumors. The delta- and gamma-tocotrienols did not significantly affect body weight nor normal tissue weight. Also, these two tocotrienols did not affect immunoglobulin levels, which indicate that these tocotrienol isomers did not act through modulation of the immune system.

The researchers concluded, “These results, to our knowledge, are the first demonstration of specific accumulation of gamma-tocotrienol and delta-tocotrienol in tumors and suggest that tocotrienol accumulation is critical for the anti-tumor activities of tocotrienols.”

Reference:

Hiura Y, Tachibana H, Arakawa R, Aoyama N, Okabe M, Sakai M, Yamada K. Specific accumulation of gamma- and delta-tocotrienols in tumor and their antitumor effect in vivo. J Nutr Biochem. 2008 Sep 26. Published Online Ahead of Print.

Annatto Tocotrienols is a particularly rich source of delta-tocotrienol.

Nutrient Found to Support Healthy Blood Pressure

Currently, it is estimated that one in three adults in the United States has hypertension. Hypertension, or high blood pressure,  is defined as an untreated blood pressure of 140/90 mmHg or higher, a patient taking anti-hypertensive medication, or at least two elevated blood pressure readings recorded by a health care professional.

In a recent clinical trial, researchers investigated the effects of supplementation with conjugated linoleic acid (CLA) in obese hypertensive subjects. In this double-blind, placebo-controlled study, 80 obese subjects with uncontrolled essential hypertension were given 4.5 grams per day CLA plus 37.5 mg per day of ramipril, or 37.5 mg per day ramipril plus placebo for 8 weeks. Ramipril is an anti-hypertensive medication that acts by inhibiting the angiotensin-converting enzyme (ACE inhibitor).

The study participants were evaluated for blood pressure, concentrations of plasma adiponectin, leptin, angiotensinogen, and ACE activity at the beginning and conclusion of the study. Adiponectin and leptin are adipocytokines, which are cell signaling molecules secreted from adipose tissue. Adiponectin is a hormone that decreases in concentration as body fat increases. Leptin is also a hormone and is important in appetite and metabolism regulation. Angiotensinogen is a pre-hormone that is secreted from the liver and is converted to angiotensin, a hormone that causes increased blood pressure.

The results showed that adding CLA to ramipril significantly enhanced the reduction effect of ramipril on both systolic and diastolic blood pressure. In addition, the CLA group had increased plasma adiponectin levels and decreased plasma levels of leptin and angiotensinogen.

The authors stated that “an 8-week long supplementation of CLA enhanced the effect of ramipril on blood pressure reduction in treated obese hypertensive patients. The anti-hypertensive effect of CLA might be related to the changed secretion of hypertensive adipocytokines in plasma.”

Reference:

Zhao WS, Zhai JJ, Wang YH, Xie PS, Yin XJ, Li LX, Cheng KL. Conjugated Linoleic Acid Supplementation Enhances Antihypertensive Effect of Ramipril in Chinese Patients With Obesity-Related Hypertension. Am J Hypertens. 2009 Mar 19. Published Online Ahead of Print.

Vitamin Supports Bone Health

A new study shows that consumption of an important nutrient is crucial for reducing the risk of fractures.

The risk of bone fractures increases with age as the bones weaken leading to osteopenia and osteoporosis. According to the National Health and Nutrition Examination Survey (NHANES), 56 percent of women 50 years of age and older and 87 percent among women 80 years of age and older have decreased bone density.

In a recently published review of the literature, data from numerous double-blind randomized controlled studies was pooled to investigate the relationship between oral vitamin D supplementation and prevention of non-vertebral and hip fractures among individuals 65 years or older.

This meta-analysis evaluated 12 clinical trials with 42,279 subjects for non-vertebral fractures and 8 clinical trials with 40,886 subjects for hip fractures and the relationship with oral vitamin D supplementation. The meta-analysis showed decreased relative risk of non-vertebral and hip fractures with oral vitamin D supplementation. More specifically, these results showed that vitamin D supplementation decreases non-vertebral fractures by 14 percent and the risk of hip fractures by 9 percent.

