Price range:  1-2 containers: $22.50 each.    3-5: $21.50   6+: $19.50

 

Eye & Vision Care is a comprehensive nutritional support product for healthy eyes. The formula contains a powerful blend of vitamins, minerals, herbs and trace elements which provide anti-oxidant defenses and essential nutrients to the eyes.

More than any other tissue in the body, the ocular lens and retina are continually exposed to oxygen and intense light radiation. Both light and oxygen can cause excess creation of free radicals.

Free radicals are naturally occuring molecules, but they can build up to toxic levels and cause degeneration of cells and tissues. Researchers believe that free radical damage may be a leading cause of aging and diseases such as cancer, heart disease, and dementia.

In the eyes, uncontrolled generation of free radicals can ultimately lead to macular degeneration, a condition leading to blindness and cataracts. Ocular tissues require a strong antioxidant defense system to protect them from free radical damage.

Eye & Vision Care is formulated to provide a unique combination of antioxidant nutrients that research has found to be important for healthy eyes. The product includes nutritionally meaningful amounts of lutein, beta-carotene, antioxidant vitamins, the trace element zinc, the cellular antioxidant N-Acetyl-L-Cysteine, the amino acid taurine, and potent antioxidants called flavonoids from bilberries and grape seeds.

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THE INGREDIENTS IN EYE & VISION CARE:

LUTEIN is a carotenoid similar to beta-carotene.  Recent research has shown that lutein is the major eye pigment of the outer retina. Lutein is especially concentrated in the rods, which are the visual cells of the retina that are responsible for black and white vision in the dark. The rods are especially susceptible to free radical damage because of their sensitive cell membranes. Lutein is a potent antioxidant, and researchers believe that the rods require it to protect themselves from light-induced free radical damage.
 
Lutein occurs naturally in the diet, especially in dark green leafy vegetables, broccoli, and kale. Most people derive about 1 to 2 mg of lutein daily from their diets.  Studies have shown that daily lutein intakes of 5 to 15 mg may be more appropriate for maintaining normal eye function during aging. As a result, Eye and Vision Care is formulated to provide 20 mg of natural lutein complex daily in each capsule.

BETA-CAROTENE serves at least two purposes for the eyes.  It is a valuable source of vitamin A which functions in the rod cells as a light receptor. Beta-Carotene is also an important antioxidant in the lens and retina.  According to the University of Maryland Medical Center, Beta-Carotene may also be used to ease sun sensitivity and to treat scleroderma.  Eye & Vision Care delivers 25,000 International Units of beta-carotene in each vegetarian capsule to ensure a reliable supply of this important eye nutrient.

BILBERRY EXTRACTis derived from the Bilberry shrub, a northern European cousin of North American blueberries, are a rich source of anthocyanosides, a class of flavonoids (plant pigments) recognized for their importance in eye health. Bilberry anthocyanosides are potent antioxidants in the visual cells of the retina, and help maintain normal blood flow in the fine capillary blood vessels that nourish the eyes and other tissues.  Bilberry is also an anti-inflammatory.  It can be used as a treatment for diarrhea and applied to the skin to heal wounds.  Each capsule of Eye & Vision Care contains 80 mg of a standardized 25 % anthocyanoside extract made from ripe Swedish bilberries.


QUERCETIN protects the gastro-intestinal tract from legions, oxidation, and allergens. Studies show that quercetin may even lower the risk of lung cancer (see below). As an anti-oxidant, quercetin prevents dangerous buildups of LDL cholesterol in the cardiovascular system.  This can reduce the risk of heart attack and the risk of death in case of a heart attack.  Macular degeneration, a wearing down of the eyes, is also thought to be caused by free radicals.  Quercetin may help fight this process as well. 

In addition, people with arthritis have experienced some relief while taking quercetin supplements, as it may reduce the type of inflammation which causes joint pain.Quercetin’s anti-oxidant properties work in several ways.  First, quercetin prevents the oxidation of lipids by free radicals.  The gastro-intestinal tract is at especially high risk of damage from free radicals because of its low pH level.  However, the section of the GI tract called the lipid bilayer, comprised of cell walls, is a vitally important part of the body’s immune system.  Quercetin protects the lipids that make up the cell walls of the gastro intestinal tract, thereby supporting a strong immune response.


ZINC is essential for normal visual signal transmission in the retina. Zinc is part of many of the enzymes involved in vitamin A-dependent light reactions in the rod cells. Moreover, zinc is an essential part of the process that removes potentially dangerous superoxide radicals in the visual cells, the lens, and other tissues. Each capsule of Eye & Vision Care provides 25 mg of zinc in its most easily absorbable form.

N-ACETYL-L-CYSTEINE (NAC), on the other hand, easily enters the cell and is used to allow glutathione to pass through the cell wall. NAC also appears to have antioxidant properties itself. Many studies have shown that ocular glutathione levels decline as we age. Dietary supplementation with both glutathione and NAC may help maintain normal extracellular and intracellular glutathione levels. Eye & Vision Care provides 200 mg of NAC per capsule.

TAURINE a sulfur amino acid, is the most abundant free amino acid in ocular tissues, where it functions as a stabilizer, antioxidant, regulator, and neurotransmitter.  Taurine is important in maintaining normal extra- and intracellular distribution of calcium and other nutrients.  Eye & Vision Care provides 400 mg of pure taurine.

GRAPE SEED EXTRACT is rich in proanthocyanidins, another group of important flavonoids. Proanthocyanidins are highly regarded for their strong antioxidant properties and their role in supporting the body’s capillary blood vessel system.  Each capsule of Eye & Vision Care contains 100 mg of high quality European grape seed extract (from Vitis vinifera) with a minimum of 92% proanthocyanidins.

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SUPPORTING RESEARCH:

Lutein and its Role in Eye Disease Prevention

National Eye Institute, December 2006
National Institutes of Health

Claims made about an association between lutein and eye health are speculative and should be viewed with caution. The possible benefits of lutein for the eye remain uncertain.

Certain foods contain antioxidants -- molecules that can help maintain healthy cells and tissues in the eye. One category of these antioxidants, called carotenoids, may play a role in maintaining eye health as well as overall health. One of these carotenoids -- lutein -- is concentrated in the retina and lens of the eye.

There is little definitive scientific evidence at this time to support claims that taking supplements containing lutein can decrease the risk of developing advanced age-related macular degeneration (AMD), a blinding eye disease, or cataract. However, a number of studies intended to examine trends in a population -- and not hard medical evidence -- suggest a link between lutein and decreased risk of eye disease:

• In 1994, a National Eye Institute (NEI)-supported study indicated that consumption of foods rich in carotenoids -- particularly green, leafy vegetables such as collard greens, kale, and spinach -- was associated with a reduced risk of developing AMD.1
• In 1999, data from the Nurses Health Study showed a reduced likelihood of cataract surgery with increasing intakes of lutein and another carotenoid --zeaxanthin. 2
• In 1999, the Health Professionals Follow-up Study found a trend toward a lower risk of cataract extraction with higher intakes of lutein and zeaxanthin. 3
• In 1999, a follow-up to an NEI-supported population-based study -- called the Beaver Dam Study -- concluded that people with diets higher in lutein and zeaxanthin had a lower risk of developing cataract. 4
• In 2001, data from the Third National Health and Nutrition Examination Survey reported that higher intakes of lutein and zeaxanthin among people ages 40-59 may be associated with a reduced risk of advanced AMD. 5

Conversely, in 1998, the Beaver Dam Study found no significant association between the risk of either early or advanced AMD in groups that had either the highest intakes of lutein and zeaxanthin or the lowest intakes of lutein and zeaxanthin. The study researchers caution that generally, the consumption of lutein and zeaxanthin in this population may have been too low to have had an impact on the risk of AMD. 6,7

These conflicting data make it clear that the relationship between lutein and eye health needs to be examined more closely before conclusions can be drawn.

So What's Next for Lutein?

The NEI is investigating the role of nutrition -- including the effects of lutein -- in eye disease. Specifically, the NEI is:

• Conducting a pilot study to see how well lutein is absorbed into the bloodstream in people over age 60. This is a first step in testing this substance as a possible treatment for AMD. The pilot study is not designed to treat AMD; its purpose is to help determine the best dose of lutein oral supplements in people over age 60. This dose of lutein can then be separately tested in humans as a possible treatment for AMD.
  
  
• Supporting a study that compares the intake of lutein and zeaxanthin with the likelihood of developing AMD and/or cataract. Researchers explain that results from this study -- called the Carotenoids and Age-Related Eye Disease in Women's Health Study -- will help health professionals make dietary recommendations regarding the benefit of eating diets rich in lutein and zeaxanthin. Study results will also provide information needed to conduct clinical trials that can evaluate the effectiveness of lutein and zeaxanthin supplements on the progression of age-related eye disease. 

The Role of Nutrition in Eye Disease Prevention
In October 2001, the NEI published the results of a seven-year study -- called the Age-Related Eye Disease Study (AREDS) -- that showed that a high-dose combination of vitamin C, vitamin E, beta-carotene, and zinc significantly reduces the risk of developing advanced stages of AMD by about 25 percent. These high levels of antioxidants and zinc are the first effective treatment to slow the progression of AMD. The nutrients are not a cure for AMD, nor will they restore vision already lost from the disease. But they are playing a vital role in helping people at high risk for developing advanced AMD keep their vision. In the same study, the antioxidant and zinc combination showed no significant effect on the development or progression of cataract.
Lutein was not part of this study because during the AREDS planning stages in the early 1990s, lutein and zeaxanthin were not commercially available.

---

1 Seddon, Johanna M., MD, et al, "Dietary Carotenoids, Vitamins A, C, and E, and Advanced Age-Related Macular Degeneration," JAMA, Vol. 272, No. 18, November 1994, pgs. 1413-1420.
2 Chasen-Taber et al., "A Prospective Study of Carotenoid and Vitamin A Intakes and Risk of Cataract Extraction in US Women," American Journal of Clinical Nutrition, 1999, Vol. 70, pgs. 509-516.
3 Brown et al., "A Prospective Study of Carotenoid Intake and Risk of Cataract Extraction in US Men," American Journal of Clinical Nutrition, 1999, Vol. 70, pgs. 517-524.
4 Lyle et al., "Serum Carotenoids and Tocopherols and Incidence of Age-Related Nuclear Cataract," American Journal of Clinical Nutrition, 1999, Vol. 69, pgs. 272-277.
5 Mares-Perlman et al., "Lutein and Zeaxanthin in the Diet and Serum and Their Relation to Age-Related Maculopathy in the Third National Health and Nutrition Examination Survey," American Journal of Epidemiology, 2001, Vol. 153, No. 5, pgs. 424-432.
6 Mares-Perlman et al., "Association of Zinc and Antioxidant Nutrients With Age-Related Maculopathy," Archives of Ophthalmology, 1996, Vol. 114, No. 8, pgs. 991-997.
7 VandenLangenberg et al., "Associations Between Antioxidant and Zinc Intake and the 50-Year Incidence of early Age-Related Maculopathy in the Beaver Dam Eye Study," American Journal of Epidemiology, 1998, Vol. 148, No. 2, pgs. 204-14.

