• The President’s Desk  — New Year, Old Battle

• New Year’s Weight Loss  — Study Confirms Abdominal Fat is Deadly Even in Normal Weight People

• Brain Health and Blood Sugar  — Is Alzheimer’s the New Type 3 Diabetes?

• New Product Announcements  — 

• Fatigue-Fighting Nutrients  — Enhancing Energy Levels Through Mitochondrial Support

• The Heart-Damaging Effects of Stress  — Controlling Cortisol for a Healthier Cardiovascular System

• Gastrointestinal Support  — Proactive Steps to Strengthen GI Health

• Pet Corner  — Optimal Doses of Pet Supplements

• Nutrition Review  — The Latest Research on Fatigue, Heart Health, Cognitive Function and More

• Restoring Intestinal Bacteria
• Itching and Depression
• Anxiety and Stress
• Heart Health, Diabetes
• Healthy Cholesterol Levels
• Scleroderma
• Hypoglycemia
• Kidney Health
• Pain
• Warts on Legs
• Stroke Recovery
• Heartburn

Although we’ve embarked upon a new year, one thing remains the same—the media’s inaccurate attack on vitamins. The latest assault was from The New York Times, in an article titled, “News Keeps Getting Worse for Vitamins.” Columnist Tara Parker-Pope writes, “The best efforts of the scientific community to prove the health benefits of vitamins keep falling short.” She then highlights a handful of negative studies about various vitamins.

One of those studies mentioned in the column was a recently published report that concluded neither vitamin E nor C could reduce the risk of major cardiovascular events in male physicians. In addition, subjects who took vitamin E experienced a 74 percent increased risk of hemorrhagic stroke. (JAMA. 2008 Nov 12;300(18):2123-33.)

Pope, however, neglected to quote anyone who could point out flaws in this or any study mentioned in her article. The above study was impressively large and was an eight-year follow up of a ten-year study, but it was riddled with holes. First, in the placebo group, 23 subjects suffered hemorrhagic stroke and in the vitamin E group 39 suffered strokes. That is a 74 percent increased risk, but it’s statistically insignificant in a study of 14,641 subjects. Second, the study used alpha-tocopherol, a synthetic form of vitamin E considerably less effective than mixed tocopherols. Furthermore, the subjects were instructed to consume a 400 IU vitamin E supplement only every other day!

The fault, of course, isn’t entirely the media’s. Scientists need to pay attention to the trial’s structure. In a recent study, ginkgo biloba extract was not effective in preventing dementia in older adults. However, the study included subjects in their late seventies who are at greater risk of developing Alzheimer’s and who may already be experiencing disease progression. It did not investigate middle-aged subjects where prevention could best be analyzed.

Thousands of studies have reported upon the beneficial effects of various vitamins, minerals, and botanicals. Funny, though, how negative, flawed studies capture the most attention while the positive ones get shoved into the background.

Often, weight loss gets put on the back burner until the holidays are over. And when individuals do commit to a weight loss program in January, they concentrate on subtracting pounds from their total, overall weight. Although this is a worthwhile goal, the newest research is showing that this approach may be shortsighted. As one of the newest and most alarming studies demonstrated, abdominal fat may be a stronger predictor of premature death than overall weight. At a time of year when everyone’s mind is on weight loss, I thought it would be particularly appropriate to discuss the findings of this new study and explain an effective approach to reduce the visceral fat that accumulates around abdominal organs.

Ticking Time Bomb in Our Abdomens

Many of the past studies investigating the association between weight and risk of death have relied upon the body-mass index of the subjects. The BMI uses a person’s height and weight to calculate a score. Individuals who have a BMI of between 25 and 29.9 points are considered overweight; anyone with a higher score is considered obese. According to current treatment guidelines, physicians usually only measure patients’ waists if their patients’ BMI indicates they are overweight.

In the past, most studies on weight gain and risk of death depended upon the BMI, but few studies examined whether the distribution of body fat contributes to the prediction of death. Now, however, an emerging body of evidence is finding that it’s not how many pounds a person gains but rather where the weight settles.

The newest study to reach this conclusion was one of the largest of its kind. Published in the New England Journal of Medicine, the study examined the association of BMI, waist circumference, and waist-to-hip ratio with the risk of death among 359,387 participants from nine countries. The subjects were taking part in the European Prospective Investigation into Cancer and Nutrition (EPIC) trial and ranged in age from 25 to 70. Researchers divided participants into groups according to their BMI, waist circumference and waist-to-hip ratio. In nearly ten years of follow-up, more than 14,723 subjects died from various causes.

The results indicated that participants with large waists had an increased risk of death—even if they were considered to be normal weight based upon their BMI. Normal-weight males whose waists measured about 40 inches or more had double the risk of dying compared to those who had waists 34 inches or less. Females whose BMI was normal but who had waists 35 inches or more had a 79 percent increased chance of dying compared to female subjects whose waists were 28 inches or less.

Another finding of the study was that for every five-centimeter (about two inches) increase in waist size in subjects with any BMI score, death risk rose by 17 percent for males and 13 percent for females. Comparing waist-to-hip ratios resulted in similar findings.¹

The researchers didn’t study why waist size increases the risk of death, but they theorize that the cause is likely visceral fat. Abdominal fat is usually visceral fat, which accumulates around organs and contributes to the development of the metabolic syndrome and heart disease.

Earlier in 2008, another study was published in the journal Circulation that reached a similar conclusion. In this study, scientists studied 44,636 women participating in the Nurses’ Health Study, to determine if there was an association between abdominal adiposity and all-cause and cause-specific mortality. During 16 years of follow-up, 3,507 deaths occurred, including 751 cardiovascular deaths and 1,748 cancer deaths. The researchers found that among normal-weight women (body mass index 18.5 to greater than 25 kg/m(2)), abdominal obesity was significantly associated with elevated cardiovascular disease mortality. Abdominal obesity also was strongly linked to death from cancer and other causes.²

The study authors concluded, “Measures of abdominal adiposity were strongly and positively associated with all-cause, CVD [cardiovascular disease], and cancer mortality independently of body mass index. Elevated waist circumference was associated with significantly increased CVD mortality even among normal-weight women.”

Abdominal Fat 101

In past issues of Vitamin Research News, we’ve discussed abdominal fat. Here is a reminder of why this type of fat is so dangerous to cardiovascular and overall health. Abdominal fat is actually comprised of: 1) subcutaneous fat, which accumulates under the skin and is relatively benign and 2) dense visceral fat, found deep in the abdomen, surrounding the intra-abdominal organs. Elevated levels of visceral fat causes metabolic syndrome and visceral fat cells release inflammatory cytokines such as C-reactive protein (CRP) and Interleukin (IL)-6, which contribute to chronic systemic inflammation. Visceral fat also can trigger increases in blood pressure due to the production of angiotensin, a chemical messenger that can cause the constriction of blood vessels. Even modest increases in visceral fat result in measurable endothelial dysfunction. Aging, excessive calorie intake and sedentary lifestyle all contribute to weight gain and visceral fat accumulation

Lose the Visceral Fat, Gain Longevity

Due to visceral fat’s destructive role, an important part of a New Year’s weight loss plan is abdominal fat reduction. In my clinical practice, I have found that the easiest way to accomplish this goal is with the supplement known as Glabrinex™. In both animal and human published studies, Glabrinex has demonstrated the ability to inhibit the formation of visceral fat as well as body fat as a whole. This supplement contains a proprietary lipid-soluble extract of Glycyrrhiza glabra L root, standardized for bioactive polyphenol flavonoid compounds and the unique flavonoid glabridin. Glabrinex has been shown in clinical trials to reduce body weight, waist circumference and abdominal fat, and to help control blood glucose.

Glabrinex is able to suppress visceral fat, thereby helping to eliminate a significant cause of metabolic syndrome. Glabrinex down-regulates the body’s fat-forming processes and up-regulates the activity of fat burning enzymes. Glabrinex reduces the weight gain produced by a high-fat diet and helps to control blood glucose.

In human randomized, double-blind, placebo-controlled studies, subjects experienced a reduction in body and abdominal fat after taking Glabrinex. They also experienced suppressed body weight gain.^3-4In recent animal studies using Glabrinex, abdominal fat accumulation, increased blood glucose levels and body weight gain were suppressed in obese diabetic mice and high-fat-diet-induced obese mice.^5-6,

Conclusion

The evidence continues to pour in that visceral fat—the dense fat found surrounding intra-abdominal organs—not only is unsightly but also is dangerous to our health. Studies show that this type of fat is linked to the metabolic syndrome, cardiovascular disease and premature death. Therefore, consuming a supplement such as Glabrinex is an ideal way to embark upon a New Year’s weight loss program and is an important part of any regimen designed to support healthy aging.

References

1. Pischon T, Boeing H, Hoffmann K, Bergmann M, Schulze MB, Overvad K, van der Schouw YT, Spencer E, Moons KGM, Tjønneland A, Halkjaer J, and Jensen MK, et al. General and Abdominal Adiposity and Risk of Death in Europe. New England Journal of Medicine. November 13, 2008;359(20):2105-2120. Sc.M.

2. Zhang C, Rexrode KM, van Dam RM, Li TY, Hu FB. Circulation. 2008 Apr 1;117(13):1658-67. Abdominal obesity and the risk of all-cause, cardiovascular, and cancer mortality: sixteen years of follow-up in US women.

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

4. Aoki F, Nakagawa K, Kitano M, Ikematsu H, Nakamura K, Yokota S, Tominaga Y, Arai N, Mae T. Clinical safety of licorice flavonoid oil (LFO) and pharmacokinetics of glabridin in healthy humans. J Am Coll Nutr. 2007 Jun;26(3):209-18.

5. Nakagawa K, Kishida H, Arai N, Nishiyama T, Mae T. Licorice flavonoids suppress abdominal fat accumulation and increase in blood glucose level in obese diabetic KK-A(y) mice. Biol Pharm Bull. 2004 Nov;27(11):1775-8.

6. Aoki F, Honda S, Kishida H, Kitano M, Arai N, Tanaka H, Yokota S, Nakagawa K, Asakura T, Nakai Y, Mae T. Suppression by licorice flavonoids of abdominal fat accumulation and body weight gain in high-fat diet-induced obese C57BL/6J mice. Biosci Biotechnol Biochem. 2007 Jan;71(1):206-14.

In the past, Alzheimer’s disease and diabetes were considered two unrelated conditions. However, scientists are discovering alarming similarities between type 2 diabetes and cognitive decline, adding dementia to the list of major concerns diabetics already face, including heart disease, strokes, kidney failure, and blindness.