Additionally, the study showed that higher doses of vitamin D, above 400 IU per day, and higher blood 25-hydroxyvitamin D levels had an even more significant reduction in the risk of fracture. When the researchers analyzed the data from the nine studies that had provided supplementation over 400 IU per day, the data showed a 20 percent reduction in non-vertebral fractures and an 18 percent reduction in hip fractures. Also, the analysis revealed that higher doses of vitamin D decreased non-vertebral fractures in community-dwelling individuals by 29 percent and in institutionalized older individuals by 15 percent, and these results were independent of calcium supplementation.

The researchers concluded, “Non-vertebral fracture prevention with vitamin D is dose dependent, and a higher dose should reduce fractures by at least 20% for individuals aged 65 years or older.”

Reference:

Bischoff-Ferrari HA, Willett WC, Wong JB, Stuck AE, Staehelin HB, Orav EJ, Thoma A, Kiel DP, Henschkowski J. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med. 2009 Mar 23;169(6):551-61.

Nutrient Supports Cardiovascular Health

Elevated blood levels of triacylglycerol, also known as triglycerides, are associated with increased risk of atherosclerosis and heart disease, as well as type 2 diabetes and non-alcoholic fatty liver disease.

A recently published study examined the relationship between alpha-lipoic acid supplementation and triglyceride levels using an experimental rat model. Diabetic fatty rats were fed a regular diet supplemented with alpha-lipoic acid at a dose of 200 mg/kg body weight per day for 5 weeks.

The rats fed the standard diet developed elevated triglyceride levels in the blood (hypertriglyceridemia), while the rats supplemented with alpha-lipoic acid showed lower levels of triglycerides. The researchers showed that alpha-lipoic acid decreased liver and blood triglyceride levels by inhibiting the expression of specific genes in liver cells. These genes encode for the enzymes sn-glycerol-3-phosphate acyltransferase-1 and diacylglycerol O-acyltransferase-2, which are important enzymes in the formation of triglycerides and adipose (fat) tissue. By inhibiting these genes, the liver secreted less triglycerides into the circulation, and increased clearance of triglyceride-rich lipoproteins.

In addition, the livers from the rats supplemented with alpha-lipoic acid had increased glycogen, which is the storage form of glucose, suggesting that dietary carbohydrates were stored as glycogen instead of being used to produce lipids in the liver. Additionally, the researchers examined the activation of another gene important in lipid metabolism found in liver cells known as peroxisome proliferator activated receptor alpha (PPAR-alpha). PPAR-alpha was unchanged or decreased with lipoic acid supplementation, thus showing that the mechanism of triglyceride lowering by alpha-lipoic acid is unlike the mechanism of action of fibrate drugs, which are often prescribed to lower elevated lipids (hyperlipidemia) and are known activators of PPAR-alpha.

The study authors concluded, “Given its strong safety record, lipoic acid may have potential clinical applications for the treatment or prevention of hypertriglyceridemia and diabetic dyslipidemia.”

Reference:

Butler JA, Hagen TM, Moreau R. Lipoic acid improves hypertriglyceridemia by stimulating triacylglycerol clearance and downregulating liver triacylglycerol secretion. Arch Biochem Biophys. 2009 Feb 20. Published Online Ahead of Print.

Grape Polyphenols May Help Maintain a Healthy Weight

In a new study, the polyphenols found in grape seed extract were shown to modulate various biochemical pathways associated with obesity and reduced weight gain.

In this study, hamsters received either the standard diet, a high-fat diet, or a high-fat diet plus grape seed extract for 12 weeks. Abdominal fat and several biochemical parameters were measured including plasma glucose, triglycerides, insulin, leptin and adiponectin. Leptin is a hormone that plays a role in energy metabolism and appetite. Similarly, adiponectin is a hormone secreted from fat tissue that plays a role in obesity. Higher adiponectin levels are associated with a lower percentage of body fat.