Studies:

“Supplementation with the carotenoids lutein or zeaxanthin improves human visual performance.”

Kvansakul,-J; Rodriguez-Carmona,-M; Edgar,-D-F; Barker,-F-M; Kopcke,-W; Schalch,-W; Barbur,-J-L. Ophthalmic-Physiol-Opt. 2006 Jul; 26(4): 362-71

BACKGROUND: Macular pigment (MP) is found in diurnal primate species when vision spans a range of ambient illumination and is mediated by cone and rod photoreceptors. The exact role of MP remains to be determined. In this study we investigate two new hypotheses for possible MP functions.

OBJECTIVE: As MP absorption coincides partly with that of rhodopsin, MP may reduce rod signal effectiveness in the mesopic range, thus extend the usefulness of cone-mediated vision into the mesopic range. Forward light scatter in the eye can reduce retinal image contrast. If blue light contributes significantly to intraocular scatter, selective blue light absorption by MP could reduce the effects of scatter.

DESIGN: We investigated 34 subjects from a carotenoid supplementation trial. The measurements included high mesopic contrast acuity thresholds (CATs), macular pigment optical density (MPOD), wavefront aberrations, and scattered light. The measurements were made after 6 months of daily supplementation with zeaxanthin (Z, OPTISHARP), lutein (L), a combination of the two (C), or placebo (P), and again after a further 6 months of doubled supplementation.

RESULTS: The data reveal a trend toward lower CATs in all groups supplemented, with a statistically significant improvement in the lutein group (p = 0.001), although there was no correlation with MPOD. Light scattering in the eye and the root-mean-square wavefront aberrations show decreasing trends as a result of supplementation, but no correlation with MPOD.

CONCLUSIONS: The results suggest that supplementation with L or Z increases MPOD at the fovea and at 2.5 degrees , and that supplementation can improve CATs at high mesopic levels and hence visual performance at low illumination.

BETA-CAROTENE

 

“Protective effects of tomato extract with elevated beta-carotene levels on oxidative stress in ARPE-19 cells.”

Chichili,-G-R; Nohr,-D; Frank,-J; Flaccus,-A; Fraser,-P-D; Enfissi,-E-M; Biesalski,-H-K. Br-J-Nutr. 2006 Oct; 96(4): 643-9

Epidemiological studies show that dietary products rich in carotenoids delay the progression of age-related macular degeneration. Experimental evidence from cellular studies on the antioxidant actions of carotenoids in the retinal pigment epithelium is still, however, fragmentary. The present study examined the uptake and protective potential of dietary carotenoids from tomato on the human retinal pigment epithelial cell line ARPE-19. ARPE-19 cells were incubated in medium supplemented with tomato extract containing high levels of beta-carotene, lycopene and traces of lutein. The cellular uptake of carotenoids was analysed by reverse-phase HPLC. Oxidative stress was induced by treatment with 1 mm-H2O2. Nitrotyrosine was detected by immunocytochemistry, and oxidised proteins (protein carbonyls) were measured by a quantitative ELISA method. Lipid peroxidation was assessed by quantifying thiobarbituric acid reactive substances. ARPE-19 cells preferentially accumulated lutein and beta-carotene rather than lycopene. Nitrotyrosine formation was considerably reduced in cells incubated with tomato extract compared with controls after H2O2 treatment. Protein carbonyls were reduced by 30 % (P = 0.015), and the formation of thiobarbituric acid-reactive substances was reduced by 140 % (P = 0.003) in cells incubated with tomato extract. The present study provides the experimental evidence for protective effects of dietary tomatoes rich in carotenoids on oxidative stress in the retinal pigment epithelium.

“Antioxidant activity, mutagenicity/anti-mutagenicity, and clastogenicity/anti-clastogenicity of lutein from marigold flowers.”

Wang,-M; Tsao,-R; Zhang,-S; Dong,-Z; Yang,-R; Gong,-J; Pei,-Y. Food-Chem-Toxicol. 2006 Sep; 44(9): 1522-9

High dietary intake of lutein has been associated with risk reduction of many chronic diseases, including age-related macular degeneration (AMD), cancer, and cardiovascular diseases. Lutein in food is generally regarded as safe. However, information on the toxicological and beneficial effect of lutein at higher doses is limited. In this study, large amount of lutein was extracted and purified from marigold flower (Tagetes erecta L.). The antioxidant activity of lutein was examined by using the photochemiluminescence (PCL) assay and the beta-carotene-linoleic acid model system (beta-CLAMS). Lutein showed a greater antioxidant activity than the other two common carotenoids, beta-carotene and lycopene. The mutagenicity and anti-mutagenicity of lutein at 334, 668 and 1335 microg/plate were examined using the standard Ames test in the presence and absence of S9 mix. Lutein was not only found to be non-mutagenic at all doses, but it showed an anti-mutagenic effect in a dose-dependent manner. Similar results were found in a chromosome aberration test using Chinese hamster ovary cells for the evaluation of clastogenicity and anti-clastogenicity of lutein at 66.8, 133.5 and 267.0 mg/L. Our findings provided scientific evidence for the safe use and health beneficial effects of lutein.

“Low levels of carotenoids and retinol in involutional osteoporosis. “

Maggio,-D; Polidori,-M-C; Barabani,-M; Tufi,-A; Ruggiero,-C; Cecchetti,-R; Aisa,-M-C; Stahl,-W; Cherubini,-A. Bone. 2006 Feb; 38(2): 244-8

Previous epidemiological studies conducted in retinol-supplemented subjects showed an association between high serum levels or dietary intake of retinol and risk of hip fracture. On the other side, observational studies revealed that non-supplemented subjects with higher dietary intake of retinol lose less bone with age than subjects with lower intake. This discrepancy, currently unexplained, suggests that nutrition plays a major role in conditioning the effects of retinol on bone. Since retinol is derived from both retinoids--contained in animal food--and carotenoids--contained in vegetables and fruits--we evaluated a possible role of carotenoids in involutional osteoporosis. Therefore, plasma levels of beta-carotene and other carotenoids, in addition to those of retinol, were measured in free-living, non-supplemented, elderly women with or without severe osteoporosis. Plasma levels of retinol and of all carotenoids tested, with the exception of lutein, were consistently lower in osteoporotic than in control women. A weak association was found only between retinol and femoral neck bone mineral density in osteoporotic women. Our study suggests a bone sparing effect of retinol, to which the provitamin A activity of some carotenoids might have contributed.

"Antioxidant supplements improve parameters related to skin structure in humans. “

Heinrich,-U; Tronnier,-H; Stahl,-W; Bejot,-M; Maurette,-J-M. Skin-Pharmacol-Physiol. 2006; 19(4): 224-31

In the present study we investigated the influence of two different antioxidant supplements composed of carotenoids, vitamin E and selenium on parameters related to skin health and skin aging. Thirty-nine volunteers with healthy, normal skin of skin type 2 were divided into 3 groups (n = 13) and supplemented for a period of 12 weeks. Group 1 received a mixture of lycopene (3 mg/day), lutein (3 mg/day), beta-carotene (4.8 mg/day), alpha-tocopherol (10 mg/day) and selenium (75 microg/day). Group 2 was supplemented with a mixture of lycopene (6 mg/day), beta-carotene (4.8 mg/day), alpha-tocopherol (10 mg/day) and selenium (75 microg/day). Group 3 was the placebo control. Upon supplementation serum levels of selected carotenoids increased in both verum groups. Skin density and thickness were determined by ultrasound measurements. A significant increase for both parameters was determined in the verum groups. Roughness, scaling, smoothness and wrinkling of the skin were determined by Surface Evaluation of Living Skin (Visioscan). Roughness and scaling were improved by the supplementation with antioxidant micronutrients. In the placebo group no changes were found for any of the parameters. Copyright (c) 2006 S. Karger AG, Basel.

 

Bilberry Extract (Vaccinium myrtillus):

Studies on Vaccinium myrtillus anthocyanosides. I. Vasoprotective and antiinflammatory activity

Lietti A, Cristoni A, Picci M.

A Vaccinium myrtillus anthocyanosides preparation (equivalent to 25% of anthocyanidins) demonstrated significant vasoprotective and antioedema properties in exerimental animals. In rabbits, the skin capillary permeability increase, due to chloroform, was reduced both after i.p. (25--100 mg/kg) and oral administration (200--400 mg/kg) of anthocyanosides. Their activity was more lasting in comparison to rutin or mepyramine and this did not seem to be due to a specific antagonism towards inflammatory process mediators such as histamine or bradykinin. Experiments carried out in rats demonstrated that Vacinium myrtillus anthocyanosides were effective both in skin capillary permeability test as well as on vascular resistance of rats fed a P factor deficient diet. In the former test effective doses were in the range of 25--100 mg/kg (by oral route). In both the animal species investigated, anthocyanosides were two-fold more active when compared to the flavonoid rutin. Vaccinium myrtillus anthocyanosides by oral route inhibited carrageein paw oedema in rats showing a dose-response relationship. An antioedema activity was detected also after i.v. or topical application.

PMID: 9100

The Historical Use of Bilberries:
 
Bilberry (Vaccinium myrtillus) is a perennial shrub native to Northern Europe, Northern America, and Canada. The plant grows up to half a meter tall and has small dark leathery leaves and produces a fruit similar to the American blueberry. A member of the Ericaccae or Heath family, it is also known by the common names huckleberry and whortleberry.
  

Tinctures and teas made from bilberry leaves have been consumed as food for centuries by many cultures in China and Europe. Their health benefits have traditionally been associated with the eyes and the urinary system.
 
Bilberries are a common traditional food and medicine of many Native American Indians. Some tribes still harvest them as a winter food source.
 