Several large studies have found that people with type 2 diabetes are twice as likely to develop Alzheimer’s compared with healthy people of the same age and sex.1-2 Even more worrisome is that people with borderline diabetes, which affects a large part of the US population, are also at risk. A recent study found that 70 percent of elderly people with chronically elevated levels of blood glucose were more likely than those with normal levels to develop Alzheimer’s.³

The researchers concluded, “our findings highlight the need to detect borderline diabetes in order to proactively address both type 2 diabetes and dementia.”³

Scientists have also discovered that once Alzheimer’s is diagnosed, people with type 2 diabetes are twice as likely to die sooner than those without diabetes.⁴ As evidence for a link between the two diseases continues to mount, researchers are uncovering a number of reasons to explain the possible connection.

Poor Insulin and Glucose Control

Insulin resistance is a hallmark of type 2 diabetes and occurs when the body cannot properly use insulin, the hormone that is secreted by the pancreas to move glucose from the blood into cells that need it. In people on their way to type 2 diabetes, the pancreas produces extra insulin in a futile attempt to compensate. However, this only leads to higher insulin and glucose levels in the blood and a deficiency of glucose in the cells that need sugar to function properly, particularly brain cells, setting the stage for the development of Alzheimer’s. Scientists also believe that diabetes impacts memory via another mechanism: by increasing the risk blood vessels will become obstructed, restricting blood flow to the brain.

In addition, the recent discovery that insulin receptors are expressed in the hippocampus of the brain, which is crucial for learning and memory formation, has added further weight to the link with diabetes. When insulin becomes less able to bind to its receptors in the brain, the mechanisms for nerve-cell survival and memory formation also become affected, increasing the risk for Alzheimer’s.⁵

Toxic Byproducts of Excess Glucose

High blood glucose levels also impact cognition through the formation of sugar-related toxins called advanced glycation end products (AGEs). Anyone who has made toast has witnessed glycation firsthand, as reactions between sugars and proteins in the bread cause it to turn brown when heated. Similarly, in the body, glycotoxins are formed when sugars interact with proteins and lipids, damaging the structure of proteins and membranes, rendering them less able to carry out their many vital processes. These toxic AGE molecules are a critically important factor linking aging, diabetes, and Alzheimer’s.

In diabetes, AGEs play a pathologic role in damaging blood vessels and contribute to the micro- and macrovascular complications of the disease. They also contribute to degenerative processes in the brain. Laboratory studies show that AGEs are a key factor involved in the cross-linking of harmful beta-amyloid plaques in the brain that are implicated in Alzheimer’s.⁶

AGEs have also been found to accumulate in brain regions associated with memory and attention, areas also affected in Alzheimer’s.⁷ A recent study in approximately 200 healthy people aged over 70 found that those with the highest AGE levels performed significantly worse on six different tests of memory and cognitive ability than those with low levels.⁸

Promoting Healthy Blood Glucose Metabolism

Even those who pay careful attention to what they eat may find their blood glucose levels increase with age. Fortunately, combating high blood glucose levels and insulin resistance will help to maintain cognitive health. In addition to exercise and avoiding high-glycemic foods, certain natural substances may help maintain healthy blood glucose levels and prevent insulin spikes as well as quell the damage wrought by glycation.

N-Acetyl cysteine (NAC): A precursor of the tripeptide antioxidant glutathione, NAC protects pancreatic insulin-producing cells against damage from free radicals, which flourish in the presence of high glucose levels. NAC also inhibits the activation of a key proinflammatory molecule called nuclear factor-kappa beta.⁹ In addition, animal studies show that NAC inhibits the blood glucose surge and weight gain that occurs after consuming a sucrose-rich diet,¹⁰ while also protecting against oxidative stress, a major factor in diabetic complications.

Vitamin C: According to a large study of nearly 6,500 people aged 45-74 years, a vitamin C deficiency increased HbA1c, a measure of long-term blood sugar control that indicates how much glycation is occurring in the body. This study found that plasma vitamin C levels were significantly higher in subjects with HbA1c less than 7 percent compared with those whose HbA1c levels were 7 percent or more. The researchers concluded, “dietary measures to increase plasma vitamin C may be an important health strategy for reducing the prevalence of diabetes.”¹¹

Human studies have demonstrated that vitamin C supplements may help lower blood glucose levels in diabetics. Vitamin C may also produce additional reductions in low-density lipoprotein (LDL) and plasma free radicals.¹² A recent study of nearly 22,000 non-diabetic patients found that those whose plasma vitamin C levels were in the top 20 percent had a 62 percent lower risk of developing diabetes than those in the lowest fifth.¹³ Vitamin C also inhibits sorbitol accumulation and glycation of proteins that cause diabetic complications.

Vitamin E: An antioxidant that modulates insulin action and improves glucose transport,¹⁴ vitamin E is important in reducing long-term diabetic complications. Studies also have shown that diets rich in vitamin E significantly decrease the rate of mental decline and may help lower Alzheimer’s risk in some people.¹⁵ An effective approach is to combine vitamins C and E, which provides more complete protection against molecular damage.¹⁵

Goat’s Rue: This natural extract is rich in aminoguanidine, which helps to maintain healthy blood glucose levels. Goat’s rue improves insulin sensitivity and stabilizes blood sugar in both normal and diabetic humans¹⁶ as well as exerts anti-AGE effects.

Cinnamon: In a recent trial, cinnamon was found to help diminish the blood glucose spike that typically follows a meal, partly by delaying gastric emptying.¹⁷ In another study, daily consumption of 1-6 grams of the spice for 40 days reduced fasting serum glucose levels by 18-29 percent in people with type 2 diabetes.¹⁸ It is believed that cinnamon’s water-soluble polyphenols are responsible for its metabolic effects. Research shows that these natural compounds upregulate the expression of genes involved in activating insulin receptors on the cell membranes, increasing cellular glucose uptake and lowering blood glucose levels.¹⁹

Quercetin: This bioflavonoid strongly inhibits aldose reductase, an enzyme that converts glucose into sorbitol, which is implicated in diabetic complications. Quercetin also protects insulin-producing cells in the pancreas by blocking the genetic expression of cytokines and enzymes that are important mediators of inflammatory responses.²⁰

Vanadium: Vanadyl sulfate is a trace mineral that functions as an insulin-mimetic, improving glucose tolerance in type 2 diabetics and decreasing insulin requirements.²¹ A study of vanadyl sulfate treatment in type 2 diabetes found that a daily 150-mg dose for six weeks reduced blood glucose and HbA1c, while improving performance during an oral glucose tolerance test, which measures the body’s ability to metabolize glucose.²²

Bitter melon: This tropical fruit lowers blood glucose without raising insulin levels. In one study, an extract from bitter melon significantly improved glucose tolerance in 73 percent of 18 patients with type 2 diabetes.²³
Combining a supplement that contains all of the above ingredients (such as GluControl™) with a chromium supplement can be an ideal way to support healthy blood sugar levels and cognitive health.

AGE-Blocking Nutrients

Carnosine: This dipeptide comprised of beta-alanine and histidine binds to other protein molecules in the body, shielding them against glycation. Carnosine also protects neuronal cells from many of the pathologies implicated in Alzheimer’s disease, such as amyloid-beta peptide toxicity²⁴ and lipid peroxidation of neuronal membranes in the brain.²⁵

Vitamin B1 (thiamine) and benfotiamine: Benfotiamine is the highly bioavailable form of vitamin B1 that prevents nerve and blood vessel damage caused by glycation processes in diabetes. It works by blocking the accumulation of glycotoxins before they can do damage. Recent studies have shown that benfotiamine may reduce the threat of diabetic complications by suppressing the effects of AGEs²⁶ and significantly improving neuropathy scores in those with painful peripheral neuropathy.²⁷

Vitamin B6: Pyridoxine (vitamin B6) is converted to several active metabolites in the body, such as pyridoxamine and pyridoxal-5-phosphate, which react with key intermediates involved in glycation and suppress the formation of AGEs. Pyridoxamine has also been shown in human studies to help avert diabetic complications.²⁸

NAC: is also a natural potent AGE inhibitor shown to reduce lipid peroxidation in neuronal cell lines after AGE exposure. These impressive findings have led researchers to conclude that NAC could be useful in protecting brain tissue from the pathophysiological consequences characteristic of Alzheimer’s.²⁹

Two other emerging, powerful AGE-blocking agents are Guava and Yerba maté. Abundant polyphenols found in both of these plant extracts are believed to be responsible for their significant and dose-dependent inhibitory effect on the glycation of lipids and proteins.^30-31
Using a supplement that combines each of these ingredients (such as AGEBlock®) can play an important role in inhibiting AGEs and thus enhancing cognitive health.

Conclusion

Diabetes and Alzheimer’s are two epidemic disorders that share an extraordinary number of biochemical similarities; each disease is poised to threaten the health of tens of millions of Americans. Even people who watch what they eat may experience accumulated damage from glycation in tissues exposed to normal blood sugar for a long enough time. Fortunately, an integrated program comprising an anti-glycation eating plan, exercise, and scientifically validated nutrients combats several insidious factors that can help ward off the related afflictions of diabetes and Alzheimer’s.

References

1. Ott A, Stolk RP, van Harskamp F, Pols HA, Hofman A, Breteler MM. Diabetes mellitus and the risk of dementia: The Rotterdam Study. Neurology. 1999 Dec 10;53(9):1937-42.

2. Arvanitakis Z, Wilson RS, Bienias JL, Evans DA, Bennett DA. Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. Arch Neurol. 2004 May;61(5):661-6.

3. Xu W, Qiu C, Winblad B, Fratiglioni L. The effect of borderline diabetes on the risk of dementia and Alzheimer’s disease. Diabetes. 2007 Jan;56(1):211-6.

4. Helzner EP, Scarmeas N, Cosentino S, Tang MX, Schupf N, Stern Y. Survival in Alzheimer disease: a multiethnic, population-based study of incident cases. Neurology. 2008 Nov 4;71(19):1489-95.

5. Zhao W, De Felice FG, Fernandez S, et al. Amyloid beta oligomers induce impairment of neuronal insulin receptors. FASEB J. 2008;22:246-60.

6. Münch G, Kuhla B, Lüth HJ, Arendt T, Robinson SR. Anti-AGEing defences against Alzheimer’s disease. Biochem Soc Trans. 2003 Dec;31(Pt 6):1397-9.

7. Takeuchi M, Kikuchi S, Sasaki N, et al. Involvement of advanced glycation end-products (AGEs) in Alzheimer’s disease. Curr Alzheimer Res. 2004 Feb;1(1):39-46.

8. Beeri MS. Advanced Glycation Is Associated with Cognitive Impairment in Very Old Women. Paper Presented to the 10th International Conference on Alzheimer’s Disease and Related Disorders in Madrid. 2006.