The researchers also measured two markers of oxidative stress in the hamsters: cardiac production of superoxide anions and the expression of the enzyme NADPH oxidase.

The results showed that the hamsters fed the high-fat diet had increased abdominal fat compared to the hamsters fed the standard diet. Interestingly, the addition of grape seed extract to the high-fat diet mitigated the increased abdominal fat. In addition, the hamsters fed the high-fat diet had elevated levels of glucose, triglycerides, insulin, and greater insulin resistance values. Grape seed extract added to the high-fat diet also reduced these measurements. In fact, grape seed extract lowered blood glucose and insulin resistance values, reducing insulin by 16.5 percent. Grape seed extract also reduced leptin by 45 percent, and adiponectin levels increased by 61 percent, compared with obese controls. Also, grape seed extract inhibited measurements of oxidative stress, decreasing the production of cardiac superoxide by 74 percent and NADPH oxidase expression by 30 percent.

The study authors concluded, “chronic consumption of grape phenolics is shown to reduce obesity development and related metabolic pathways including adipokine secretion and oxidative stress.”

Reference:

Décordé K, Teissèdre PL, Sutra T, Ventura E, Cristol JP, Rouanet JM. Chardonnay grape seed procyanidin extract supplementation prevents high-fat diet-induced obesity in hamsters by improving adipokine imbalance and oxidative stress markers. Mol Nutr Food Res. 2008 Nov 26. Published Online Ahead of Print.

Vinpocetine May Improve Cerebrovascular Health

Cerebrovascular disorders are diseases caused by either alterations in blood flow to the brain or abnormalities in the blood vessels that supply the brain with blood. One of the causes of these disorders are abnormal rheological factors of the blood, which cause disturbances in the way that the blood flows through the arteries and veins. These abnormalities could be due to increased viscosity (thickness) or blood clots, which can predispose patients with chronic cerebrovascular disease to recurrent strokes.

In a recently published clinical trial, vinpocetine, derived from a constituent of periwinkle, was studied to determine if it has beneficial hemo-rheological properties, meaning improving the way the blood flows. In this study, 40 patients with chronic ischemic cardiovascular disease received gradually increasing dosages of intravenous vinpocetine. The patients also received either 30 mg vinpocetine orally or placebo for 3 months. Rheological factors of the blood including hematocrit, plasma fibrinogen, whole blood viscosity, red blood cell aggregation and deformability were evaluated after 1 month and 3 months of treatment.

The results showed that intravenous vinpocetine significantly decreased red blood cell aggregation, which lowered plasma and whole blood viscosity compared to the values measured at the beginning of the study, thereby improving blood flow. Also, the patients that received the additional oral vinpocetine had plasma and whole blood viscosities significantly lower than the patients in the placebo group after 3 months of treatment.

The authors concluded, “Our results confirmed the beneficial rheological effects of high-dose parenteral vinpocetine (partially caused by hemodilution) observed previously, and also warrant its long-term oral admission to maintain the beneficial rheological changes.”

Reference:

Feher G, Koltai K, Kesmarky G, Horvath B, Toth K, Komoly S, Szapary L.  Effect of parenteral or oral vinpocetine on the hemorheological parameters of patients with chronic cerebrovascular diseases.  Phytomedicine. 2009 Mar;16(2-3):111-7.

Vinpocetine is available here as a stand-alone supplement and also in the formula Extension IQ^™.

St. John’s Wort Studied in Perimenopausal Women

In a recently published study, a botanical long used for its ability to support mental health was shown to improve symptoms and reported quality of life in perimenopausal women.

In this study, 47 perimenopausal women aged 40 to 65 years who experience three or more hot flashes per day were supplemented with 900 mg three times per day of St. John’s wort (Hypericum perforatum) extract or a placebo for 3 months. The study subjects recorded symptoms in a daily diary for 1 week prior to the beginning of the study and for the week prior to the conclusion of the study.

The results showed that after 12 weeks, the women receiving St. John’s wort had significantly improved quality of life according to the Menopause-Specific Quality of Life questionnaire, and significantly reduced sleep problems. The hot flash frequency and hot flash score (frequency times severity) showed some improvement with St. John’s wort, although it did not reach statistical significance.