Bilberry jam has been popular in Britain for hundreds of years, and during World War II British pilots took it because they believed it improved night vision and reduced visual fatigue.
 
How Bilberry Works:
 
Scientific research has found that bilberry contains biologically powerful substances known as anthocyanosides, which are responsible for the red, blue or violet colors in flowers and fruits. Evidence suggests that antho-cyanosides strengthen the walls of blood vessels, reduce inflammation, and generally stabilize all tissues containing collagen. Collagen is the main protein in the fluid matrix of the eye, and if it breaks down disease often follows. The eye muscles, which keep the eye in its correct shape, also require healthy collagen. Bilberry's anthocyanosides in particular have been found to interact with the eye.
 
Like most herbal medicines, positive effects obtained from the plant are not necessarily attributed to only one chemical component. At least twelve different phenolic acids help to contribute to bilberry's beneficial effects.
 
Recent research on Anthocyanins:
 
There is a growing body of clinical and traditional information on the positive effects of anthocyanins. Because bilberries are such an excellent source of anthocyanins, they are the subject of many scientific and clinical studies. Much research focuses on the ability of anthocyanins to strengthen and stabilize collagen. Collagen is an essential component of all connective tissue, including the thousand of tiny capillaries of the eye. Healthy capillaries reduce leakage and improve blood and oxygen delivery to the eye.  Collagen is the main protein in the fluid matrix of the eye: if it breaks down, disease often follows. The eye muscles, which keep the eye in its correct shape, also require healthy collagen.
 
The antioxidant capabilities of anthocyanins could have a role to play in the prevention of macular degeneration and cataract formation, both of which are thought to be linked to free radical damage. Other studies document the effect of anthocyanins on night vision. Research on anthocyanins is also producing promising results in many other areas of health care.
 
Optimal health requires quality food supplements. Consider the superior features of Flora•Vision and make the quality choice.

 

Recommended reading for more information:
 
1. McCaleb, R. Bilberry: herbal antioxidant ripe for the picking, Better Nutrition, November 1994, 56-60.
 
2. Murray M. Bilberry (Vaccinium myrtillus), American Journal of Natural Medicine, 4 (1): 18-22 (1997).
 
3. Belleoud, L. et al. Study on the effects of anthocyanin glucosides on the nocturnal vision of air traffic controllers, Revue de Medecine Aeronautique et Spatiale, No. 18, June 16, 1966. 210=Bravetti, G.O. et al. Preventive medical treatment of senile cataract with Vitamin E and Vaccinium myrtillus anthocyanosides: clinical evaluation, Ann Ottalmol Clin Ocul, 115:109-116 (1989).
 
4. Havsteen B. Flavonoids, a class of natural products of high pharmacological potency. Biochem Pharmacol 32: 1141<1148, 1983.
 
5. Gabor M. Pharmacologic effects of flavonoids on blood vessels. Angiologica 9: 355<374, 1972.
 
6. Mian E, et al. Anthocyanosides and the walls of microvessels: Further aspects of the mechanism of action of their protective effect in syndromes due to abnormal capillary fragility. Minerva Med 68: 3565<3581, 1977. 
 
7. Wegmann R, et al. Effects of anthocyanosides on photo receptors. Cyto-enzymatic aspects. Ann Histochim 14: 237<256, 1969.
 
8. Cluzel C, Bastide P, Wegman R, et al. Enzymatic activities in the retina and anthocyanosides extracted from Vaccinium myrtillus(lactate dehydrogenase, alpha-hydroxybutyrate dehydrogenase, 6-phosphogluonate dehydrogenase, glucose-6 phosphate dehydrogenase,alpha-glycerophosphate dehydrogenase, 5-nucleotide, and phosphoglucose isomerase) (translated from French). Biochem Pharmacol 19: 2295<2302, 1970.
 
9. Wegmann R, et al. Effects of anthocyanosides on photo receptors. Cyto-enzymatic aspects. Ann Histochim 14: 237<256, 1969.
 
10. Bone K. et al. Mediherb Professional review 59(3):1007.
 
11. Bone K, et al. Mediherb Professional Review 59(3): 1997.
 
12. Bettini, V. et al. Effects of Vanninium mytrillus anthocyanosides on vascular smooth muscle. Fitoterapia v55, 1984
 
13. Lobay, D., ND. The Therapeutic Effect of Bilberry, Country Health Magazine, Spring 1993.
 
14. Detre, A. et al. Studies on vascular permeability in hypertension: action of anthocyanosides. Clinical Physiological. Biochemistry. V4, 1986.
 
15. Flynn, M.S. et al. Your Guide to Standardized Herbal Products, One World Press, 1995.
 
16. Jayle, G.E. et al. Étude concernant l'action sur la vision nocturne des anthocyanosides extraits de Vaccinium myrtillus. Annales d'Oculistique, v198, June 1965.
 
17. Colantuoni, A. et al. Effects of Vaccciniummyrtillus anthocyanosides on arterial vasomotion. Arzneimittel-Forschung, v41, Sept. 1991.


ZINC:

Zinc Helps Kids Grow
By Jennifer Warner, WebMD Medical News

May 24, 2002 -- Some infants and children may benefit from adding zinc to their diets. New data suggest that increasing the amount of this mineral may help children reach a healthy height and weight.

"Because of the important functional consequences of zinc deficiency for children's growth and other health outcomes, interventions to improve zinc ... [in the diet] should be considered in those populations at particularly high risk of zinc deficiency," write the authors of a report published in the June issue of the American Journal of Clinical Nutrition.

Zinc is a mineral found in a variety of foods such as red meat, whole-grain breads and cereals, dried beans, and seafood. It is also found in small amounts in breast milk.

Zinc is vital for the normal growth and development of the reproductive organs and brain and plays a role in the normal functioning of the immune system and many other processes in the body. Recently, zinc deficiency has been linked to decreased growth, increased colds and infections, impaired memory, learning disabilities, and poor attention span. The deficiency is a major problem in developing countries; for instance, 70% of school age children in Thailand are deficient in zinc.

In the U.S., zinc deficiency in children is not well recognized, although it affects an estimated 6% of girls and 10% of boys overall. Disadvantaged children are especially at risk -- more than 50% of poor children and 30% of non-poor children aged 1-5 get less than 70% of the Recommended Dietary Allowance of zinc (10 milligrams per day for children). In fact, recent data suggest that of 16 key nutrients, more children were deficient in zinc than in any other nutrient.

This new report looked at 33 studies on the effects of zinc supplementation on children up to 10 years old that were published between 1976 and 2001.

Overall, zinc supplementation produced very significant positive effects on both height and weight measures of the children. And the effect was even greater among children who already suffered from stunted growth or were underweight.

Researchers say it is hard to quantify the impact because the effects vary according to the age of the child, duration of supplementation, and other factors. But they cite the example of a Guatemalan study that found three years of zinc supplementation (from 3 to 36 months of age) was responsible for nearly an inch in additional growth.

Currently, scientists do not believe there is enough data to recommend widespread zinc supplementation in U.S. children as other studies of zinc's benefits have been inconclusive. In addition, scientists are unsure as to how much is enough; too much zinc can be as dangerous as a deficiency.

Adequate zinc can be obtained thorough a well-balanced diet of a variety of foods. Those foods include red meat, nuts, shellfish, potatoes with skins, beans, and mushrooms.
© 2002 WebMD Inc. All rights reserved.

Have a Cold? Think About Zinc
By Roxanne Nelson, WebMD Medical News, Reviewed By Merle Diamond, MD

Aug. 14, 2000 -- Sneezes, sniffles, that all over blah, achy feeling ... the average American gets between two and six colds a year, and so far, treatments have been ineffective at snuffing them out. But now researchers have found that zinc lozenges may actually cut the time spent suffering from a cold and lessen the symptoms.

In a study that appears in the current issue of the Annals of Internal Medicine, researchers from Wayne State University in Michigan found that patients who took zinc lozenges recovered almost twice as quickly as those who took a placebo. These findings fly in the face of at least five previous trials that didn't show a beneficial effect of zinc.

Led by Ananda Prasad, MD, PhD, a professor of medicine at Wayne State University, the researchers gave either zinc lozenges or a placebo to 48 individuals who had come down with cold symptoms within the previous 24 hours. Each person had to have at least two standard cold symptoms, such as sneezing, sore throat, fever, cough, and muscle aches.

The colds of patients taking the zinc lozenges lasted an average of four and a half days, while the colds of those taking the placebo had symptoms for eight days. Coughing stopped in the zinc group in half the time of the placebo group, and runny noses cleared up about two days sooner.

Prasad acknowledges in the study that previous research has not had such encouraging results. He points out to WebMD, however, that certain problems in previous studies may account for the differences in results. Some of the studies, he says, may have used a type of lozenge that doesn't release the zinc properly when a person takes it in his mouth.

"The dosage also has to be adequate," Prasad says. "I think one study used half the dose that we did, and the zinc must be taken within 24 hours of symptom onset."

Ronald Turner, MD, doesn't think this study will have much impact on usage by the public at large. "The data on zinc treatment have been extremely inconsistent from study to study," he says. "And zinc has been available to the public for some time. The product is available as a dietary supplement, and usage is probably unrelated to physician recommendation." Turner, who was not involved in the study, is a professor of pediatrics at the Medical University of South Carolina, and he has done unrelated research on zinc.

In an editorial that accompanied the study, Norman Desbiens, MD, with the University College of Medicine in Chattanooga, questions whether the study was properly "blinded," meaning, were the participants completely unaware of whether they were taking the placebo or the zinc.

For the conclusions to be accurate, this is a very important issue in any study that uses a placebo to measure the effectiveness of a medication.

Turner agrees. "Inadequate blinding has been a consistent criticism of the zinc studies, and these authors do not appear to have adequately addressed the issue."

For example, the patients were asked to guess whether they were taking the placebo or the zinc. About half of those taking the zinc, and around a quarter taking the placebo, identified the lozenges correctly. But the researchers felt that these numbers were not high enough to negatively influence the results.

However, Desbiens feels the fact that more than three and a half times as many participants who received zinc correctly guessed that they were given zinc, may have affected the results of the study. "I suspect that the zinc and placebo had detectable differences, and therefore, a blind was not completely established," he writes.

Prasad writes that a test was done with healthy people who were given both types of lozenges, and it "showed that the zinc and placebo lozenges were indistinguishable in taste." He points out that none of the people involved in the study had ever previously used zinc lozenges, and in fact, they could not participate if they had used zinc in the past.