9. Ho E, Chen G, Bray TM. Supplementation of N-acetylcysteine inhibits NFkappaB activation and protects against alloxan-induced diabetes in CD-1 mice. FASEB J. 1999; 13(13):1845-54.

10. Diniz YS, Rocha KK, Souza GA, et al. Effects of N-acetylcysteine on sucrose-rich diet-induced hyperglycaemia, dyslipidemia and oxidative stress in rats. Eur J Pharmacol. 2006 Aug 14;543(1-3):151-7.

11. Sargeant LA, Wareham NJ, Bingham S, et al. Vitamin C and hyperglycemia in the European Prospective Investigation into Cancer--Norfolk (EPIC-Norfolk) study: a population-based study. Diabetes Care. 2000 Jun;23(6):726-32.

12. Afkhami-Ardekani M, Shojaoddiny-Ardekani A. Effect of vitamin C on blood glucose, serum lipids & serum insulin in type 2 diabetes patients. Indian J Med Res. 2007 Nov;126(5):471-4.

13. Harding AH, Wareham NJ, Bingham SA, et al. Plasma vitamin C level, fruit and vegetable consumption, and the risk of new-onset type 2 diabetes mellitus: the European prospective investigation of cancer—Norfolk prospective study. Arch Intern Med. 2008 Jul 28;168(14):1493-9.

14. Paolisso G, D’Amore A, Giugliano D, Ceriello A, Varricchio M, D’Onofrio F. Pharmacologic doses of vitamin E improve insulin action in healthy subjects and non-insulin-dependent diabetic patients. Am J Clin Nutr. 1993 May;57(5):650-6.

15. Foley DJ, White LR. Dietary intake of antioxidants and risk of Alzheimer disease: food for thought. JAMA. 2002;287(24):3261-3.

16. Petricic J, Kalodera Z. Galegin in the goats rue herb: its toxicity, antidiabetic activity and content determination. Acta Pharm Jugosl. 1982;32(3):219-23.

17. Hlebowicz J, Darwiche G, Björgell O, Almér LO. Effect of cinnamon on postprandial blood glucose, gastric emptying, and satiety in healthy subjects. Am J Clin Nutr. 2007 Jun;85(6):1552-6.

18. Khan A, Safdar M, Ali Khan MM, Khattak KN, Anderson RA. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care. 2003 Dec;26(12):3215-8.

19. Imparl-Radosevich J, Deas S, Polansky MM, et al. Regulation of PTP-1 and insulin receptor kinase by fractions from cinnamon: implications for cinnamon regulation of insulin signaling. Horm Res. 1998 Sep;50(3):177-82.

20. Zunino SJ, Storms DH, Stephensen CB. Diets rich in polyphenols and vitamin A inhibit the development of type I autoimmune diabetes in nonobese diabetic mice. J Nutr. 2007 May;137(5):1216-21

21. Poucheret P, Verma S, Grynpas MD, McNeill JH. Vanadium and diabetes. Mol Cell Biochem. 1998 Nov;188(1-2):73-80.

22. Cusi K, Cukier S, DeFronzo RA, Torres M, Puchulu FM, Redondo JC. Vanadyl sulfate improves hepatic and muscle insulin sensitivity in type 2 diabetes. J Clin Endocrinol Metab. 2001 Mar;86(3):1410-7.

23. Welihinda J, Karunanayake EH, Sheriff MH, Jayasinghe KS. Effect of Momordica charantia on the glucose tolerance in maturity onset diabetes. J Ethnopharmacol. 1986 Sep;17(3):277-82.

24. Hipkiss AR. Could carnosine or related structures suppress Alzheimer’s disease? J Alzheimers Dis. 2007 May;11(2):229-40.

25. Gulyaeva NV, Dupin AM, Levshina IP. Carnosine prevents activation of free-radical lipid oxidation during stress. Bull Exp Biol Med. 1989;107(2):148-152.

26. Stirban A, Negrean M, Stratmann B, et al. Benfotiamine prevents macro- and microvascular endothelial dysfunction and oxidative stress following a meal rich in advanced glycation end products in individuals with type 2 diabetes. Diabetes Care. 2006 Sep;29(9):2064-71.

27. Stracke H. A benfotiamine-vitamin B combination in treatment of diabetic polyneuropathy. Exp Clin Endocrinol Diabetes. 1996;104:311-16.

28. Williams ME, Bolton WK, Khalifah RG, et al. Effects of pyridoxamine in combined phase 2 studies of patients with type 1 and type 2 diabetes and overt nephropathy. Am J Nephrol. 2007;27(6):605-14.

29. Gasic-Milenkovic J, Loske C, Münch G. Advanced glycation endproducts cause lipid peroxidation in the human neuronal cell line SH-SY5Y. J Alzheimers Dis. 2003 Feb;5(1):25-30.

30. Hsieh CL, Yang MH, Chyau CC, et al. Kinetic analysis on the sensitivity of glucose- or glyoxal-induced LDL glycation to the inhibitory effect of Psidium guajava extract in a physiomimic system. Biosystems. 2007 Mar;88(1-2):92-100.

31. Lunceford N, Gugliucci A. Ilex paraguariensis extracts inhibit AGE formation more efficiently than green tea. Fitoterapia. 2005 Jul;76(5):419-27.

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HA Lip Balm

Restoration Therapy™ Pure HA Lip Balm is a premium lip balm that helps lips feel and look smoother and softer, and that helps reduce the appearance of fine lip lines. Smooth and silky, HA Lip Balm is naturally preserved and enriched with pure hyaluronic acid to moisturize, plump and protect lips. Gently massage onto the lips daily or as needed.

Liquid Glucosamine Plus

Liquid Glucosamine – Now New and Improved! Our Liquid Glucosamine is better than ever, with the addition of pure hyaluronic acid, MSM and collagen. Liquid Glucosamine Plus also provides increased levels of chondroitin sulfate for enhanced joint lubrication. This great tasting blend is naturally sweetened and low in simple sugars, and is a convenient and delicious way to supply your body with key nutrients that help build and maintain healthy joints. Used regularly, Liquid Glucosamine Plus can help restore joint mobility and flexibility, reduce inflammation and accelerate regeneration of cartilage. The perfect alternative to encapsulated formulas.

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Energy and memory power in a convenient packet. This great tasting, fast acting powder is a convenient way to enhance energy production while providing an immediate, noticeable improvement in mental clarity and focus. Mixed with water or other beverage, Dynamic Duo® delivers a fog-clearing dose of caffeine, complemented with substantial levels of neurotransmitter precursors and key vitamins and minerals, so you get a physical and mental boost without jitters or crash. Dynamic Duo is perfect for physical activities, and a great way to boost brain power for tasks requiring prolonged mental concentration and focus. With only 2 grams of fructose per serving, Dynamic Duo is a nutritious alternative to sugar-laden energy drinks. Convenient, take-anywhere single serve packets (30 per package). Also contains acesulfame-K and sucralose.

HerBalance™ Cream (#2101) is Now Gentle Changes®

Our best-selling progesterone cream now has a new name. The formula is unchanged and still comes in a convenient 2oz dispenser pump. HerBalance™ Cream with pregnenolone (#2104 formerly #1101) features the same great formula with the addition of pregnenolone, the “mother of all hormones.” Now also packaged in a 2 oz pump.

If you are experiencing unexplained weight gain, depression, fatigue, mood swings, loss of libido, PMS, memory loss, hair loss or a combination of these symptoms, it may simply be an imbalance between your estrogen and progesterone levels. HerBalance and Gentle Changes provide USP progesterone in a moisturizing cream enhanced with natural oils from lemon grass, aloe vera, carrot, and avocado. Select antioxidants like extracts of grape seed and rosemary along with vitamins E and A make this formula a woman’s best friend. Apply to soft skin areas and massage well into skin. Use in the morning and evening.

Surveys have shown that almost one-third of adults report having fatigue,¹ and 24 percent of patients report that their fatigue is a major health problem.² Many scientists believe that one cause of fatigue is mitochondrial dysfunction.³ Mitochondria are structures within cells primarily responsible for energy production. The mitochondria are often referred to as the powerhouse of the cell, and are responsible for cellular respiration and the resulting generation of adenosine tri-phosphate (ATP). ATP is the chemical energy currency in the cell. The body produces an amazing 50 to 75 kg of ATP per day.⁴ There are three main pathways used to generate energy: cellular respiration including glycolysis and the citric acid cycle, oxidative phosphorylation, and beta-oxidation. Mitochondrial dysfunction results in decreased ATP production and thus, may lead to fatigue.

Aging, Fatigue, and Mitochondrial Function

Normal mitochondrial function is imperative for optimal energy production. Aging cells have a diminished ability to produce ATP due to changes in mitochondrial structure and function. Aging has been shown to decrease the efficiency of mitochondrial oxidative phosphorylation, which provides the majority of ATP production. Aging also increases the production of damaging free radicals such as reactive oxygen species (ROS) in the mitochondria.⁵ Cells have several antioxidant enzymes to remove excess ROS from causing damage; however, these enzymes, as well as the enzymes required for oxidative phosphorylation, decrease with age.⁶ Mitochondria have their own DNA, and research indicates that mitochondrial DNA mutations begin accumulating in cells in individuals after the mid-thirties,⁷ which contributes to the decreased ATP production and increased levels of ROS seen with increasing age.⁸ Also, researchers have shown that the loss of muscle mass and function seen with aging is associated with mitochondrial damage in muscle cells.⁹

Numerous diseases are associated with mitochondrial dysfunction such as Parkinson’s disease, Alzheimer’s disease, coronary artery disease, chronic fatigue syndrome (CFS), fibromyalgia, and diabetes, among others.¹⁰ Fatigue, in particular, is associated with mitochondrial dysfunction. One study found that muscle biopsies indicate that post-viral fatigue syndrome may be due to mitochondrial dysfunction precipitated by a virus infection.¹¹ Evidence also indicates that fatigue seen in other conditions such as metabolic syndrome is due to excess cellular oxidative stress caused by free radicals leading to oxidative damage to mitochondria, and resulting in reduced efficiency of mitochondrial energy production.¹² Studies have also shown that patients suffering with chronic fatigue have improved with supplementation of mitochondrial nutrients and antioxidants, showing a reduction in damage to mitochondrial membranes, restoring mitochondrial energy production, protecting cellular structures and enzymes from oxidative damage, and decreasing fatigue.¹³

Nutrients to Support Mitochondrial Function

While there are a number of nutrients shown to improve various aspects of mitochondrial function, there are seven nutrients that can be especially effective and act synergistically to improve mitochondrial function. These seven nutrients are L-carnitine, lipoic acid, N-acetyl-cysteine, succinic acid, EDTA (all found in Mito-Boost® Caps), plus D-ribose, and Coenzyme Q10.