Thus, the authors stated that “Hypericum perforatum may improve quality of life in ways that are important to symptomatic perimenopausal women, but these results need to be confirmed by a larger clinical trial.”

Reference:

Al-Akoum M, Maunsell E, Verreault R, Provencher L, Otis H, Dodin S. Effects of Hypericum perforatum (St. John’s wort) on hot flashes and quality of life in perimenopausal women: a randomized pilot trial. Menopause. 2009 Feb 3. Published Online Ahead of Print.

St. John’s wort is found in the formulas Positrol^™ and SynCholamine^™.

Botanical May Improve Sleep Quality

According to the National Sleep Foundation, Restless Leg Syndrome (RLS) affects approximately 10 percent of adults in the United States. RLS is a neurological condition characterized by an unpleasant sensation in the legs, which causes difficulty initiating sleep and is relieved by movement of the legs.

In a recently published clinical trial, valerian (Valeriana officinalis) supplementation was evaluated in patients with RLS. In this prospective, triple-blinded, randomized, placebo-controlled study, 37 subjects with RLS aged 36 to 65 were given either 800 mg of valerian daily or a placebo for 8 weeks. The subjects were evaluated at the beginning of the study and after 8 weeks of treatment using the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and International RLS Symptom Severity Scale.

When the researchers looked at the entire group of subjects and compared them to the placebo, effects were similar. However, when the researchers compared the effects of 800 mg of valerian on the RLS subjects who did not suffer daytime sleepiness to valerian’s effects on the subjects who did suffer daytime sleepiness, there was a significant difference before and after valerian treatment in sleepiness and RLS symptoms. In fact, there was a strong positive association between reduced daytime sleepiness and reduced RLS symptom severity in the subjects given valerian.

The authors concluded that the “results of this study suggest that the use of 800 mg of valerian for 8 weeks improves symptoms of RLS and decreases daytime sleepiness in patients that report an Epworth Sleepiness Scale (ESS) score of 10 or greater. Valerian may be an alternative treatment for the symptom management of RLS with positive health outcomes and improved quality of life.”

Reference:

Cuellar NG, Ratcliffe SJ. Does valerian improve sleepiness and symptom severity in people with restless legs syndrome? Altern Ther Health Med. 2009 Mar-Apr;15(2):22-8.

Valerian is included in the formula Herbal Sleep, which also contains other sleep-supporting substances.

Since the day ephedra was taken off the market, suppliers have bombarded us with promises of an equally effective replacement. However, nothing that they sent us ever really worked. So, when our QC manager went on holiday to Brazil and brought back a case of Porangaba tea (also known as Chá de Bugre), we didn’t get too excited. We had already sampled many Chá De Bugre products and found them to be largely ineffective. This one, however, was different. For one thing, it was whole, unprocessed tea, not powdered herb or extract. Our President and Chief Science Officer both tried it and found that, with just one cup, their appetites were completely eliminated! Just a fluke? To find out, we shared our limited supply with more people in the office, and in a matter of weeks, one man had lost 11 lbs. and one woman 15 lbs. Everyone who tried Porangaba reported appetite-reducing benefits.

Although no published human trials have been conducted, centuries of tradition and anecdotal data have accumulated on Porangaba to support its appetite-suppressant and weight loss properties. The popularity of Porangaba increased dramatically when Dr. C.L. Cruz published his book Dictionary of the Plants Used in Brazil, where he reported in detail all the known health benefits of Porangaba tea. Among other uses, Dr. Cruz recommends Porangaba as a mild diuretic and a heart tonic that improves blood circulation.

Porangaba Tea from VRP is wildcrafted and unextracted, produced by a family-owned company with generations of experience in traditional tea and beverage manufacture. Only the finest quality Porangaba is selected, and is sustainably harvested in accordance with centuries of traditional Amazonian herb knowledge. Rigorous quality control ensures only the purest, highest quality Porangaba tea is approved for distribution. VRP is the exclusive North American distributor for this source of Porangaba.