"This is the question I don't understand," Prasad tells WebMD, "how they would know if they've never had zinc or if they only taste one lozenge."

Everyone was only given one kind of lozenge -- either zinc or the placebo, he says, and they had no opportunity to taste the other kind. "It would be one thing if they had both kinds, but they didn't. So how would they be able to detect a difference in taste?"

The most common side effects from taking the zinc were a dry mouth and constipation. But since the amount of zinc that the study patients took is five times the current RDA of 15 mg, the researchers caution that zinc lozenges should not be taken for more than three days at a time. They recommend that if a person does not improve after three days of zinc treatment, then he should be evaluated for other type of respiratory illnesses or allergies.

Desbiens isn't convinced that taking zinc will help a cold, but the researchers disagree, saying their results show zinc can reduce the average duration and severity of the common cold.

"I think our results are very clear-cut," Prasad says. "The editorialist is saying that if they knew it was the zinc, it might have had an effect on their perception of whether or not they were getting better.

"But we measured symptoms," he adds. "It's hard to say you don't have symptoms if you're coughing or sneezing. Some of the people I recruited were physicians, and they're highly critical people and not easily convinced. So when they were cured in three days, they came to tell me and let me know."

The study was supported in part by an unrestricted grant from the George and Patsy Eby Research Foundation. George Eby holds patent rights to zinc lozenges and supplied both the zinc and placebo lozenges for this study. But Prasad writes the research funds were "unrestricted," and "the authors have neither industry connections nor personal financial conflicts of interest related to this study."  

© 2000 WebMD Inc. All rights reserved.

N-ACETYL-L-CYSTEINE:

The University of Maryland Medical Center:

Overview
Cysteine is an amino acid that can be found in many proteins throughout the body. N-acetyl-L-cysteine (NAC), a modified form of cysteine, helps break down mucus and detoxify harmful substances in the body. Both cysteine and NAC have been shown to increase levels of the antioxidant glutathione.

Antioxidants are substances that scavenge free radicals, damaging compounds in the body that alter cell membranes, tamper with DNA, and even cause cell death. Free radicals occur naturally in the body, but environmental toxins (including ultraviolet light, radiation, cigarette smoking, and air pollution) can also increase the number of these damaging particles.

Free radicals are believed to contribute to the aging process as well as the development of a number of health problems including heart disease and cancer. Antioxidants such as glutathione can neutralize free radicals and may reduce or even help prevent some of the damage they cause.

Uses
NAC offers a variety of potential therapeutic uses, particularly in the prevention or in the treatment of the following conditions:

Acetaminophen Poisoning
Healthcare practitioners commonly administer oral or intravenous NAC to prevent or reduce liver and kidney damage associated with overdoses of acetaminophen (also called paracetamol), an over the counter medication commonly used for pain or headache. Acetaminophen poisoning can occur at lower doses of the drug if someone drinks alcohol on a regular basis.

Heart Disease
In studies of people having a heart attack or those with ongoing chest pain, NAC, in combination with nitroglycerin (a drug that opens up blood vessels and improves blood flow), has been more effective than either NAC or nitroglycerin alone in reducing subsequent chest pain, heart attack, and the risk of death. However, individuals who receive both NAC and nitroglycerin may experience a severe headache. These results are promising, but further studies are needed to confirm the safety and effectiveness of NAC for heart disease.

Respiratory Illness
A review of scientific studies also found that NAC may help dissolve mucus and improve symptoms associated with chronic bronchitis, asthma, cystic fibrosis and emphysema. Chronic smokers also may benefit from NAC supplementation. Studies on large groups of people have found that NAC appears to have cancer prevention properties in people who are at risk for lung cancer.

Free radical damage is believed to contribute to the development and progression of acute respiratory distress syndrome (ARDS), a condition characterized by the rapid and progressive malfunction of the lungs. Although not all studies agree, some research of animals and people suggest that intravenous NAC may boost levels of glutathione and subsequently prevent and/or treat lung damage caused by ARDS. However, results of other studies have been conflicting. Further investigation is needed.

HIV/AIDS
HIV infection is considered to be a condition of excessive oxidative stress (caused by free radicals) where the antioxidant glutathione is depleted significantly. Therefore, it is believed that supplementation with cysteine may help strengthen the immune system in those with HIV and diminish the bodily damage associated with this infection.

In one well-designed study of people with HIV, those who took a daily supplement regimen including the amino acid glutamine (40 gram per day), vitamin C (800 mg), vitamin E (500 IU), beta-carotene (27,000 IU), selenium (280 mcg), and N-acetylcysteine (2400 mg) gained significantly more weight after 12 weeks than those who took placebo. Similarly, in a smaller-scale study using NAC in HIV positive patients, the supplement did increase glutathione levels while a placebo did not.

These studies and others support the theory that NAC may prove to be a useful addition to conventional medical care for those with HIV. Other studies, however, have shown negative results using NAC for those with HIV. Therefore, more research is needed before conclusions can be drawn about NAC supplements for this infection.

Other:
Low levels of cysteine may be linked to an increased risk of cervical dysplasia (changes to the opening of the uterus, that are precancerous or cancerous). Preliminary evidence also suggests that NAC supplements may:

---Improve symptoms associated with Sjogren's syndrome (an autoimmune disorder characterized by dry mouth and dry eyes)

---Enhance cognitive functioning in some individuals with Alzheimer's disease

---Prevent development of cataracts and macular degneration

---Slow down motor impairment in amyotrophic lateral sclerosis (ALS, often called Lou Gehrig's disease which is a progressive loss of control of voluntary muscles due to destruction of nerve cells in the brain and spinal cord)

---Help treat hepatitis C when combined with standard medical treatment

---Increase HDL cholesterol (the good kind of cholesterol).

---Further studies are needed to confirm these early findings.

Dietary Sources
The body synthesizes cysteine from the essential amino acid methionine. Cysteine is also found in most high-protein foods including ricotta, cottage cheese, yogurt, pork, sausage meat, chicken, turkey, duck, luncheon meat, wheat germ, granola, and oat flakes.

Available Forms
•             NAC aerosol spray (prescription)
•             NAC liquid solution (prescription)
•             NAC topical solution
•             L-cysteine powder
•             Cysteine/NAC tablets or capsules

How to Take It
NAC is administered either intravenously or orally in the hospital to treat acetaminophen (paracetamol) poisoning in both children and adults. Acetaminophen poisoning is a medical emergency and treatment must be started within eight hours of an overdose.

Pediatric
There is no specific pediatric recommendation for cysteine. If laboratory tests reveal that the child has an amino acid imbalance that requires treatment, a healthcare provider may recommend a complete amino acid supplement that contains cysteine.

Adult
Recommended adult doses of NAC vary depending on the health condition being treated. The following list provides guidelines for the most common uses.

Respiratory illness: 200 mg two times per day for chronic bronchitis. ARDS is a medical emergency and is treated in the intensive care unit in the hospital with intravenous NAC as part of a comprehensive treatment regimen.

Antioxidant protection/general health: 500 mg per day to start. Dosage may be increased, with expert guidance. Someone with HIV/AIDS may be put on a dose as high as 4,000 mg per day. Adding a multivitamin will ensure that you are getting the B vitamins you need when taking NAC.

Precautions
Because of the potential for side effects and interactions with medications, dietary supplements should be taken only under the supervision of a knowledgeable healthcare provider.

Some forms of cysteine are toxic and should be avoided. These include D-cysteine, D-cystine, and 5-methyl cysteine.

NAC may raise levels of homocysteine, an amino acid believed to play a role in the development of heart disease. Be sure to have your health care provider check your homocysteine level if you are taking NAC.

Extremely high doses (more than 7 grams) of cysteine should be avoided because it may be toxic to human cells and may even lead to death.

Oral NAC may cause nausea, vomiting, and diarrhea.

Intravenous administration of NAC (to treat, for example, acetaminophen poisoning) may cause severe allergic reactions, even angioedema (significant swelling of the soft tissue just beneath the skin including the face, lips, and around the eyes) or anaphylaxis (a life-threatening allergy that leads to inability to breath). Plus, there has been one case report of seizures from intravenous administration of NAC to a young girl for paracetamol intoxication.

Cysteine supplements should not be taken by individuals with cystinuria, a kidney condition in which excessive amounts of cysteine (along with three other amino acids) are lost in the urine.

Possible Interactions
If you are currently being treated with any of the following medications, you should not use cysteine supplements without first talking to your healthcare provider.

Blood Pressure Medications, Angiotensin-converting Enzyme (ACE) Inhibitors
NAC may enhance the blood pressure-lowering effects of ACE inhibitors, medications commonly used to treat high blood pressure. Examples of ACE inhibitors include benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, quenipril, ramepril, and trandolapril.

Immunosuppressive Medications
Treatment with NAC may enhance the effectiveness of immunosuppressive medications such as azathioprine, cyclophosphamide, prednisolone, or prednisone. More research in this area is needed.

Cisplatin and Doxorubicin
Laboratory and animal studies have suggested that NAC may reduce the toxic effects associated with both cisplatin and doxorubicin, medications used to treat a variety of cancers. However, scientific studies are needed to see if these effects apply to people.

Nitroglycerin and Isosorbide
Although NAC may enhance the effectiveness of nitroglycerin and isosorbide (two medications commonly used to treat chest pain), this combination may also increase the risk of side effects such as severe headaches and may lead to abnormally low blood pressure.

Oxiconazole
Topical applications of NAC may increase the effectiveness of oxiconazole, an antifungal medication used for athlete's foot.