Carnitine plays an important role in fatty acid metabolism and is essential for mitochondrial energy production. Acetyl-L-carnitine is a derivative of carnitine and is a precursor to the molecule acetyl coenzyme A, important in the citric acid cycle. N-acetyl-carnitine also assists in the transportation of long-chain fatty acids into the mitochondria for beta-oxidation. Beta-oxidation is the process in which fatty acids are broken down in mitochondria to generate Acetyl-CoA, the entry molecule for the citric acid cycle. The carnitines also have significant antioxidant activity, providing a protective effect against lipid peroxidation and oxidative stress.

Researchers have shown that patients with chronic fatigue syndrome have significantly lower levels of serum acylcarnitine, total carnitine, and free carnitine. Additionally, the study showed that serum levels of total and free carnitine correlated with the clinical presentation, as higher carnitine levels correlated with better functional capacity.¹⁴ Similar studies also showed that the concentration of serum acylcarnitine in patients with chronic fatigue syndrome (CFS) tended to increase to normal levels with the recovery of general fatigue.¹⁵ These studies suggest that mitochondrial dysfunction may contribute to or cause the symptoms of general fatigue, myalgia, muscle weakness, and post-exertional malaise in patients with CFS. In addition, numerous cardiovascular diseases exhibit similar energy metabolism dysfunction in that ATP synthesis is decreased due to inadequate fatty-acid fuels delivery to the mitochondria, and L-carnitine levels are decreased in these diseases.¹⁶

Lipoic acid is a potent antioxidant and has the ability to protect and repair age-induced mitochondrial DNA damage, thereby up-regulating mitochondrial function and improving energy production.¹⁷ Animal studies have shown that supplementation with lipoic acid has dramatic effects on improving age-related declines in mitochondrial function. Lipoic acid reverses the decline in oxygen consumption, increases mitochondrial membrane potential, decreases levels of ROS and markers of lipid peroxidation, increases ambulatory activity and improves the age-associated decline of memory, increases the levels of antioxidants, and restores the activity of key enzymes.¹⁸ Interestingly, numerous studies have shown that acetyl-L-carnitine in combination with lipoic acid increases cellular metabolism and lowers oxidative stress better than either compound alone.¹⁹

N-acetyl cysteine (NAC) is a precursor for glutathione, a potent antioxidant, and stimulates the enzymes involved in glutathione regeneration. NAC also exhibits antioxidant properties of its own, counteracting the effects of reactive ROS and protecting mitochondrial proteins from damage. NAC has been shown to prevent programmed cell death (apoptosis) in cultured nerve cells and increases activity of mitochondrial complex proteins.^20-21 Additional studies have demonstrated that NAC supplementation decreased age-related memory loss, with decreased levels of oxidants in mice.²² Research also indicates that NAC supplementation directly improves mitochondrial energy production efficiency.²³

Ribose is a five-carbon sugar used by all living cells and is an essential component for energy production. Ribose provides the necessary substrate for synthesis of nucleotides, which form major cellular components such as ATP. The availability of ribose determines the rate at which these nucleotides can be made by the cells. In one study, D-ribose was supplemented to patients with fibromyalgia and/or chronic fatigue syndrome at a dose of 5 grams three times daily. Compared to baseline, patients reported significant improvement in all five categories measured including energy, pain intensity, sleep, mental clarity, and well-being with D-ribose supplementation. In fact, 66 percent of patients reported significant improvement, with an average increase in energy of 45 percent, and an average improvement in overall well-being of 30 percent.²⁴ Research also indicates that in muscle, ribose can accelerate ATP synthesis by up to 4.3-fold and increase energy salvage by up to 8-fold, which is important for muscle function and athletic performance.²⁵ In addition, pre- and post-exercise supplementation with D-ribose decreases free radical formation.²⁶

Coenzyme Q10 (CoQ10) is a compound made by the body and primarily functions as an antioxidant, membrane stabilizer, and a cofactor in cellular respiration. CoQ10 is important in oxidative phosphorylation, and found in highest levels in the cells with the greatest energy demand, the heart and liver. CoQ10 decreases with age, which may contribute to age-related mitochondrial dysfunctions. In one study, researchers showed that in patients with chronic fatigue of unknown etiology for at least 6 months, 69 percent reported improvement with CoQ10 supplementation.²⁷ CoQ10 has also been shown to alleviate fatigue, improve physical performance, and decrease the recovery period with fatigue-inducing physical activity.²⁸

Another substance important for mitochondrial health is succinate (succinic acid), a citric acid cycle intermediate, in which succinate is converted to fumarate. Supplementation with succinate has shown benefit in patients with mitochondrial defects.²⁹ Finally, EDTA can be used with all of the nutrients mentioned above to stabilize mitochondrial membranes.

Conclusion

Fatigue is a common complaint and presents with numerous medical conditions. However, optimizing mitochondrial function improves energy production, and may help alleviate fatigue. Nutrients such as L-carnitine, lipoic acid, N-acetyl-cysteine, succinate, and EDTA (all found in Mito-Boost® Caps), combined with D-ribose and CoQ10 have all been shown to improve mitochondrial energy production.

References

1. Bates DW, Schmitt W, Buchwald D, et al. Prevalence of fatigue and chronic fatigue syndrome in a primary care practice. Arch Intern Med. 1993 Dec 27;153(24):2759-65.

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

3. Bains W. Treating Chronic Fatigue states as a disease of the regulation of energy metabolism. Med Hypotheses. 2008 Oct;71(4):481-8.

4. Di Carlo SE, Coliins HL. Submitting illuminations for review. Advan Physiol Edu. 2001;25:70–71.

5. Lesnefsky EJ, Hoppel CL. Oxidative phosphorylation and aging. Ageing Res Rev. 2006 Nov;5(4):402-33.

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

7. Fahn HJ, Wang LS, Hsieh RH, et al. Age-related 4,977 bp deletion in human lung mitochondrial DNA. Am J Respir Crit Care Med. 1996 Oct;154(4 Pt 1):1141-5.

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

9. Dirks AJ, Hofer T, Marzetti E, et al. Mitochondrial DNA mutations, energy metabolism and apoptosis in aging muscle. Ageing Res Rev. 2006 May;5(2):179-95.

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

11. Behan WM, More IA, Behan PO. Mitochondrial abnormalities in the postviral fatigue syndrome. Acta Neuropathol. 1991;83(1):61-5.

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

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

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

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

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

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

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

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

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

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

22. Martínez M, Hernández AI, Martínez N. N-Acetylcysteine delays age-associated memory impairment in mice: role in synaptic mitochondria. Brain Res. 2000 Feb 7;855(1):100-6.

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

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

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

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

27. Bentler SE, Hartz AJ, Kuhn EM. Prospective observational study of treatments for unexplained chronic fatigue. J Clin Psychiatry. 2005 May;66(5):625-32.

28. Mizuno K, Tanaka M, Nozaki S, et al. Antifatigue effects of coenzyme Q10 during physical fatigue. Nutrition. 2008 Apr;24(4):293-9.

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

There is an enormous amount of medical literature on the deleterious effects of negative emotions (distress, depression, fear, anxiety, anger, hostility, etc.) on cardiovascular disease. Stressors can be acute (such 9/11 or Hurricane Katrina) or chronic (job stress, marital or relationship tensions, or the burden of care giving). Adverse cardiovascular effects in response to stressful situations can be severe, even fatal, and include the following:^1-5

• Increased heart rate
• Elevated blood pressure
• Increased oxygen demand on the body
• Electrical instability in the heart, which leads to disturbances of cardiac rhythm (ventricular tachycardia, ventricular fibrillation, atrial fibrillation).
• Spasms of coronary blood vessels, leading to myocardial ischemia (inadequate blood flow to the heart)
• Myocardial infarction (heart attack)
• Development of coronary atherosclerosis
• Decreased heart rate variability (a measure of the beat-to-beat variations in heart rate).

In this article, we will focus on the way in which stress affects the heart and the neuroendocrine response to stress.

Stress and Cortisol—a Dangerous Combination

Psychological stress produces changes in the sympathetic-parasympathetic balance of the nervous system and alterations of the hypothalamic-pituitary-adrenal (HPA) axis, which negatively affects the cardiovascular system.^{3, 5-7}

The HPA axis is a network of glands linking the brain and endocrine system that mediate stress and avert danger (producing the so-called “fight-or-flight” response). When a stressor is perceived, the hypothalamus, deep within the brain, secretes CRH (corticotropin-releasing hormone), which in turn acts on the pituitary gland to secrete ACTH (adrenocorticotropic hormone), triggering the release of cortisol from the adrenal glands. Under normal conditions, cortisol is involved in blood pressure regulation and cardiovascular and immunologic function; in response to stress, higher levels are secreted in order to facilitate energy production for optimal brain function. Increased cortisol production has been documented in several experiments measuring physiological responses to various stressors such as public speaking and mental arithmetic,⁸ noise and shock,⁹ and stressful events.⁷

The HPA axis is designed with a feedback control feature, so that when the danger or stressor has been averted, the hypothalamus halts the secretion of CRH, which ultimately restores cortisol levels to normal. However, during periods of prolonged stress, the “fight-or-flight” response of the sympathetic nervous system can go awry and remain constantly activated, resulting in chronic cortisol over-secretion and suppression of the calming parasympathetic nervous system.

It has been demonstrated that situations involving negative emotions result in impairment in feedback control of the HPA axis, leading to the release of chronically high levels of cortisol.^{7, 10} Elevated cortisol is a mediating factor in the development of heart disease and other medical disorders.^{2-5, 7, 10}

Research over the past 50 years has shown that certain personality types such as 1) “Type A” (a combination of aggression, competitiveness, impatience, hostility, and anger);⁷ 2) the recently proposed “Type D” or “distressed” personality (characterized by depressed mood, anxiety, anger, hostility coupled with social inhibition);^{7, 11-13} and 3) major depressives^{6-7, 11} are associated with a greater cortisol reactivity to stress, and therefore, higher rates of heart disease.

Emotions are so strongly linked to heart health that scientists estimate between 20 and 40 percent of sudden cardiac deaths are precipitated by acute emotional stressors.³

The Heart Disease Link

Cortisol is involved in many pathways that promote heart disease. For one, it inhibits growth hormone production, which is associated with a higher risk for premature cardiovascular disease.⁷ Second, by inhibiting the growth hormone and gonadal axes, it stimulates visceral fat accumulation,⁷ a precursor to metabolic syndrome, a potentially deadly combination of abdominal obesity, hypertension, low high-density lipoprotein, high blood sugar and insulin resistance. Metabolic syndrome is a potent risk factor for heart disease.¹⁴

In addition, the behavioral aspect of negative emotional states should not be underestimated. Unhealthy, stress-induced habits such as smoking, physical inactivity, poor diet and overeating can lead to overweight and metabolic syndrome, and ultimately, heart disease.