For appetite-suppressing benefit, Porangaba works best 30 minutes before a meal. It gives the sense of being full after eating smaller amounts of food. It also appears to delay the emptying time of the stomach. Rather than completely suppressing hunger, like ephedra and amphetamines do, with a rebound hunger effect when they wear off, Porangaba reduces the amount of food intake to achieve satiety.

Researchers have long known that obesity is tied to an important cardiovascular disease risk factor known as endothelial dysfunction. This refers to dysfunction in the endothelium, the layer of cells lining the blood vessel walls. Disturbing new research, however, by Mayo Clinic researchers indicates that even small weight gain in lean, healthy adults can result in endothelial dysfunction, putting these otherwise healthy subjects at an increased risk for heart disease.

In this article, we will discuss the results of this new study and address a two-pronged approach that can be used for both weight management and maintaining healthy blood vessels. First, though, we will explain the importance of the endothelium in cardiovascular health.

Endothelial Dysfunction

Endothelial cells are the cells that line the blood vessels. When there is damage to the endothelium—the blood vessel lining that contains these cells—it can obstruct blood flow, leading to heart attacks and strokes.

The endothelium plays a crucial role in regulating vascular function and structure. In healthy conditions, nitric oxide produced by endothelial cells exerts not only vasodilating (blood vessel widening) properties, but also several other protective actions toward the vessel wall against the development of atherosclerosis and thrombosis. Traditional cardiovascular risk factors are characterized by endothelial dysfunction caused by an enhanced production of oxidative stress that reduces the availability of nitric oxide.1

Endothelial dysfunction represents the earliest abnormality in the development of vascular disease. It is linked to subsequent atherosclerosis progression and cardiovascular disease events.2

Arterial endothelial dysfunction occurs at all stages of atherosclerosis, both preceding structural atherosclerosis changes, as well as before cardiac events in late obstructive disease. Thus, the link between endothelial dysfunction and risks of vascular events such as heart attacks and strokes is well established.3

Endothelial dysfunction plays a central and critical role in other aspects of cardiovascular disease including the initiation and development of idiopathic pulmonary arterial hypertension (IPAH) and angina.4-5

Endothelial dysfunction is thought to play an important part in the increased risk of heart disease in rheumatoid arthritis patients6 and may explain the high prevalence of cardiovascular disease found in people with the metabolic syndrome and diabetes.2

In human subjects, researchers usually measure endothelial function by measuring what’s known as flow mediated dilatation, a technique that is less invasive than other possible ways to measure endothelial function. Tracking flow mediated dilatation is a non invasive ultrasound-based method that researchers can use to measure arterial diameter and blood flow in the vessels.3

Minor Weight Gain Increases Heart Disease Risk

For many years researchers have investigated how obesity can wreak havoc on the endothelium. However, a new study indicates that it doesn’t take a lot of weight gain—as little as 9 pounds of visceral fat in lean, healthy subjects—to cause endothelial dysfunction and increase the risk of heart disease.

Mayo clinic researchers conducted a randomized, blinded, controlled trial to investigate how weight gain and subsequent weight loss affected endothelial function. The study authors recruited 43 lean, healthy volunteers (average age 29 years) who each had a body mass index of between 18.5 and 24.9 kilograms. Forty-two percent of the subjects were women. All subjects were non-smokers and none were on medications. After a weight maintenance period supervised by an experienced dietitian, volunteers randomly were assigned into a group of 35 people who gained weight (about 9 pounds) or a group of eight subjects who maintained their weight.

The scientists measured endothelial function in the subjects by determining flow mediated dilatation in the brachial artery, a large vessel in the upper arm. The measurements were always taken at the same time each day, in the early morning. In the weight gain group, researchers measured endothelial dysfunction at the study’s start, after the subjects gained fat at 8 weeks, and after weight loss at 16 weeks. In subjects who maintained their weight, endothelial function was measured at the study’s start and at 8 weeks. Low flow indicated vessel dysfunction.