Supporting Research
Adair JC, Knoefel JE, Morgan N. Controlled trial of N-acetylcysteine for patients with probable Alzheimer's disease. Neurology . 2001;57(8):1515-1517.
Ames BN. Micronutrient deficiencies: A major cause of DNA damage. Ann NY Acad Sci . 2000;889:87-106.
Andreassen OA, Dedeoglu A, Klivenyi P, Beal MF, Bush AI. N-acetyl-L-cysteine improves survival and preserves motor performance in an animal model of familial amylotrophic lateral sclerosis. Neuroreport . 2000;11(11):2491-2493.
Ardissino D, Merlini PA, Savonitto S, Demicheli G, et al. Effect of transdermal nitroglycerin or N-Acetylcysteine, or both, in the long-term treatment of unstable angina pectoris. J Am Coll Cardiol . 1997;29(5):941-947.
Arstall MA, Yang J, Stafford I, Betts WH, Horowitz JD. N-acetylcysteine in combination with nitroglycerin and streptokinase for treatment of evolving acute myocardial infarction: safety and biochemical effects. Circulation . 1995;92:2855-2862.
Behr J, Maier K, Degenkolb B, Krombach F, Vogelmeier C. Antioxidative and clinical effects of high-dose N-acetylcysteine in fibrosing alveolitis. Am J Respir Crit Care Med . 1997;156:1897-1901.
Beloqui O, Prieto J, Suarez M, et al. N-acetyl cysteine enhances the response to interferon-alpha in chronic hepatitis C: a pilot study. J Interferon Res . 1993;13:279-282.
Cai J, Nelson KC, Wu M, Sternberg P Jr, Jones DP. Oxidative damage and protection of the RPE. Prog Retin Eye Res . 2000;19(2):205-221.
Carter EA. Enhanced acetaminophen toxicity associated with prior alcohol consumption in mice; prevention by N-acetylcysteine. Alcohol . Jan-Feb 1987; 4(1): 69-71.
Chevez-Barrios P, Wiseman AL, Rojas E, Ou CN, Lieberman MW. Cataract develoment in gamma-glutamyl transpeptidase deficient mice. Exp Eye Res . 2000;71(6):575-582.
Chirkov YY, Horowitz JD. N-Acetylcysteine potentiates nitroglycerin-induced reversal of platelet aggregation. J Cardiovasc Pharmacol . 1996;28(3):375-380.
Christman BW, Bernard GR. Antilipid mediator and antioxidant therapy in adult respiratory distress syndrome. New Horiz . Nov 1993; 1(4): 623-630.
D'Agostini F, Bagnasco M, Giunciuglio D, Albini A, De Flora S. Inhibition by oral N-acetylcysteine of doxorubicin-induced clastogenicity and alopecia, and prevention of primary tumors and lung micrometastases in mice. Int J Oncol . 1998;13:217-224.
Davreux CJ, Soric I, Nathens AB, et al. N-acetylcysteine attenuates acute lung injury in the rat. Shock . Dec 1997; 8(6): 432-438.
De Flora S, D'Agostini F, Masiello L, Giunciuglio D, Albini A. Synergism between N-Acetylcysteine and doxorubicin in the prevention of tumorigenicity and metastasis in murine models. Int J Cancer. 1996;67:842-848.
De Rosa SC, Zaretsky MD, Dubs JG, Roederer M, Anderson M, Green A, et al. N-acetylcysteine replenishes glutathione in HIV infection. Eur J Clin Invest . 2000;30:915-929.
Domenighetti G, Quattropani C, Schaller MD. Therapeutic use of N-acetylcysteine in acute lung diseases. [Review, French]. Rev Mal Respir . 1999;16(1):29-37.
Domenighetti G, Suter PM, Schaller MD, Ritz R, Perret C. Treatment with N-acetylcysteine during acute respiratory distress syndrome: a randomized, double-blind, placebo-controlled clinical study. J Crit Care . 1997;12(4):177-182.
Doroshow JH, Locker GY, Ifrim I, Myers CE. Prevention of doxorubicin cardiac toxicity in the mouse by N-Acetylcysteine. J Clin Invest . 1981;68:1053-1064.
Droge W. Cysteine and glutathione deficiency in AIDS patients: a rationale for the treatment with N-acetyl-cysteine. [Review]. Pharmacology . 1993;46(2):61-65.
Franceschini G, et al. Dose-related increase in HDL-cholesterol levels after N-acetylcysteine in man. Pharmacol Res . Oct-Nov 1993; 28(3): 213-218.
Goodman MT, McDuffie K, Hernandez B, Wilkens LR, Selhub J. Case-control study of plasma folate, homocysteine, vitamin B12, and cysteine as markers of cervical dysplasia. Cancer . 2000;89:376-382.
Hershkovitz E, Shorer Z, Levitas A, Tal A. Status epilepticus following intravenous N-acetylcysteine therapy. Isr J Med Sci . 1996;32(11):1102-1104.
Iversen HK. N-acetylcysteine enhances nitroglycerin-induced headache and cranial artery response. Clin Pharmacol Ther . 1992;52:125-133.
Jackson IM, et al. Efficacy and tolerability of oral acetylcysteine (Fabrol) in chronic bronchitis: a double-blind placebo controlled study. J Int Med Res. 1984; 12(3): 198-206.
Kozer E, Koren G. Management of paracetamol overdose: current controversies. [Review]. Drug Saf . 2001;24(7):503-512.
Lenz AG, Jorens PG, Meyer B, et al. Oxidatively modified proteins in bronchoalveolar lavage fluid of patients with ARDS and patients at-risk for ARDS. Eur Respir J. 1999;13(1):169-174.
Marchetti G, Lodola E, Licciardello L, Colombo A. Use of N-acetylcysteine in the management of coronary artery diseases. Cardiologia . Jul 1999; 44(7): 633-637.
Micke P, Beeh KM, Schlaak JF, Buhl R. Oral supplementation with whey proteins increases plasma glutathione levels of HIV-infected patients. Eur J Clin Invest . 2001;31(2):171-178..
Muller F, Svardal AM, Nordoy I, Berge RK, Aukrust P, Froland SS. Virological and immunological effects of antioxidant treatment in patients with HIV infection. Eur J Clin Invest . 2000;30(10):905-914.
Patrick L. Hepatitis C: epidemiology and review of complementary/alternative medicine treatments. Alt Med Rev . 1999;4(4):220-238.
Pelle E, et al. Protection against cigarette smoke-induced damage to intact transformed rabbit corneal cells by N-acetyl-L-cysteine. Cell Biol Toxicol . Aug 1998; 14(4): 253-259.
Perry HE, Shannon MW. Efficacy of oral versus intravenous N-acetylcysteine in acetaminophen ovedose:results of an open-label, clinical trial. J Pediatr . Jan 1998;132(1): 149-152.
Pizzorno JE, Murray MT. Textbook of Natural Medicine . Vol 1. 2nd ed. Edinburgh: Churchill Livingstone; 1999:296-297.
Pizzulli, L, Hagendorff A, Zirbes M, Jung W, Lüderitz B. N-Acetylcysteine attenuates nitroglycerin tolerance in patients with angina pectoris and normal left ventricular function. Am J Cardiol . 1997;79:28-33.
Ruiz FJ, et al. N-acetyl-L-cysteine potentiates depressor response to captopril and enalaprilat in SHRs. Am J Physiol . Sep 1994; 267 (3 Pt 2): R767-772.
Shabert JK, Winslow C, Lacey JM, Wilmore DW. Glutamine antioxidant supplementation increases body cell mass in AIDS patients with weight loss: a randomized, double-blind controlled trial. Nutrition . 1999;11:860-864.
Shils, ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease . 9th ed. Baltimore, MD: Williams & Wilkins; 1999:543-556.
Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985). N Engl J Med . Dec 15 1988; 319(24): 1557-1562.
Stavem K. Anaphylactic reaction to N-acetylcysteine after poisoning with paracetamol. Tidsskr Nor Laegeforen. May 30 1997; 117(14): 2038-2039.
Stey C, Steurer J, Bachmann S, Medici TC, Tramer MR. The effect of oral N-acetylcysteine in chronic bronchitis: a quantitative systematic review. Eur Respir J . 2000 Aug;16(2):253-262.
Suárez C, Del Arco C, Lahera V, Ruilope LM. N-Acetylcysteine potentiates the antihypertensive effect of angiotensin converting enzyme inhibitors [letter]. Am J Hypertens . 1995;8:859-861.
van Hoogdalem EJ, van den Hoven WE, Terpstra IJ, van Zijtveld J, Verschoor, JSC. Nail penetration of the antifungal agent oxiconazole after repeated topical application in healthy volunteers, and the effect of acetylcysteine. Eur J Pharm Sci . 1997;5:119-127.
van Zandwijk N. N-acetylcysteine for lung cancer prevention. Chest . 1995;107(5):1437-1441.
Walters MT, et al. A double-blind, cross-over, study of oral N-acetylcysteine in Sjogren's syndrome. Scand J Rheumatol Suppl . 1986; 61: 253-258.

 

Review Date: 4/1/2002

Reviewed By: Participants in the review process include: Jacqueline A. Hart, MD, Department of Internal Medicine, Newton-Wellesley Hospital, Harvard University and Senior Medical Editor Integrative Medicine, Boston, MA; Gary Kracoff, RPh (Pediatric Dosing section February 2001), Johnson Drugs, Natick, Ma; Steven Ottariono, RPh (Pediatric Dosing section February 2001), Veteran's Administrative Hospital, Londonderry, NH; Margie Ullmann-Weil, MS, RD, specializing in combination of complementary and traditional nutritional therapy, Boston, MA. All interaction sections have also been reviewed by a team of experts including Joseph Lamb, MD (July 2000), The Integrative Medicine Works, Alexandria, VA;Enrico Liva, ND, RPh (August 2000), Vital Nutrients, Middletown, CT; Brian T Sanderoff, PD, BS in Pharmacy (March 2000), Clinical Assistant Professor, University of Maryland School of Pharmacy; President, Your Prescription for Health, Owings Mills, MD; Ira Zunin, MD, MPH, MBA (July 2000), President and Chairman, Hawaii State Consortium for Integrative Medicine, Honolulu, HI.



Quercetin:

University of Maryland Medical Center

Overview
Quercetin belongs to a group of plant pigments called flavonoids that are largely responsible for the colors of many fruits, flowers, and vegetables. Flavonoids, such as quercetin, provide many health-promoting benefits. They act as antihistamines (which are useful in reducing allergy symptoms) and help reduce inflammation associated with various forms of arthritis. Quercetin also works as an antioxidant by scavenging damaging particles in the body known as free radicals. These particles occur naturally in the body but can damage cell membranes, interact with genetic material, and possibly contribute to the aging process as well as the development of a number of conditions including heart disease and cancer. Antioxidants such as quercetin can neutralize free radicals and may reduce or even help prevent some of the damage they cause.

Uses
Quercetin offers a variety of potential therapeutic uses, primarily in the prevention and treatment of the conditions listed below. Of note is that quercetin seems to work better when used in conjunction with bromelain, a digestive enzyme found in pineapples, particularly for allergies and inflammation.

ALLERGIES, ASTHMA, HAYFEVER AND HIVES
Quercetin inhibits the production and release of histamine and other allergic/inflammatory substances. Histamine is a substance that contributes to allergy symptoms such as a runny nose, watery eyes, hives, and swelling of soft tissue including the face and lips.