The Whitehall II Study

There are thousands of studies linking stress and heart disease, but one that stands out is the Whitehall II study, a large-scale prospective cohort study of over 10,000 English civil servants, aged 35 to 55, conducted between 1985 and 1988 in order to investigate the relationships between work, stress, and health. Dozens of investigators have examined the data, and multiple follow-ups have been performed, some still ongoing.

In this study published in the European Heart Journal, researchers reported a definite association between chronic work-related stress and coronary heart disease in the Whitehall cohort. They also reported that stressed workers were prone to physical inactivity, poor diet, the metabolic syndrome and its components, lower heart rate variability, and higher cortisol levels.

The study concludes, “Work stress may be an important determinant of coronary heart disease (CHD) among working-age populations, which is mediated through indirect effects on health behaviors and direct effects on neuroendocrine stress pathways.”¹⁵

This conclusion underscores the fact that stress affects the heart both directly, through HPA axis activation, as well as indirectly, through the development of unhealthy behaviors that precipitate dangerous conditions (overweight and metabolic syndrome), which in turn are risk factors for CHD.

In a related report of the Whitehall II study data, other researchers established an association between psychological distress, depression and an increased incidence of CHD.⁶

Preventing and Managing Stress

Negative emotions, as the above research shows, can set the stage for heart disease. There are a number of ways to take action to counter stress and lower cortisol by making some important behavioral and lifestyle changes:

• Get regular exercise.
• Eat a healthy diet rich in fruit, vegetables and whole grains
• Don’t smoke
• Drink alcohol in moderation
• Practice stress management techniques such as meditation, yoga, biofeedback, progressive muscle relaxation, guided imagery
• Seek social or professional support

In addition, targeted nutritional supplements have been shown to alleviate stress and anxiety. These include:

Withania somnifera, also known as Ashwaganda, is an adaptogen reported to have mood stabilizing,¹⁶ anxiolytic (anxiety-reducing) and antidepressant actions.^16-17 It also has been shown to attenuate physiological stress responses¹⁸ and positively influence the endocrine and central nervous systems.¹⁹ Most recently, Withania was found to directly provide cardioprotective effects.²⁰

Gamma-Aminobutyric Acid (GABA) is the major inhibitory neurotransmitter in the brain (i.e., it regulates brain excitability and nerve transmission). Either low GABA levels or decreased GABA function is associated with anxiety, depression, insomnia, and epilepsy.²¹ In human studies, GABA supplementation has been shown to induce relaxation and reduce anxiety.^21-22

L-Theanine is an amino acid found in green tea that has long been used as a relaxant. In addition to reducing stress-induced physiological responses (changes in heart rate, sympathetic nervous system activation),²³ this calming agent also decreases the brain’s production of excitatory neurotransmitters while increasing inhibitory neurotransmitters such as GABA.²⁴

Valeriana officinalis, one of 250 species of valerian, has been used as a sleep aid and anti-anxiety agent since antiquity. Its antidepressant properties have also been described.25 It exerts a regulatory effect on the autonomic nervous system.²⁶ and has been demonstrated to bind to benzodiazepine²⁶ and GABA receptors,^26-27 providing a tranquilizing effect, improving sleep quality and decreasing the time it takes to fall asleep.

Relora® is a proprietary blend of extracts of Magnolia officinalis and Phellodendron amurense. The active constituent of Magnolia officinalis, honokiol, exerts an anti-anxiety effect similar to that of the benzodiazepine, diazepam, without side effects.²⁸ Recently, A U.S. Patent was granted for use of an extract of Magnolia officinalis for stress-related conditions involving elevated cortisol levels.

Berberine, the active component of Phellodendron amurense, demonstrates anxiolytic and antidepressant qualities.²⁸ In a recently published study, Relora® was effective in reducing temporary, transitory anxiety.²⁸ An earlier pilot study reported a reduction in cortisol levels and perceived stress.²⁹

Using combinations of these stress-relievers, found in Allay™ (containing Withania somnifera, GABA, L-theanine, and valerian extract) and Cortisol Control (a synergistic blend of Relora® and Sensoril®, a patented extract of Withania somnifera), can help stabilize cortisol levels and increase relaxation. These effects can provide a strong foundation for a healthy heart.

Conclusion

The connection between negative emotional states and heart disease has been clearly established. Psychological stress, through activation of the neuroendocrine system, can have severe, even devastating effects. The good news is stress-related symptoms can be ameliorated and our health positively influenced through life-style changes, behavioral techniques, and the use of clinically proven natural supplements.

References

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

2. Dimsdale JE. Psychological stress and cardiovascular disease. J Am Coll Cardiol. 2008 Apr 1;51(13):1237-46.

3. Vlastelica M. Emotional stress as a trigger in sudden cardiac death. Psychiatr Danub. 2008 Sep;20(3):411-4.

4. Steptoe A, Brydon L. Emotional triggering of cardiac events. Neurosci Biobehav Rev. 2008 May 3.

5. Brotman DJ, Golden SH, Wittstein IS. The cardiovascular toll of stress. Lancet. 2007 Sep 22;370(9592):1089-100.

6. Stansfeld SA, Fuhrer R, Shipley MJ, Marmot MG. Psychological distress as a risk factor for coronary heart disease in the Whitehall II Study. Int J Epidemiol. 2002 Feb;31(1):248-55.

7. Sher L. Type D personality: the heart, stress, and cortisol. Q J Med. 2005 May;98(5):323-9.

8. Al’Absi M, Bongard S, Buchanan T, Pincomb GA, Licinio J, Lovallo WR. Cardiovascular and neuroendocrine adjustment to public speaking and mental arithmetic stressors. Psychophysiology. 1997 May;34(3):266-75.

9. Lovallo WR, Pincomb GA, Brackett DJ, Wilson MF. Heart rate reactivity as a predictor of neuroendocrine responses to aversive and appetitive challenges. Psychosom Med. 1990 Jan-Feb;52(1):17-26.

10. Todaro JF, Shen BJ, Niaura R, Spiro A 3rd, Ward KD. Effect of negative emotions on frequency of coronary heart disease (The Normative Aging Study). Am J Cardiol. 2003 Oct 15;92(8):901-6.

11. Steptoe, A, Molloy, GJ. Personality and Heart Disease. Heart. 2007; 93:783-784.

12. Denollet J, Pedersen SS, Vrints CJ, Conraads VM. Usefulness of type D personality in predicting five-year cardiac events above and beyond concurrent symptoms of stress in patients with coronary heart disease. Am J Cardiol. 2006 Apr 1;97(7):970-3.

13. Molloy GJ, Perkins-Porras L, Strike PC, Steptoe A. Type-D personality and cortisol in survivors of acute coronary syndrome. Psychosom Med. 2008 Oct;70(8):863-8.

14. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002 Jan 16;287(3):356-9.

15. Chandola T, Britton A, Brunner E, et al. Work stress and coronary heart disease: what are the mechanisms? Eur Heart J. 2008 Mar;29(5):640-8.

16. Bhattacharya SK, Bhattacharya A, Sairam K, Ghosal S. Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: an experimental study. Phytomedicine. 2000 Dec;7(6):463-9.

17. Gupta GL, Rana AC. Protective effect of Withania somnifera dunal root extract against protracted social isolation induced behavior in rats. Indian J Physiol Pharmacol. 2007 Oct-Dec;51(4):345-53.

18. Bhattacharya SK, Muruganandam AV.Adaptogenic activity of Withania somnifera: an experimental study using a rat model of chronic stress. Pharmacol Biochem Behav. 2003 Jun;75(3):547-55.

19. Mishra LC, Singh BB, Dagenais S. Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review. Altern Med Rev. 2000 Aug;5(4):334-46.

20. Mohanty IR, Arya DS, Gupta SK. Withania somnifera provides cardioprotection and attenuates ischemia-reperfusion induced apoptosis. Clin Nutr. 2008 Aug;27(4):635-42.

21. No authors listed. Gamma-aminobutyric acid (GABA), Monograph. Altern Med Rev. 2007 Sep;12(3):274-9.

22. Abdou AM, Higashiguchi S, Horie K, Kim M, Hatta H, Yokogoshi H. Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans. Biofactors. 2006;26(3):201-8.

23. Kimura K, Ozeki M, Juneja LR, Ohira H. L-Theanine reduces psychological and physiological stress responses. Biol Psychol. 2007 Jan;74(1):39-45.

24. Yamada T, Terashima T, Okubo T, Juneja LR, Yokogoshi H. Effects of theanine, r-glutamylethylamide, on neurotransmitter release and its relationship with glutamic acid neurotransmission. Nutr Neurosci. 2005 Aug;8(4):219-26.

25. Hattesohl M, Feistel B, Sievers H, Lehnfeld R, Hegger M, Winterhoff. Extracts of Valeriana officinalis L. s.l. show anxiolytic and antidepressant effects but neither sedative nor myorelaxant properties. Phytomedicine. 2008 Jan;15(1-2):2-15.

26. No authors listed. Valeriana officinalis, Monograph. Altern Med Rev. 2004 Dec;9(4):438-41.

27. Benke D, Barberis A, Kopp S, et al. GABA(A) receptors as in vivo substrate for the anxiolytic action of valerenic acid, a major constituent of valerian root extracts. Neuropharmacology. 2008 Jun 17. Published Online Ahead of Print.

28. Kalman DS, Feldman S, Feldman R, Schwartz HI, Krieger DR, Garrison R. Effect of a proprietary Magnolia and Phellodendron extract on stress levels in healthy women: a pilot, double-blind, placebo-controlled clinical trial. Nutr J. 2008 Apr 21;7:11.

29. Garrison R, Chambliss WG. Effect of a proprietary Magnolia and Phellodendron extract on weight management: a pilot, double-blind, placebo-controlled clinical trial. Altern Ther Health Med. 2006 Jan-Feb;12(1):50-4.

Often, we don’t pay attention to our intestinal health unless we develop an obvious gastrointestinal disease. Yet, the GI tract is the absolute barrier between the burdensome outside world that enters our bodies in the form of foods and contaminates (herbicides, pesticides, heavy metals and an array of other health saboteurs) and our well ordered 75 trillion cells that work in harmony to sustain our existence. Therefore, regardless of whether an individual has any overt signs of gastrointestinal dysfunction, fortifying the GI tract enhances the ability for nutrients from food and supplements to be most optimally absorbed.