At the conclusion of the study, the subjects who had gained an average of 9 pounds experienced a significant increase in their visceral fat (the abdominal fat surrounding internal organs) and subcutaneous fat found just under the skin. In these subjects, the brachial artery flow measurements decreased as weight was gained. The endothelial dysfunction noted in these subjects appeared to be related to a specific type of weight gain, notably visceral fat gain rather than subcutaneous fat gain. Once the weight was lost, endothelial function was restored to levels measured at the beginning of the study.

In the group who maintained their weight, endothelial function remained unchanged.7

According to the Mayo Clinic researchers who conducted the study, “In lean healthy young subjects, modest weight gain results in impaired endothelial function, even in the absence of changes in blood pressure. Endothelial function recovers after weight loss. Visceral rather than subcutaneous fat predicts endothelial dysfunction.”

This study sheds new light on the small amount of weight gain that many individuals consider to be a normal part of aging.

Weight Loss and Healthy Blood Vessels

Since the individuals in the above study were able to restore the health of their blood vessels once they lost the weight, the first step in maintaining cardiovascular health would be to shed even small amounts of weight gain.

One of the easiest ways to reduce weight and control appetite is to consume porangaba tea. Consuming whole, unprocessed porangaba tea has been found to reduce appetite and produce up to 15 pounds of weight loss in a matter of weeks.

Centuries of tradition and anecdotal data have accumulated on Porangaba to support its appetite-suppressant and weight loss properties. The popularity of Porangaba increased dramatically when Dr. C.L. Cruz published his book Dictionary of the Plants Used in Brazil, in which he reported in detail all the known health benefits of Porangaba tea. Among other uses, Dr. Cruz recommends Porangaba as a weight loss aid, a mild diuretic and a heart tonic that improves blood circulation.

For appetite-suppressing benefit, Porangaba works best when taken 30 minutes before a meal. It gives the sense of being full after eating smaller amounts of food. It also appears to delay the emptying time of the stomach. Rather than completely suppressing hunger, like ephedra and amphetamines do, with a rebound hunger effect when they wear off, Porangaba reduces the amount of food intake to achieve satiety.

Strengthening Blood Vessels

An effective two-part approach to improving cardiovascular health must go beyond weight loss and also restore endothelial function. Fucoidan—a sulfated polysaccharide extracted from brown seaweed—is now thought to have a role to play in endothelial repair by virtue of its ability to increase the activity of stem cells that repair cardiovascular damage. Studies have begun to emerge indicating fucoidan might influence the mobilization of endothelial stem cells and their incorporation into ischemic tissue. By mobilizing the endothelial cells to sites of blood vessel damage, fucoidan can strengthen the vessels and improve cardiovascular health.8

Recent studies suggest that fucoidan may work by enhancing the activity of stromal-derived factor 1 (SDF-1), which plays a critical role at several steps of progenitor (stem) cell mobilization. Researchers reporting in the journal Blood recently discovered that plasma concentrations of the highly potent SDF-1 increased rapidly and dramatically after treatment with fucoidan in monkeys and in mice, coinciding with decreased levels in bone marrow. In vitro and in vivo data suggest that fucoidan displaces certain factors that normally trap the SDF-1 in bone marrow, on endothelial cell surfaces or other tissues, helping to release the SDF-1 and allowing it to more easily mobilize the stem cells. The researchers tested other mobilizing agents to see if they would have the same effect but fucoidan was the only substance tested able to increase SDF-1 activity and enhance stem cell mobilization to sites of injury.9

Numerous in vitro and animal studies have shown that fucoidan can strengthen the blood vessels by interacting with endothelial cells, producing anticoagulant effects. Studies have shown that fucoidan inhibits vascular smooth muscle cell growth to the same extent as heparin and that it can help endothelial cells migrate to the site of blood vessel injuries. Fucoidan has been shown to act in the same way as heparin with a mechanism of action that involves regulating tissue factor pathway inhibitor (TFPI), a process that is involved in blood coagulation. Fucoidan causes the endothelium to release TFPI, resulting in anti-coagulant effects.10