HEART DISEASE
Test tube, animal, and some population-based studies suggest that the flavonoids quercetin, resveratrol, and catechins (all found in high concentration in red wine) may help reduce the risk of atherosclerosis (plaque buildup in the arteries that can lead to heart attack or stroke). By acting as antioxidants, these nutrients appear to protect against the damage caused by LDL ("bad") cholesterol and may help prevent death from heart disease. Additional rigorous studies in people are needed to confirm these findings.

HIGH CHOLESTEROL
Flavonoids, like quercetin, from red wine or orange juice may help lower cholesterol levels.

In a study of 3,072 adults with symptoms of macular degeneration, moderate red wine consumption (a source of quercetin) offered some protection against the development and progression of the disease. Dark berries, such as blueberries, blackberries, and dark cherries, are also high in flavonoids. Some suggest that eating these fruits regularly may also offer benefit for preventing macular degeneration.

Similarly, animal studies suggest that quercetin inhibits the activity of compounds that contribute to the development of cataracts.

ARTHRITIS
According to laboratory and animal studies, quercetin has anti-inflammatory properties. In test tubes, for example, quercetin inhibits the type of inflammation that can occur in the joints of those with arthritis. In addition, there are reports of people with rheumatoid arthritis who experienced an improvement in their symptoms when they switched from a typical Western diet to a vegan diet with lots of uncooked berries, fruits, vegetables, nuts, roots, seeds, and sprouts containing, amongst other antioxidants, quercetin.

FIBROMYALGIA
Similar to the case reports for arthritis, people with fibromyalgia who switched from a typical Western diet to a vegan diet high in flavonoids such as quercetin experienced improvement in their symptoms.

PROSTATE HEALTH
Some studies suggest that quercetin improves pain and other symptoms in men with chronic prostatitis (inflammation of the prostate). In addition, preliminary laboratory studies indicate that quercetin may inhibit the growth of prostate cancer cells in test tubes. How this will ultimately translate to prevention or treatment of prostate cancer in men is unknown at this time.

CANCER
Quercetin and other flavonoids from fruits and vegetables have long been considered important substances to possibly help prevent cancer. New laboratory studies are suggesting that this belief may be accurate. Quercetin and other flavonoids have been shown in animal and test tube studies to inhibit the growth of cancer cells, including those from breast, colon, prostate, and lung tumors.

One study evaluating quercetin in humans included 11 people with various forms of cancer. This study found that quercetin reduced the actual tumor size in two people and inhibited the activity of a protein that plays a role in tumor growth in nine of the 11 people. More studies are needed to further explore the possible beneficial effects of quercetin in people.

Researchers are also hopeful that quercetin and other flavonoids may prove to enhance the action of anti-cancer drugs. This issue, however, of using anti-oxidants at the same time as chemotherapy or radiation to treat cancer is controversial. Until more is known, it should likely be avoided.

CANKER SORES
Quercetin may reduce the frequency of mouth sores and produce mild symptomatic relief.

OTHER
Researchers have been evaluating medicinal plants in the Democratic Republic of Congo that have been used traditionally to treat diarrhea and dysentery. What they have found is that flavonoids, such as quercetin, are among the active ingredients in these plants. Studies in Russia regarding the use of quercetin, along with other supplements and/or conventional medications, to treat dysentery caused by infections such as Shigella have shown some promise.

Dietary Sources
Fruits and vegetables -- particularly citrus fruits, apples, onions, parsley, tea, and red wine -- are the primary dietary sources of quercetin. Olive oil, grapes, dark cherries, and dark berries, such as blueberries, blackberries, and bilberries are also high in flavonoids including quercetin.

Available Forms
Quercetin supplements are available in several strengths in powder or capsule form. They are often packaged with bromelain (an enzyme found in pineapple) as an anti-inflammatory agent. Bromelain exerts anti-inflammatory and anti-allergy activity of its own and also increases the absorption of quercetin. Other flavonoid-rich extracts include those from grape seed, bilberry, Ginkgo biloba, and green tea.

Precautions
No adverse effects from the use of quercetin have been reported. However, because supplements may have side effects or interact with medications, they should be taken only under the supervision of a knowledgeable healthcare provider.

Possible Interactions
If you are currently being treated with any of the following medications, you should not use quercetin supplements without first talking to your healthcare provider.

CHEMOTHERAPY
Test tube and animal studies suggest that quercetin may enhance the effects of doxorubicin and cisplatin, two chemotherapy medications used to treat cancer. More research is needed to determine if quercetin has any application to people being treated with either of these agents. In addition, use of antioxidants at the same time as chemotherapy is somewhat controversial. Therefore, more research is needed before conclusions about safety and effectiveness can be drawn.

Supporting Research
Cai J, Nelson KC, Wu M, Sternberg P Jr, Jones DP. Oxidative damage and protection of the RPE. Prog Retin Eye Res. 2000;19(2):205-221.
Chan MM, Mattiacci JA, Hwang HS, Shah A, Fong D. Synergy between ethanol and grape polyphenols, quercetin, and resveratrol, in the inhibition of the inducible nitric oxide synthase pathway. Bio Pharm. 2000;60(10):1539-1548.
Constant J. Alcohol, ischemic heart disease, and the French paradox. Clin Card. 1997;20(5):420-424.
Duthie SJ, Collins AR, Duthie GG, Dobson VL. Quercetin and myricetin protect against hydrogen peroxide-induced DNA damage (strand breaks and oxidised pyrimidines) in human lymphocytes. Mutat Res. 1997;393(3):223-231.
Ferry DR, Smith A, Malkhandi J, et al. Phase I clinical trial of the flavonoid quercetin pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. Clin Cancer Res. 1996;2(4):659-668.
Gross M, Pfeiffer M, Martini M, Campbell D, Slavin J, Potter J. The quantitation of metabolites of quercetin flavonols in human urine. Cancer Epidemiol Biomarkers Prevent. 1996;5(9):711-720.
Guardia T, Rotelli AE, Juarez AO, Pelzer LE. Anti-inflammatory properties of plant flavonoids. Effects of rutin, quercetin, and hesperidin on adjuvant arthritis in rat. Farmaco. 2001;56(9):683-687.
Hanninen, Kaartinen K, Rauma AL, Nenonen M, Torronen R, Hakkinen AS, Adlercreutz H, Laakso J. Antioxidants in vegan diet and rheumatic disorders. Toxicology. 2000;155(1-3):45-53. Hayek T, Fuhrman B, Vaya J, Rosenblat M, Belinky P, Coleman R et al. Reduced progression of atherosclerosis in apolipoprotein E-deficient mice following consumption of red wine, or its polyphenols quercetin or catechin, is associated with reduced susceptibility of LDL to oxidation and aggregation. Arterioscler Thromb Vasc Biol. 1997;17(11):2744-2752.
Head KA. Natural therapies for ocular disorders. Part 1: diseases of the retina. Alt Med Rev. Oct. 1999;(4):5:342-359.
Hofmann J, Fiebig HH, Winterhalter BR, Berger DP, Grunicke H. Enhancement of the antiproliferative activity of cis-diamminedichloroplatinum (II) by quercetin. Int J Cancer. 1990;45(3):536-539.
Hollman PC, Van Trijp JM, Mengelers MJ, De Vries JH, Katan, MB. Bioavailability of the dietary antioxidant flavonol quercetin in man. Cancer Lett. 1997;114(1-2):139-140.
Knekt P, Isotupa S, Rissanen H, Heliovaara M, Jarvinen R, Hakkinen S et al. Quercetin intake and the incidence of cerebrovascular disease. Eur J Clin Nut. 2000;54(5):415-417.
Knekt P, Jarvinen R, Reunanen A, Maatela J. Flavonoid intake and coronary mortality in Finland: a cohort study. BMJ (Clinical Research Ed.). 1996;312(7029):478-481.
Kurowska EM, Spence JD, Jordan J, Wetmore S, Freeman DJ, Piche LA, Serratore P. HDL-cholesterol-raising effect of orange juice in subjects with hypercholesterolemia. Am J Clin Nutr. 2000;72(5):1095-1100.
Lamson DW, Brignall MS. Antioxidants and cancer III: quercetin. Alt Med Rev. 2000;5(3):196-208.
Lee E, Choi EJ, Cheong H, Kim YR, Ryu SY, Kim KM. Anti-allergic actions of the leaves of Castanea crenata and isolation of an active component responsible for the inhibition of mas cell degranulation. Arch Pharm Res. 1999;22(3):320-323.
Longanga OA, Vercruysse A, Foriers A. Contribution to the ethnobotanical, phytochemical and pharmacological studies of traditionally used medicinal plants in the treatment of dysentery and diarrhoea in Lomela area, Democratic Republic of Congo (DRC). J Ethnopharmacol. 2000;71(3):411-423.
Otshudi AL, Foriers A, Vercruysse A, Van Zeebroeck A, Lauwers S. In vitro antimicorbial activity of six medicinal plants traditionally used for the treatment of dysentery and diarrhoea in Democratic Republic of Congo (DRC). Phytomedicine. 2000;7(2):167-172.
Otsuka H, Inaba M, Fuikikura T, Kunitomo M. Histochemical and functional characteristics of metachromatic cells in the nasal epithelium in allergic rhinitis: studies of nasal scrapings and their dispersed cells. J Allergy Clin Immunol. 1995;96(4):528-536.
Owen RW, Giacosa A, Hull WE, Haubner R, Spiegelhalder B, Bartsch H. The antioxidant/anticancer potential of phenolic compounds isolated from olive oil. Eur J Cancer. 2000a;36(10):1235-1247.
Owen RW, Mier W, Giacosa A, Hull WE, Spiegelhalder B, Bartsch H. Identification of lignans as major components in the phenolic fraction of olive oil. Clin Chem. 2000b;46(7):976-988.
Piantelli M, Maggiano N, Ricci R, et al. Tamoxifen and quercetin interact with type II estrogen binding sites and inhibit the growth of human melanoma cells. J Invest Dermatol. 1995;105(2):248-53.
Rodgers EH, Grant MH. The effect of the flavonoids, quercetin, myricetin, and epicatechin on the growth and enzyme activities of MCF7 human breast cancer cells. Chem Bio Interactions. 1998;116(3):213-228.
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TAURINE:

PDRhealth.com’s research summary for the effects of taurine:

In a study of 24 subjects with congestive heart failure, administration of 2 grams of taurine, twice a day, resulted in clinical improvement in 19 patients. Roentgenographic data helped confirm the improvement. These positive results were subsequently confirmed in a double-blind, randomized, crossover, placebo-controlled study in which taurine was added to conventional treatment for a four-week period. Compared with placebo, taurine produced significant improvement as evaluated by a number of measures, including chest films. In still another study, supplemental taurine, but not coenzyme Q10, was said to have significant benefit in patients with congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. This was a double-blind study using 3 grams of taurine daily.