Some 60 to 70 million people are affected by overt diagnosable digestive diseases,1 yet tens of millions of others suffer from subclinical GI health issues that alter their ability to absorb nutrients from their diet and supplements, ultimately undermining even the most proactive individual’s attempt to truly take care of his or her health. Annually, an astounding 234,000 people die from GI diseases including cancer.2 Yet, far more people (14 million per year) end up in the hospital from nonfatal GI conditions.3

Diagnosed GI health conditions are just that, confirmation of disease being present. This amounts to finally there is officially enough symptoms and a confirmatory diagnostic test to document either anatomical or functional dysfunction. However, it can take tens of thousands if not millions of cells to be sufficiently damaged prior to having the ability to perceive there is a problem. Proactive GI health care is of paramount importance in the endeavor to minimize the risk of becoming one of the 6 million diagnostic and therapeutic in-patient hospitalization procedures conducted annually4 or one of the approximately 45 million outpatient visits.5 This has a dramatic impact on quality of life with 1.9 million people disabled due to GI disease.6

Proactive Approach to GI Health

Without optimal health in the alimentary tract there cannot be true wellness elsewhere. For the body to heal and wellness to prevail, toxic waste absorption must be minimized.

Though the entire GI tract works in symphonic harmony, we must limit ourselves in this article to the large intestine’s anatomy and physiology. The large intestine is approximately 60 inches in length (about 5 feet) and is comprised of four segments: the ascending colon (8 inches); transverse colon (18 inches); descending colon (approximately 12 inches); and sigmoid colon (18 inches). (Fig. 1).

The large intestine absorbs about 90 percent of the water content it receives from the small intestine. If this slurry of food material and moisture remains in the colon too long, excess moisture is absorbed and toxins and waste burden are reabsorbed disproportionately, irritating the colonic lining. This is why, when individuals fail to have 2 to 3 bowel movements per day, they feel ill and tired. Furthermore, their stools are harder and drier, for the body has reabsorbed the toxic wastewater. This process of absorption and reabsorption serves as the mandate to nourish the GI tract daily—even when not experiencing GI distress.

A Life-Sustaining Function

The healthy intestinal lining is a selective barrier that normally only allows properly digested fats, proteins, and starches to enter the bloodstream. The colonic lining that comes in contact with food, bacteria, toxins and other pathogens is called the mucosa and is an epithelial (single layer of cells) lining that regenerates every 3-8 days. For proper maintenance of this nutrient-dependent barrier, sufficient substrates for healing, repair and regeneration must be present.

Nutrient absorption across this GI interface that also protects against harmful agents occurs via a few mechanisms:

Diffusion is the process by which nutrients such as potassium, magnesium, sodium, chloride and free fatty acids diffuse through intestinal cells.

Active transport allows for amino acids, fatty acids, glucose, minerals, and vitamins to cross through cells.

Tight Junction (Desmosomes) is a third way substances can pass into the circulatory system from the intestines. The tight junction spaces between cells that line the intestines are normally sealed. However, when the intestinal lining becomes irritated, the junctions loosen and allow unwanted larger molecules in the intestines to pass through into the blood. This can trigger immediate damage and immune system reactions since these large molecules are perceived as foreign. Much like the initial crack in a large dam, without immediate repair, progressive damage occurs to the intestinal lining, eventually allowing disease-causing bacteria, undigested food particles, and toxins to pass directly into the body. A cascade of events ensues as  the immune system becomes involved in generating antibodies and cytokines that produce oxidative damage, localized irritation and inflammation throughout the body. This process increases inflammatory markers such as C-reactive protein (CRP), a known risk factor for cardiac damage and in this case serving as the proverbial coal miners’ canary alert that preemptive action is required.

This inflammation can result in IBS (irritable bowel syndrome), which affects 20 percent of Americans.7 Additionally, in 2004, there were 73,997 men and 71,086 women diagnosed with colorectal cancer.8

Leaky Gut Syndrome

Disturbance of the tight junctions contribute to leaky gut syndrome (LGS). The symptoms that can arise range from subtle to severe depending on breach of the integrity of the intestinal natural defenses. Individuals with LGS can experience one or more of these symptoms: abdominal pain, anxiousness, asthma, chronic joint pain, chronic muscle pain, confusion, fuzzy or foggy thinking, gas, indigestion, mood swings, poor immunity, recurrent infections, skin rashes, diarrhea, poor memory, constipation, bloating, fatigue and feeling toxic or hung-over. Leaky gut syndrome is associated with many conditions (See Table 1).

Nutritional Support for the Colon

Specific supplements, such as those mentioned below (all found in GI Cell Support),  can deliver critical building blocks for daily repair of the GI tract and also help soothe irritation that arises from innate colonic function.

Glutamine

Glutamine is the most abundant free amino acid in the body.9 Though it is classified as a non-essential amino acid, glutamine is absolutely essential for maintaining intestinal structure.10 Glutamine serves as metabolic fuel for enterocytes that line the colon and affect cell proliferation. The GI tract has the largest demand for glutamine in the body.11 Insufficient glutamine can present with atrophy, ulceration, and necrosis of the colon lining.

DGL

Most of the research on deglycyrrhizinated licorice (DGL) has been focused on upper GI health, including ulcer healing. Colon health is directly dependent upon the proper functioning of the entire GI tract. DGL seems to be similar to carbenoxolone, a semisynthetic derivative of glycyrrhetic acid used outside the US for treating gastric and duodenal ulcer disease.12-13 DGL utility is not limited to upper GI health, in the clinical setting it has demonstrated great utility in lessening intestinal irritation and related symptoms.

N-Acetyl-Glucosamine

N-acetyl glucosamine is the acetylated derivative of the amino sugar glucosamine. In inflammatory bowel disease (IBD), N-acetylation of glucosamine is relatively deficient, possibly reducing the synthesis of the gastric and intestinal mucosa’s protective glycoprotein cover.14

Marshmallow

Marshmallow leaf and root contain mucilage polysaccharides that soothe and protect mucous membranes from local irritation by creating a protective layer.15-16 The mucilage properties can also have antimicrobial, spasmolytic, and wound-healing effects.17-18

Berberine

Maintaining healthy GI flora is essential. Berberine possesses antimicrobial effects including antibacterial, antifungal, antimycobacterial and antiprotozoal activity.19-20 Berberine has demonstrated activity against Staphylococcus aureus, Streptococcus pyogenes, Eschericha coli, Shigella boydii, Vibrio cholerae, Mycobacterium tuberculosis, Candida albicans, Candida tropicalis, Trichophyton mentagrophytes, Microsporum gypseum, Cryptococcus neoformans, Sporotrichum schenkii, Entamoeba histolytica, and Giardia lamblia.21-24

Berberine also helps control inflammation in the GI tract by selectively inhibiting cyclooxygenase (COX)-2 expression and blocking the proinflammatory cytokines interleukin-1 (IL1)-beta and tumor necrosis factor (TNF)-alpha as well as nuclear factor-kappaB, the transcription factor responsible for regulation of cytokine production.25

Cabbage

Historically called vitamin U, cabbage does not meet the official criteria to achieve vitamin status. However, cabbage constituents offer significant protection to the GI tract and thus the body in general. Individuals who consume large amounts of cabbage and other Brassica vegetables have a lower risk of developing stomach and colorectal cancer.26 In 1952, 100 peptic ulcer patients drank 4 glasses of fresh, raw cabbage juice daily. Patients indicated dramatically reduced pain, while x-rays demonstrated significantly reduced healing time. Eighty-one percent of the patients were symptom-free within one week, and over two thirds were better within four days.27 Cabbage also possesses antioxidant effects.28

Slippery Elm

The inner bark of slippery elm contains mucilage constituents that are demulcent and emollient. When used internally, slippery elm preparations trigger gentle stimulation of nerve endings in the GI tract, leading to mucous secretion that coats and protects the delicate lining of the intestines from ulcers, excess acidity, ingested irritants and toxins.15, 17-18

Phosphatidylcholine

The clinical importance of phosphatidylcholine (PC) is illustrated by a 2007, randomized, double-blind, placebo-controlled study showing that patients with ulcerative colitis can benefit from PC supplementation. It was shown that low levels of PC in colonic mucus are a likely contributory factor involved in the development of ulcerative colitis.

The study authors concluded, “Phosphatidylcholine reduced corticosteroid dependence more than placebo in patients with chronic steroid-refractory ulcerative colitis….”29 This research correlates with the findings in clinical practice that when PC is supplemented it supports the GI function and cellular synthesis.

Gamma Oryzanol

Gamma oryzanol contributes ferulic esters extracted from rice bran oil that possess antioxidant properties. It is highly regarded in Japan to promote a healthy gastrointestinal environment. There appears in animal models to be a modulation of pituitary secretion, inhibition of excess gastric acid secretion, and inhibition of platelet aggregation.30 There is also evidence of cholesterol-lowering properties by decreasing cholesterol absorption from the gut.31

Summary

Maintaining healthy GI function is foundational to all other health pursuits. Even those fortunate enough not to suffer from GI dysfunction should take steps to protect healthy GI function, which is critical for sustained healthy aging. Clinical practice and testing clearly demonstrate it is the rare individual who has a totally pristine GI tract. Optimal absorption of nutrients from foods and supplements consumed depend upon optimal GI health. Use of specific nutrients to protect, soothe and support the colon is the first step toward health optimization for the entire body.

References

1. Adams PF, Hendershot GE, Marano MA. Current estimates from the National Health Interview Survey, 1996. National Center for Health Statistics. Vital Health Stat. 1999;10(200).

2. National Center for Health Statistics. (Technical Appendix from Vital Statistics of the United States: Mortality). 2002. Hyattsville, Maryland: 2004.

3. Kozak LJ, Owings MF, Hall MJ. National Hospital Discharge Survey: 2002 annual summary with detailed diagnosis and procedure data. National Center for Health Statistics. Vital Health Stat. 2005;13(158).

4. Burt CW, Schappert SM. Ambulatory care visits to physician offices, hospital outpatient departments, and emergency departments: United States, 1999–2000. National Center for Health Statistics. Vital Health Stat. 2004;13(157).

5. Collins, JG. Prevalence of selected chronic conditions: United States, 1990–1992. National Center for Health Statistics. Vital Health Stat. 1997; 10(194).

6. Sandler RS, Everhart JE, Donowitz M, Adams E, Cronin K, Goodman C, Gemmen E, Shah S, Avdic A, Rubin R. The burden of selected digestive diseases in the United States. Gastroenterology. 2002;122:1500–1511.

7. National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/ibs/Accessed January 12, 2008.

8. U.S. Cancer Statistics Working Group. United States Cancer Statistics: 2004 Incidence and Mortality. Atlanta (GA): Department of Health and Human Services, Centers for Disease Control and Prevention, and National Cancer Institute; 2007.