The results of these studies led researchers to conclude, “Moreover, the data already suggest a potential role of fucoidan as a new therapeutic agent of vegetal origin in the vascular endothelium wound repair.”11

Conclusion

The surprising new study by Mayo Clinic researchers indicated that lean subjects who gain even a small amount of weight could suffer blood vessel damage. Therefore, individuals who want to maximize their heart-protection supplement regimens can focus on weight loss goals by consuming porangaba tea and improving the health of the endothelium with fucoidan.  Furthermore, consuming a good multivitamin and/or antioxidant supplement can provide synergistic support as substantial research exists to show that vitamins C as well as other antioxidants can inhibit the free radical damage and other factors involved in endothelial dysfunction.

References

1. Taddei S, Ghiadoni L, Salvetti G, Virdis A, Salvetti A. [Obesity and endothelial dysfunction]. [Article in Italian]. G Ital Cardiol (Rome). 2006 Nov;7(11):715-23.
2. Meyers MR, Gokce N. Endothelial dysfunction in obesity: etiological role in atherosclerosis. Curr Opin Endocrinol Diabetes Obes. 2007 Oct;14(5):365-9.
3. Patel S, Celermajer DS. Assessment of vascular disease using arterial flow mediated dilatation. Pharmacol Rep. 2006;58 Suppl:3-7.
4. Junhui Z, Xingxiang W, Guosheng F, Yunpeng S, Furong Z, Junzhu C. Reduced number and activity of circulating endothelial progenitor cells in patients with idiopathic pulmonary arterial hypertension. Respir Med. 2008 Apr 2. [Epub ahead of print].
5. Li AH, Lee BC, Chen KC, Weng CS, Chu SH. Brachial Artery Flow-Mediated Vasodilation in Patients With Cardiac Syndrome X. Angiology. 2008 Apr 2. [Epub ahead of print].
6. Rojas-Villarraga A, Ortega-Hernandez OD, Gomez LF, Pardo AL, López-Guzmán S, Arango-Ferreira C, Hincapie ME, Betancur JF, Pineda-Tamayo R, Diaz FJ, Anaya JM. Risk Factors Associated with Different Stages of Atherosclerosis in Colombian Patients with Rheumatoid Arthritis. Semin Arthritis Rheum. 2008 Apr 4. [Epub ahead of print].
7. Corral AR, Sierra-Johnson J, Orban M, Gami AS, Kuniyoshi FHS, Pusalavidyasager S, Davison D, Huyber CM, Votruba SM, Jensen MD, Somers VK. Modest Fat Gain Causes Endothelial Dysfunction In Lean Healthy Humans: A Randomized Blinded Controlled Trial. Circulation. 2007;116:I6 Supplement:797.
8. Boisson-Vidal C, Zemani F, Caligiuri G, Galy-Fauroux I, Colliec-Jouault S, Helley D, Fischer AM. Neoangiogenesis induced by progenitor endothelial cells: effect of fucoidan from marine algae. Cardiovasc Hematol Agents Med Chem. 2007 Jan;5(1):67-77.
9. Sweeney EA, Lortat-Jacob H, Priestley GV, Nakamoto B, Papayannopoulou T. Sulfated polysaccharides increase plasma levels of SDF-1 in monkeys and mice: involvement in mobilization of stem/progenitor cells. Blood. 2002 Jan 1;99(1):44-51.
10. Giraux JL, Tapon-Bretaudière J, Matou S, Fischer AM. Fucoidan, as heparin, induces tissue factor pathway inhibitor release from cultured human endothelial cells. Thromb Haemost. 1998 Oct;80(4):692-5.
11. Giraux JL, Matou S, Bros A, Tapon-Bretaudière J, Letourneur D, Fischer AM. Modulation of human endothelial cell proliferation and migration by fucoidan and heparin. Eur J Cell Biol. 1998 Dec;77(4):352-9.