Taurine has demonstrated hypotensive effects in some animal studies. In humans, it has lowered blood pressure in borderline hypertensive patients using 6 grams of taurine daily for seven days. Lipid-lowering effects have been seen in animals, but human data are few and contradictory. There is some preliminary evidence from one small study that 0.4 to 1.6 grams of taurine daily for eight days inhibited platelet aggregation in a dose-dependent manner.

Supplementation with 1.5 grams of taurine daily decreased platelet aggregation in subjects with type 1 diabetes. Insulin sensitivity was significantly improved by taurine supplementation in a rat model of spontaneous type 2 diabetes. Serum cholesterol and triacylglycerol were decreased in the supplemented animals. Taurine was also effective in another animal model of insulin resistance.

Taurine has exerted some detoxifying effects in animal experiments. It helped prevent bleomycin-induced lung injury and fibrosis in mice. It also appeared to have protective effects, as measured by changes in memory and lipid peroxidation levels in the brain, in rats exposed to ozone. Additionally, it has inhibited ethanol-induced elevation of plasma acetaldehyde in other animal studies. In one of these, it prevented the development of ethanol-induced hypertension in rats.

In some older studies, taurine demonstrated some preliminary ability to suppress some epileptic seizures. Follow-up is needed.

Finally, taurine was shown to be of benefit in a study of 22 Canadian children with cystic fibrosis and documented steatorrhea. They were given taurine (30 mg/kg/day) and placebo during separate six-month periods. Severity of fat malabsorption was significantly reduced in most of the subjects, especially in those with the most severe steatorrhea. A more recent study, however, failed to note these benefits, but significant differences in the two study groups may account for this discrepancy. A second study by the Canadian group showed positive effects of taurine on fat absorption in cystic fibrosis patients. Again, those with the greatest malabsorption at baseline seemed to benefit the most.

Journal Citations:


Progress in research on function and mechanism of cardiac vascular system of taurine
Author:                       Hua,-H-M; Ito,-T; Qiu,-Z-G; Azuma,-J
Citation:         Zhongguo-Zhong-Yao-Za-Zhi. 2005 May; 30(9): 653-8
Abstract:        The function for cardiac vascular system of taurine is extensive, and the mechanism is complicated. Taurine protects the cells from the cell injury caused by ischemia etc. Through repressing apoptosis, prevents endothelial dysfunction caused by hyperglycemia, hypercholesterolemia, smoking and homocysteine; suppresses the proliferation and calcification in vascular smooth muscle cells, promotes metabolization and excretion of cholesterol in the animal models of hyperlipemia, and confers the resistance to an oxidant, hypochlorous acid, produced by neutrophil on cells, and taurine chrolamine to inhibit activation of NF-kappaB, which might be associated with anti-atherosclerotic effect. Taurine mainly acts inside the cell. However, taurine transport system becomes aberrant in pathological myocardial and vascular tissue. In addition, taurine improves cardiovascular function in fructose-induced hypertension and an iron-overload murine animal models.


Taurine protected myocardial mitochondria injury induced by hyperhomocysteinemia in rats.
Author:                       Chang,-L; Xu,-J; Yu,-F; Zhao,-J; Tang,-X; Tang,-C
Citation:         Amino-Acids. 2004 Aug; 27(1): 37-48
Abstract:        Taurine can protect against cardiovascular diseases, whereas elevated levels of plasma homocysteine are associated with atherosclerotic and thromboembolic cardiovascular diseases. To illustrate the effects of taurine on hyperhomocysteinemia, we observed the myocardial mitochondria dysfunction in the rats with hyperhomocysteinemia induced by diet methionine loading, and the therapeutic effect of taurine. A methionine diet increased plasma homocysteine concentration (133.51 +/- 27.91 micromol/L vs 12.31 +/- 2.58 micromol/L in control, P < 0.01), stimulated the production of reactive oxygen species (ROS) in the myocardial mitochondria, and inhibited the activities of mitochondrial Mn-superoxide dismutase and catalase. The 45Ca uptake and Ca2+-ATPase activity in the myocardial mitochondria were significantly lowered in rats with hyperhomocysteinemia. Taurine supplements effectively attenuated the hyperhomocysteinemia-induced ROS production and inhibition of Mn-superoxide dismutase and catalase activities in the myocardial mitochondria, and increased its 45Ca uptake and Ca2+-ATPase activity. Thus, taurine antagonizes the oxidative stress injury in the myocardial mitochondria induced by the hyperhomocysteinemia.

Taurine supplementation reduces oxidative stress and improves cardiovascular function in an iron-overload murine model.
Author:                       Oudit,-G-Y; Trivieri,-M-G; Khaper,-N; Husain,-T; Wilson,-G-J; Liu,-P; Sole,-M-J; Backx,-P-H
Citation:         Circulation. 2004 Apr 20; 109(15): 1877-85
Abstract:        BACKGROUND: Iron overload has an increasing worldwide prevalence and is associated with significant cardiovascular morbidity and mortality. Elevated iron levels in the myocardium lead to impaired systolic and diastolic function and elevated oxidative stress. Taurine accounts for 25% to 50% of the amino acid pool in myocardium, possesses antioxidant properties, and can inhibit L-type Ca2+ channels. Thus, we hypothesized that this agent would reduce the cardiovascular effects of iron overload. METHODS AND RESULTS: Iron-overloaded mice were generated by intraperitoneal injection of iron either chronically (5 days per week for 13 weeks) or subacutely (5 days per week for 4 weeks). Iron overload causes increased mortality, elevated oxidative stress, systolic and diastolic dysfunction, hypotension, and bradycardia. Taurine supplementation increased myocardial taurine levels by 45% and led to reductions in mortality and improved cardiac function, heart rate, and blood pressure in iron-overloaded mice. Histological e xamination of the myocardium revealed reduced apoptosis and interstitial fibrosis in iron-overloaded mice supplemented with taurine. Taurine mediated reduced oxidative stress in iron-overloaded mice along with attenuation of myocardial lipid peroxidation and protection of reduced glutathione level. CONCLUSIONS: These results demonstrate that treatment with taurine reduces iron-mediated myocardial oxidative stress, preserves cardiovascular function, and improves survival in iron-overloaded mice. The role of taurine in protecting reduced glutathione levels provides an important mechanism by which oxidative stress-induced myocardial damage can be curtailed. Taurine, as a dietary supplement, represents a potential new therapeutic agent to reduce the cardiovascular burden from iron-overload conditions.

Taurine and vitamin C modify monocyte and endothelial dysfunction in young smokers.
Author:                       FM Fennessy, DS Moneley, JH Wang, CJ Kelly, and DJ Bouchier-Hayes.
Citation:         Circulation (Circulation) 2003 107:410-415.
Abstract:        BACKGROUND: Endothelial dysfunction initiated by monocyte-endothelial interactions has previously been observed in many vasculopathies, including chronic cigarette smoking. Taurine, a semiessential amino acid, and vitamin C, a naturally occurring antioxidant, have previously been shown to have endothelial protective effects when exposed to proinflammatory insults. Therefore, we hypothesized that taurine and vitamin C would restore endothelial function in young smokers by modifying monocyte-endothelial interactions. METHODS AND RESULTS: Endothelial-dependent vasodilatation was assessed in vivo using duplex ultrasonography, and monocyte-endothelial interactions were assessed in vitro using endothelial cell culture (human umbilical vein endothelial cells [HUVECs]) with monocyte-conditioned medium (MCM). Endothelial-dependent vasodilatation was significantly impaired in young smokers compared with nonsmokers. Pretreatment of young smokers for 5 days with 2 g/d vitamin C and, more significantly, with 1.5 g/d taurine attenuated this response. MCM taken from smokers impaired the release of nitric oxide and increased the levels of endothelin-1 release from HUVECs. When HUVECs were cultured with MCM from smokers who had been treated with taurine, the levels of nitric oxide and endothelin-1 returned toward control levels. This was attributed to an upregulation in endothelial nitric oxide synthase expression. CONCLUSIONS: These observations suggest that taurine supplementation has a beneficial impact on macrovascular endothelial function, and an investigation of its effect on altered endothelial function in dyslipidemic states is warranted.

Supplementary taurine may stabilize atheromatous plaque by antagonizing the activation of metalloproteinases by hypochlorous acid.
Author:                       McCarty,-M-F
Citation:         Med-Hypotheses. 2004; 63(3): 414-8
Abstract:        The rupture of atherosclerotic plaque, responsible for triggering the majority of myocardial infarctions, presumably requires proteolysis of collagen fibers and other protein components of the intercellular matrix. This is achieved by activated matrix metalloproteases (MMPs) secreted by intimal macrophages and foam cells. MMPs are synthesized as inactive pro-enzymes in which coordinate binding of the thiol group of a key cysteine residue to the active-site zinc atom blocks proteolytic activity. Physiological activation of MMPs is mediated, in large measure, by phagocyte-derived hypochlorous acid (HOCL), which can oxidize the zinc-bound thiol to sulfinic acid, thus freeing the active-site zinc. HOCL also encourages proteolysis of ground substance by inactivating proteins such as TIMP-1 that are physiological inhibitors of MMPs. In vivo, the unrestrained oxidant activity of HOCL is opposed by taurine, which reacts spontaneously with HOCL to generate taurine chloramine, much more stable than HOCL. Taurine chloramine has less impact than HOCL on MMP activation, and does not impair the activity of TIMP-1. Since tissue levels of taurine can be boosted via supplementation, taurine may thus have potential for stabilizing plaque and thereby warding off infarction--an effect that should be reinforced by taurine's platelet-stabilizing activity. In light of recent epidemiological evidence that increased expression of myeloperoxidase - the enzyme which generates HOCL--is an important risk factor for coronary disease, supplemental taurine may indeed have broader utility for suppressing both the genesis and the rupture of atherosclerotic plaque. Copyright 2004 Elsevier Ltd.