9. Medina MA. Glutamine and cancer. J Nutr. 2001;131:2539S-42S.

10. Sacks GS. Glutamine supplementation in catabolic patients. Ann Pharmacother. 1999;33:348-54.

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

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

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

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

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

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

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

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

19. Amin AH, Subbaiah TV, Abbasi KM. Berberine sulfate: antimicrobial activity, bioassay, and mode of action. Can J Microbiol. 1969;15:1067-76.

20. Sun D, Courtney HS, Beachey EH. Berberine sulfate blocks adherence of Streptococcus pyogenes to epithelial cells, fibronectin, and hexadecane. Antimicrob Agents Chemother. 1988;32:1370-4.

21. Scazzocchio F, Corneta MF, Tomassini L, Palmery M. Antibacterial activity of Hydrastis canadensis extract and its major isolated alkaloids. Planta Med. 2001;67:561-4.

22. Rehman J, Dillow JM, Carter SM, et al. Increased production of antigen-specific immunoglobulins G and M following in vivo treatment with the medicinal plants Echinacea angustifolia and Hydrastis canadensis. Immunol Lett. 1999;68:391-5.

23. Sun D, Courtney HS, Beachey EH. Berberine sulfate blocks adherence of Streptococcus pyogenes to epithelial cells, fibronectin, and hexadecane. Antimicrob Agents Chemother. 1988;32:1370-4.

24. Kaneda Y, Torii M, Tanaka T, Aikawa M. In vitro effects of berberine sulphate on the growth and structure of Entamoeba histolytica, Giardia lamblia and Trichomonas vaginalis. Ann Trop Med Parasitol. 1991;85:417-25.

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

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

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

28. Isbir T, Yaylim I, Aydin M, et al. The effects of Brassica oleraceae var capitata on epidermal glutathione and lipid peroxides in DMBA-initiated-TPA-promoted mice. Anticancer Res. 2000;20:219-24.

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

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

31. Seetharamaiah GS, Chandrasekhara N. Effect of oryzanol on cholesterol absorption and biliary and fecal bile acids in rats. Indian J Med Res. 1990;92:471-5.

Should you give your pets mega doses of supplemental nutrients or is it better to offer them smaller amounts closer to what is seen in nature and which over time will maintain better health? There are advocates on both sides of the question.

I have worked with specialists who use supplements, but don’t start until they can prove there is a deficiency. Following the diagnosis, the doses of supplements are much larger than anything I would normally consider using. At the point of a proven deficiency, I think the mega doses are worthwhile. I just prefer using smaller doses before such a deficiency can develop.

In the apparently healthy animal that just doesn’t seem to have the same hair coat or the same energy that it once had, small doses seem to be a great way to go. This approach can provide necessary nutrients to the cells and the mitochondria that may be missing in some of the dog foods, since not all foods are created equal.

We see more of the problems with the cheap dog foods since the ingredients, while providing the basics, may not have all the antioxidants and other molecules that support real energy and that slow aging.

In the human animal we are now told that we should eat 9 to 13 servings of vegetables and fruits daily. Even with that knowledge, our population is suffering from obesity on a never before seen level. The sad part is I see the same thing in our pet population. If the food is a little low on one essential amino acid, the animal will eat enough to satisfy that need, which means it will get much more than what it needs of the other nutrients. Supplementation can make a real difference in the life of your pet, even when feeding higher quality foods.

With small-dose or large-dose approaches, either can be done by using single source supplements such as acetyl-L-carnitine, Co-Q10 and taurine, or it can be done with formulas that put multiple supplements together in one package such as RejuvaPet. With a product such as RejuvaPet, low-dose therapy is easy and covers a multitude of problems. Consider that this supplement can support increased energy, provide antioxidants, support detoxification and support hormonal metabolism. The first three supplements (acetyl-L-carnitine, Co-Q10 and taurine) support muscle function, cardiac function and cognitive function. Having had very good results in many dogs, I can recommend either of these approaches, the single supplement given separately or the combined supplement formula for ease of administration, depending on what is needed.

Consider the low-dose approach to supplementing for those pets that have some problems showing up on their blood profiles, but nothing specific that can be treated with typical Western medicine. So many problems that age seems to create are helped with low-dose supplementation and may help slow the aging process.

Low Antioxidant Levels Linked to Asymptomatic Coronary Artery Disease

Low plasma concentrations of the antioxidant vitamins A and E and the carotenoids beta carotene and lycopene are significantly associated with atherosclerosis of the carotid arteries, a new study has found.

Atherosclerosis remains clinically mute for a long time and frequently manifests itself with an acute cardiovascular event. The possibility of detecting this disease in a subclinical phase and reducing or reversing its progression is therefore an issue of relevance.

Researchers studied 220 consecutive, asymptomatic participants and examined their carotid arteries by ultrasound to determine the thickness of the arteries and whether the arteries had developed pre-atherosclerotic lesions. A medical history also was taken, a physical examination was performed and blood samples were analyzed for concentrations of antioxidant vitamins and carotenoids.

The scientists found that low concentrations of vitamin A, vitamin E, lycopene and beta carotene were significantly associated with carotid atherosclerosis as measured by increased thickness of the carotid arteries. In addition, marginally higher body mass index and low levels of high-density lipoprotein cholesterol were also associated with carotid atherosclerosis. Other factors considered in the study (total cholesterol, low-density lipoprotein cholesterol, triglycerides and C-reactive protein) were not significantly associated with carotid atherosclerosis.

According to the researchers, “Low plasma concentrations of antioxidant vitamins (vitamins A, E and beta-carotene) and lycopene were associated with early carotid atherosclerotic lesions as measured by carotid intima-media thickness (CIMT). Regular intake of foods rich in lycopene and antioxidant vitamins may slow the progression of atherosclerosis.”

Reference:

Riccioni G, Bucciarelli T, D’Orazio N, Palumbo N, di Ilio E, Corradi F, Pennelli A, Bazzano LA. Plasma Antioxidants and Asymptomatic Carotid Atherosclerotic Disease. Ann Nutr Metab. 2008 Oct 21;53(2):86-90.

Grape Seed Extract May Stop Bacteria Involved in Bad Breath and Gum Disease

A new study suggests that grape seed extract may inhibit the bacteria known to cause bad breath and gum disease.

Periodontitis is a gum disease that destroys the soft tissue and bone supporting the teeth. Thirty to 50 percent of the US population suffers from the condition, which is thought to be the second most common disease worldwide.

In an in vitro study, researchers investigated whether grape seed extract could inhibit Porphyromonas gingivalis and Fusobacterium nucleatum, bacteria responsible for both periodontitis and bad breath. The researchers tested the effects of grape seed extract (97 percent polyphenols) on these two anaerobic bacteria.

The results indicated that grape seed extract exhibited antibacterial activity against the two strains. Moreover, the grape seed extract could penetrate the biofilm that surrounded the bacteria. Biofilms serve to protect bacteria against antimicrobial agents and dental plaque’s biofilm is particularly complex.

Grape seed extract also had an antioxidant activity higher than vitamins C and E, according to measures taken with the Trolox equivalent antioxidant capacity (TEAC) test. This was important to the findings of the study because gum disease originates due to the bacteria’s presence and its biofilm protection, but the disease progresses because of an excess release of reactive oxygen species that trigger the inflammatory process. Grape seed extract’s antioxidant abilities may quench the free radicals implicated in the progression of gum disease.

The researchers concluded, “These findings indicated that GSE could be used in oral hygiene for the prevention of periodontitis.”

Reference:

Furiga A, Lonvaud-Funel A, Badet C. In vitro study of antioxidant capacity and antibacterial activity on oral anaerobes of a grape seed extract. Food Chemistry. 15 April 2009;113( 4);1037-1040. Available online prior to April publication date.

Turmeric Component Protects Against Toxic Compound Consumed in Many Meals

Curcumin, the pigment that gives turmeric its yellow color, may reduce the damaging effects of acrylamide (AA), a potential carcinogen created when starchy foods are baked, roasted, fried or toasted.

Swedish scientists first reported on acrylamide’s widespread presence in the food supply in 2002, when they found unexpectedly high levels of acrylamide in carbohydrate-rich foods. This was of concern since the toxin causes cancer in laboratory rats. Other scientists have found that acrylamide causes DNA to fragment, increases formation of damaging reactive oxygen species (ROS) and triggers the death of liver cells. It is also genotoxic, meaning that it damages a cell’s genetic material affecting the cell’s integrity. Genotoxic substances have the potential to be carcinogens and can cause genetic mutations that lead to the development of tumors.

Due to its antioxidant abilities, researchers studied curcumin’s effects on human liver cells exposed to acrylamide. They found that curcumin significantly reduced the production of reactive oxygen species that occurred in acrylamide-treated cells. Curcumin also inhibited the acrylamide-induced DNA fragments and significantly reduced the acrylamide-triggered cell death, indicating curcumin could ameliorate acrylamide’s known genotoxicity.

The researchers believe that curcumin’s effects are likely due to its antioxidant abilities. They concluded, “Consumption of curcumin may be a plausible way to prevent AA-mediated genotoxicity.”

Reference:

Cao J, Liu Y, Jia L, Jiang LP, Geng CY, Yao XF, Kong Y, Jiang BN, Zhong LF. Curcumin Attenuates Acrylamide-Induced Cytotoxicity and Genotoxicity in HepG2 Cells by ROS Scavenging. J Agric Food Chem. 2008 Nov 14. Published Online Ahead of Print.

Garcinia Cambogia Studied for Possible Effects in IBD and Ulcerative Colitis

A new study suggests that garcinia cambogia extract, known for its weight-loss effects, also can reduce the damage that occurs in ulcerative colitis.

Inflammatory bowel disease (IBD) and ulcerative colitis are thought to result from a disrupted mucosal immune response. These conditions are characterized by oxidative stress and up-regulation of pro-inflammatory substances. In past studies, garcinia cambogia extract has attracted interest due to its ability to protect the gastrointestinal tract.

In the current study, the anti-inflammatory activity of a garcinia cambogia extract was assessed in experimental colitis in rats. The results obtained revealed that garcinia cambogia administration to colitic rats significantly improved the damage in the intestine and substantially reduced inflammatory markers such as the COX-2 enzyme. The researchers believe the anti-inflammatory actions were related to the reduction in DNA damage in colon cells noted during the experiment.

According to the study authors, “The anti-inflammatory effects provided by the garcinia cambogia extract result in an improvement of several parameters analyzed in experimental colitis and could provide a source for the search for new anti-inflammatory compounds useful in IBD treatment.”

Reference:

Dos Reis SB, de Oliveira CC, Acedo SC, da Conceição Miranda DD, Ribeiro ML, Pedrazzoli J Jr, Gambero. Attenuation of colitis injury in rats using Garcinia cambogia extract. A. Phytother Res. 2008 Oct 31. Published online ahead of print.

L-Ornithine May Reduce Fatigue in Females

Daily supplementation with the amino acid ornithine may reduce symptoms of fatigue, a new study has found.In the double-blind, placebo-controlled study, 17 healthy volunteers were randomized to receive L-ornithine (2,000 mg/day) for 7 days and 6,000 mg/day for 1 day or a placebo for 8 days. During the study, researchers induced physical fatigue in the subjects by having them perform a physical task consisting of workload trials on a cycle ergometer for two hours on two occasions.

The study authors found that in female participants given ornithine, the subjective feeling of fatigue was significantly lower compared with the placebo group. Female subjects taking the amino acid also performed better on the physical performance test compared to subjects receiving a placebo.

The amino acid also activated the urea cycle, which allows for the disposal of excess nitrogen. By increasing the disposal of nitrogen, ornithine was able to inhibit the increase in blood ammonia level caused by physical load. It is this increase in blood ammonia level that is in part responsible for the negative symptoms that occur after excessive exercise.

According to the researchers, “These results suggest that L-ornithine has an antifatigue effect by increasing the efficiency of energy consumption and promoting the excretion of ammonia. L-ornithine is a free amino acid and is not rich in meats or fish, so it is difficult to obtain amounts of L-ornithine from ordinary meals that would be sufficient to promote the antifatigue effect. We recommend L-ornithine intake as a nutritional supplement in cases of physical fatigue.”

Reference:

Sugino T, Shirai T, Kajimoto Y, Kajimoto O. l-Ornithine supplementation attenuates physical fatigue in healthy volunteers by modulating lipid and amino acid metabolism. Nutrition Research. November 2008. 28(11);738-743.

Nattokinase Supports Healthy Blood Pressure Levels

According to a recently published human trial, nattokinase can lower systolic and diastolic blood pressure, adding to the list of effects of a supplement known for its ability to reduce clotting and support blood vessel health.

The randomized, double-blind, placebo-controlled trial included 86 participants ranging from 20 to 80 years of age who had pre-hypertension or stage 1 hypertension. The subjects, who had an initial untreated systolic blood pressure of 130 to 159 mmHg, received a 2,000 unit capsule of nattokinase or a placebo for 8 weeks. Seventy-three subjects completed the study.

Compared with the control group, nattokinase lowered systolic blood pressure by 5.55 mmHg and diastolic blood pressure by 2.84 mmHg after the 8-week study. Nattokinase also resulted in a change in renin activity compared with the control group. Renin is an enzyme released into the bloodstream by kidney cells in response to decreasing sodium levels or low blood volume. Renin plays a role in the release of aldosterone, a hormone that helps control the body’s salt and water balance, and therefore renin is influential in controlling blood pressure levels.

The study authors concluded, “These findings suggest that increased intake of nattokinase may play an important role in preventing and treating hypertension.”

Reference:

Kim JY, Gum SN, Paik JK, Lim HH, Kim KC, Ogasawara K, Inoue K, Park S, Jang Y, Lee JH. Effects of nattokinase on blood pressure: a randomized, controlled trial. Hypertens Res. 2008 Aug;31(8):1583-8.

Galantamine Improves Cognitive Health of Parkinson’s Patients

In a new human trial, galantamine improved cognitive health and sleep quality in Parkinson’s patients with dementia.

In the open, controlled trial, 21 Parkinson’s patients with dementia were randomly divided into a group receiving 16 mg of galantamine per day and 20 patients were randomly divided into a control group. Cognitive, neuropsychiatric, and motor skills were assessed clinically before the trial and at 4, 12, and 24 weeks. To assess the subjects’ cognitive health, researchers used the Mini Mental State Examination (MMSE), the cognitive Alzheimer’s Disease Assessment Scale (ADAS-cog), the clock drawing test (a cognition test for dementia where the patient is asked to draw the face of a clock), the Frontal Assessment Battery (which is used to detect frontotemporal dementia), and the Neuropsychiatric Inventory.

Patients using galantamine had better scores on the Mini Mental State Examination, the Alzheimer’s Disease Assessment Scale, the clock drawing test and the Frontal Assessment Battery at the end of the study period as compared with the control group. Changes in total point scores on the Neuropsychiatric Inventory at the end of weeks 12 and 24, as compared with the beginning of the trial, were in favor of the group given galantamine. Specifically, galantamine use resulted in significant reductions in hallucinations, anxiety, sleep disturbance, and apathy. Galantamine also was accompanied by improvements in daily activity. Furthermore, improvements in gait and decreases in freezing and falls were seen in the galantamine group, although two patients of this group showed minor increases in tremor.

Reference:

Litvinenko IV, Odinak MM, Mogil’naya VI, Emelin AY. Efficacy and safety of galantamine (reminyl) for dementia in patients with Parkinson’s disease (an open controlled trial). Neurosci Behav Physiol. 2008 Oct 31.

N-Acetyl Cysteine Reduces Recurrent Pregnancy Loss

By virtue of its antioxidant abilities, N-acetyl cysteine (NAC) may reduce the incidences of recurrent miscarriages, suggests a new human study.

In women who are prone to frequent miscarriages, it has been suggested pregnancy could be associated with a state of oxidative stress that could initiate a cascade of changes that may lead to miscarriages. Because NAC is a powerful antioxidant, researchers set out to determine whether it can suppress the oxidative stress in pregnancy and whether it could stop miscarriages in women with unexplained recurrent pregnancy loss (RPL).

A group of 80 patients with a history of recurrent unexplained pregnancy loss were treated with 0.6 grams of NAC plus 500 mcg/day of folic acid. This group of patients was compared to an aged-matched group of 86 patients treated with 500 mcg/day of folic acid without NAC.

Results indicated that NAC plus folic acid compared with folic acid alone significantly increased the rate of continuation of a living pregnancy up to and beyond 20 weeks. NAC plus folic acid was associated with a significant increase in the take-home baby rate as compared with folic acid alone.

The researchers concluded that NAC is well-tolerated and that it “could be a potentially effective treatment in patients with unexplained RPL.”

Reference:

Amin AF, Shaaban OM, Bediawy MA. N-acetyl cysteine for treatment of recurrent unexplained pregnancy loss. Reprod Biomed Online. 2008 Nov;17(5):722-6.

Melatonin Improves Sleep in Night-Shift Workers

Researchers have found that night shift workers who take melatonin prior to bedtime are able to fall asleep faster compared to when melatonin is not used.

People who work nights often suffer from disturbed sleep and wakefulness. Circadian rhythm sleep disorders experienced by night workers are characterized by complaints of insomnia and excessive daytime sleepiness.

In the new double-blind, randomized, placebo-controlled, crossover study, researchers evaluated the effect of oral intake of 5 mg melatonin taken 30 minutes before bed time in 86 shift-worker nurses aged 24 to 46 years. The study authors evaluated the subjects’ insomnia, how long it took participants to fall asleep, number of awakenings, and sleep duration. Subjects were first given the melatonin, then remained free of any treatment for four days before being switched to the group receiving a placebo. Each participant completed a questionnaire immediately after awakening.

When the subjects were taking melatonin, they fell asleep faster compared to when the study started and compared to when they were taking a placebo. There was no evidence that melatonin altered total sleep time (as compared with baseline total sleep time). No adverse effects of melatonin were noted during the treatment period.

The researchers concluded, “Melatonin may be an effective treatment for shift workers with difficulty falling asleep.”

Reference:

Sadeghniiat-Haghighi K, Aminian O, Pouryaghoub G, Yazdi Z. Efficacy and hypnotic effects of melatonin in shift-work nurses: double-blind, placebo-controlled crossover trial. J Circadian Rhythms. 2008 Oct 29;6(1):10.

Selenium May Reduce First Signs of Metabolic Syndrome in Healthy Adults

Higher intakes of selenium in healthy young adults are linked to reduced levels of a marker related to the metabolic syndrome, suggest the results of a new study.

Metabolic syndrome is characterized by central obesity, hypertension, and disturbed glucose and insulin metabolism. It has been linked to increased risks of both type 2 diabetes and cardiovascular disease. Serum complement factor 3 (C3) has been found to be a marker for increased risk of the metabolic syndrome and can be used as a way to evaluate a person’s risk of developing the syndrome.

Researchers studied 100 healthy young adults between the ages of 18 – 34 with an average body mass index (BMI) of 21.6 kg. The scientists analyzed various lifestyle factors, measured blood pressure levels, and took fingernail samples to evaluate selenium concentrations. The researchers also measured C3 levels in the participants’ blood samples.

The results indicated that higher C3 levels were linked to higher BMI and waist circumference and higher levels of blood glucose and triglycerides. On the other hand, higher selenium levels measured from the fingernails were associated with lower C3 concentrations.

After calling for larger trials to confirm their findings, the researchers noted, “These findings suggest a possible role for selenium intake in the modulation of C3, whose assessment may be an early marker of metabolic syndrome manifestations.”

Reference:

Puchau B, Zulet MA, González de Echávarri A, Navarro-Blasco I, Martínez JA. Selenium intake reduces serum C3, an early marker of metabolic syndrome manifestations, in healthy young adults. Eur J Clin Nutr. 2008 Nov 5. Published Online Ahead of Print.

Hawthorn Strengthens Heart Health

Researchers have found that hawthorn (Crataegus) extract may reduce the risk of sudden cardiac death in patients who have moderately compromised left ventricular function.

To investigate the efficacy and safety of hawthorn as an adjunct treatment in patients with congestive heart failure, researchers conducted a randomized, double-blind, placebo-controlled study. The study included 2,681 adults with New York Heart Association class II or III chronic heart failure and who had reduced left ventricular ejection fraction (LVEF) 35 percent of below. The subjects received 900 mg per day of hawthorn extract or a placebo for 24 months.

When researchers looked at the group as a whole, there was no difference in the time to the first cardiac event and no difference in mortality rate between the placebo and hawthorn groups. However, when researchers looked at a subgroup of the patients with moderately reduced left ventricular function (operating at 25 to 35 percent capacity), hawthorn reduced sudden cardiac death by 39.7 percent. The hawthorn extract also demonstrated a high degree of safety in this group of patients, who were receiving medication for heart failure.

The researchers concluded that the data may indicate hawthorn “can potentially reduce the incidence of sudden cardiac death, at least in patients with less compromised left ventricular function.”

Reference:

Holubarsch CJ, Colucci WS, Meinertz T, Gaus W, Tendera M. The efficacy and safety of Crataegus extract WS(R) 1442 in patients with heart failure: The SPICE trial. Eur J Heart Fail. 2008 Nov 17. Published Online Ahead of Print.

Hawthorn is available in the CardioCare formula and is also available as a stand alone supplement.