PREVENTION AND TREATMENT OF DIABETES:

Taurine supplementation and diabetes mellitus.
Author:                       Franconi,-F; Loizzo,-A; Ghirlanda,-G; Seghieri,-G
Citation:         Curr-Opin-Clin-Nutr-Metab-Care. 2006 Jan; 9(1): 32-6
Abstract:        PURPOSE OF REVIEW: Taurine is a semi-essential sulphur amino acid derived from methionine and cysteine metabolism. It has been evaluated either in experimental or clinical type 1 and 2 diabetes mellitus and insulin resistance. One form of experiment has included the possibility that perinatal taurine administration could prevent diabetes mellitus and/or insulin resistance. RECENT FINDINGS: Experimental data suggest strongly that taurine could have beneficial effects in type 1 diabetes mellitus, and could generally reduce organ lipid peroxidation and plasma lipids. Interestingly, retina, lens and nerves seem to respond better to taurine than other organs such as kidneys. It has been shown in some experimental models that in type 2 diabetes mellitus and insulin resistance there is alteration in taurine homeostasis. Taurine could prevent the onset of diabetes mellitus in NOD mice and postnatal taurine modifies the glucose-loading curves in adults. However, the clinical studies are too small and too short to have any real significance. SUMMARY: Further experimental and clinical studies are required to evaluate taurine's possible therapeutic potential. Careful attention has to be paid in the selection of animal species, in standardization of taurine concentrations and patient selection. Moreover, care must also be given to the metabolic state, presence of complications, duration of supplementations and selection of the right end-points.

Taurine prevents collagen abnormalities in high fructose-fed rats.
Author:                       Nandhini,-A-T; Thirunavukkarasu,-V; Anuradha,-C-V
Citation:         Indian-J-Med-Res. 2005 Aug; 122(2): 171-7
Abstract:        BACKGROUND & OBJECTIVE: Accumulation of collagen and changes in its physiochemical properties contribute to the development of secondary complications of diabetes. We undertook this study to see the effects of taurine on the content and characteristics of collagen from tail tendon of rats fed with high fructose diet. METHODS: The rats were divided into four groups of six each: control group (CON), taurine-supplemented control group (CON+TAU), taurine supplemented (FRU+TAU) and not supplemented fructose-fed group (FRU). The physico-chemical properties of collagen isolated from the tail tendon were studied. RESULTS: Fructose administration caused accumulation of collagen in tail tendon. Enhanced glycation and advanced glycation end products (AGE)-linked fluorescence together with alterations in aldehyde content, solubility pattern, susceptibility to denaturing agents and shrinkage temperature were observed in fructose-fed rats. Elevated b component of type I collagen was evidenced from the SDS gel pattern of collagen from the fructose-fed rats. Simultaneous administration of taurine alleviated these changes. INTERPRETATION & CONCLUSION: Taurine administration to fructose-rats had a positive influence on both quantitative and qualitative properties of collagen. The results of the present study suggested a role for the action of taurine in delaying diabetic complications and the possible use of taurine as an adjuvant therapeutic measure in the management of diabetes and its complications.

Taurine supplement in early life altered islet morphology, decreased insulitis and delayed the onset of diabetes in non-obese diabetic mice.
Author:                       Arany,-E; Strutt,-B; Romanus,-P; Remacle,-C; Reusens,-B; Hill,-D-J
Citation:         Diabetologia. 2004 Oct; 47(10): 1831-7
Abstract:        AIMS/HYPOTHESIS: We hypothesised that nutritional taurine, which is important for the development of the endocrine pancreas and reduces cytokine-induced apoptosis in pancreatic beta cells, would prevent or delay the onset of autoimmune diabetes, if given early in life to the non-obese diabetic (NOD) mouse. METHODS: Pregnant NOD mice received a diet supplemented with taurine throughout gestation or until weaning, and the pancreas of the offspring was examined using immunohistochemistry. This was done at postnatal day 14 and after 8 weeks (assessment of insulitis). The animals were also monitored until they became diabetic. RESULTS: At 14 days, pancreatic islet mass was significantly greater in animals treated with taurine than in controls. This finding was associated with a greater incidence of islet cell proliferation and a lower incidence of apoptosis. At age 8 weeks the number of islets manifesting insulitis was reduced by more than half, and the area of insulitis was reduced by 90%. Taurine treatment delay ed the mean onset time of diabetes from 18 to 30 weeks in females, and from 30 to 38 weeks in males, while 20% of treated females remained free of diabetes after one year. CONCLUSIONS/INTERPRETATION: Taurine supplementation in early life altered islet development, reduced insulitis and delayed the onset of diabetes in NOD mice.

Stimulation of glucose utilization and inhibition of protein glycation and AGE products by taurine.
Author:                       Nandhini,-A-T; Thirunavukkarasu,-V; Anuradha,-C-V
Citation:         Acta-Physiol-Scand. 2004 Jul; 181(3): 297-303
Abstract:        AIM: Pathological effects of the process of non-enzymatic glycation of proteins are reflected in chronic complications of diabetes mellitus. We investigated the antiglycating effect of taurine in high fructose fed rats in vivo and the inhibiting potency of taurine in the process of in vitro glycation. Additionally, we investigated whether taurine enhances glucose utilization in the rat diaphragm. METHODS: Rats fed a high fructose diet (60% total calories) were provided 2% taurine solution for 30 days. The effects of taurine on plasma glucose, fructosamine, protein glycation and glycosylated haemoglobin in high fructose rats were determined. For in vitro glycation a mixture of 25 mm glucose and 25 mm fructose was used as glycating agent, bovine serum albumin as the model protein and taurine as the inhibitor. Incubations were carried out in a constant temperature bath at 37 degrees C for 3-30 days. Amadori products and advanced glycation end products (AGEs) formed were measured. In vitro utilization of glucose was carried out in the rat diaphragm in the presence and absence of insulin in which taurine was used as an additive. RESULTS: The contents of glucose, glycated protein, glycosylated haemoglobin and fructosamine were significantly lowered by taurine treatment to high fructose rats. Taurine prevented in vitro glycation and the accumulation of AGEs. Furthermore, taurine enhanced glucose utilization in the rat diaphragm. This effect was additive to that of insulin and did not interfere with the action of insulin. CONCLUSIONS: These results underline the potential use of taurine as a therapeutic supplement for the prevention of diabetic pathology.

Long-term taurine supplementation reduces mortality rate in streptozotocin-induced diabetic rats.
Author:                       Di-Leo,-M-A; Santini,-S-A; Gentiloni-Silveri,-N; Giardina,-B; Franconi,-F; Ghirlanda,-G
Citation:         Amino-Acids. 2004 Oct; 27(2): 187-91
Abstract:        Oxidative stress is implicated in the pathogenesis of diabetes mellitus. Taurine and vitamin E+selenium supplementation has some benefits in experimental models of diabetes mellitus. This study evaluates whether taurine and vitamin E+selenium supplementations reduce a hard end-point such as mortality due to diabetes. Streptozotocin-induced diabetic rats were fed with standard diet or taurine (5%, w/w) or vitamin E (500 UI/Kg)+selenium (8 mg/ Kg) enriched diets. Taurine significantly decreased mortality rate (p < 0.04), while vitamin E failed to increase survival. In the late phase of the disease, taurine significantly decreased glycaemia, being vitamin E ineffective. No correlation between glycaemia and survival was found. None of supplementations modified body weight. Thus, only taurine decreases the mortality rate and glycaemia. These results encourage new research in the field, since classical hypoglycaemic agents are unable to decrease mortality in diabetic patients.



GRAPE SEED EXTRACT:

Grape Seed Extract
WebMD:  Heady Over Grapes?
Can the seeds heal? By  Laura Lane WebMD Feature  
         
Sept. 11, 2000 -- At 42, Linda Walsh of Buena Park, Calif., could hardly believe that age spots were spreading up her shins and down her feet. To make matters worse, her hair was beginning to fall out, her joints were becoming stiffer by the day, and fatigue weighed every step she took.

Then she discovered grape-seed extract.

Now, four years later, Walsh's skin is free of blemishes, her hair is lustrous and full, and there's a new bounce in her stride. "I feel good and I look five years younger than before," she says. For this transformation, Walsh gives credit to an extract taken from the seeds of ordinary grapes. She's so enthusiastic that she now sells the extract and other supplements full time.

Indeed, glowing testimonials from people like Walsh have made grape-seed extract one of the most popular supplements in the United States. In 1999, Americans spent $141 million on grape-seed products, a jump of 26% over the previous year, according to The Hartman Group, a market research firm.

So do grape seeds really work? The question is far from settled, but scientists aren't ready to rule out the possibility that they might. The key ingredient in grape seeds has shown promise against disease-causing chemicals in test tubes. And a few preliminary experiments in humans have produced intriguing results.

Super-Antioxidant
One reason it's not easy to weigh the claims for grape-seed extract is that much of the research is done by people with a stake in selling it. Many of the studies most often cited come from the laboratory of Debasis Bagchi, PhD, a Creighton University professor of pharmaceutical and administrative sciences who also works for grape-seed product maker InterHealth Nutraceuticals.

Bagchi has labored to show that a substance within grape-seed extract, oligoproanthocyanidin, or OPC, is a powerful antioxidant. Antioxidants disarm free radicals -- molecules that can damage DNA, cells, and tissues, eventually contributing to heart disease, cancer, and other illnesses. Because of its structure, one OPC molecule can neutralize several free radicals at once, while each molecule of better-known antioxidants like vitamins C and E can handle only one at a time, Bagchi says.

Putting It to the Test
In one experiment, Bagchi and his team placed OPC, vitamin C, and vitamin E in three separate test tubes filled with free radicals similar to those found in the body. After 15 minutes, the researchers found that OPC had knocked out up to 81% of the free radicals in its test tube. By comparison, vitamin C and E neutralized up to 19% and 44%, respectively. (See the February 1997 issue of the journal Research Communications in Molecular Pathology and Pharmacology.)

While such findings are promising, they don't prove that grape-seed extract can actually prevent or cure heart disease, cancer, or any other illness, says Harry Preuss, MD, of Georgetown University, who led the cholesterol study (which was partly funded by InterHealth Nutraceuticals). "The benefits are potentially there," he says. But in order to know how a human being's health is really affected over a long period of time, "You have to do these huge, huge studies." So far, no one has been willing to pay the cost of such a study.

Patching the Pipes
Nor has anyone funded a conclusive study on the other intriguing claim made for grape-seed extract: that it reinforces collagen and elastin, the bricks and mortar of blood vessels and other supportive tissues.