WHAT IS IT?
Vitamin C, also known as ascorbic acid, is a water-soluble micro-nutrient. Human beings cannot manufacture their own vitamin C and must rely on outside sources, including food and supplements, to obtain it. Other forms of vitamin C, which may be found in supplements include, ascorbyl palmitate (a fat-soluble form) and mineral ascorbates such as calcium ascorbate.

Vitamin C is found in different fruits and vegetables. Although the vitamin C content varies depending upon the produce,¹ about five servings (2½ cups) of fruits and vegetables should average out to about 200 mg of vitamin C. Rich sources of vitamin C include sweet red peppers, strawberries, orange juice, grapefruit juice, oranges, and broccoli. Other good sources include grapefruit, tomatoes and potato.

WHAT DOES IT DO?
Vitamin C is best known for its role in the synthesis of collagen, a connective tissue protein used as a structural component of blood vessels, tendons, ligaments, and bone. A deficiency of vitamin C leads to the deficiency disease “scurvy,” characterized by insufficient collagen production. This water-soluble vitamin is also needed for the synthesis of: 1) the neurotransmitter norepinephrine, which performs critical brain function including an effect on mood, and 2) the amino acid carnitine, which is essential for the transport of fat into cellular mitochondria, where the fat is converted to energy or ATP.² Vitamin C may also be involved in the metabolism of cholesterol to bile acids, which may be important for blood cholesterol levels and the incidence of gallstones.³

Another significant function of vitamin C is the important role it plays as an antioxidant, protecting vital molecules in the body from damage by free radicals and reactive oxygen species. These molecules include proteins, lipids (fats), carbohydrates, and nucleic acids (DNA and RNA). Vitamin C also plays a complementary role with other antioxidants, such as vitamin E, helping to regenerate them from their oxidized form back into their reduced (active) form.^4,5

Vitamin C also plays a profound role in the health of the immune system, stimulating the production and function of white blood cells, including leukocytes, neutrophils, lymphocytes and phagocytes.^{6,7,8,9,10,11,12} In addition, research has demonstrated that supplemental vitamin C increases serum levels of antibodies^13,14 and C1q complement proteins.^15,16,17 Also, vitamin C has been shown to increase interferon levels in vitro,¹⁸ and research on supplemental vitamin C and the common cold suggests that it promotes an antiviral effect in humans.¹⁹

WHO SHOULD USE IT?
Given that humans do not make any vitamin C themselves, everyone would do well to supplement with vitamin C. This is especially true during times when additional immune support is desirable—such as during cold and flu season.

DOSAGE/TIMING
The RDA for vitamin C is 90 mg for men and 75 mg for women. The RDA for men and women smokers is 125 mg and 110 mg, respectively. However, studies conducted at the National Institutes of Health indicated that plasma and circulating cells in healthy subjects attain near-maximal concentrations of vitamin C at a dose of about 400 mg/day—a dose much higher than the current RDA.²⁰ This suggests that a daily intake of 400 mg is advisable.

Vitamin C can be taken with or without food, so the timing is not critical.

ADVERSE REACTIONS/ INTERACTIONS
An adult dose of up to 10 grams of vitamin C daily has not been found to be toxic or detrimental to health. High dose of vitamin C, however, may induce diarrhea. The concept of “bowel tolerance” describes utilizing vitamin C in amounts just short of the doses, which produce diarrhea.²¹ The Food and Nutrition Board recommends an upper limit of 2,000 mg daily in order to prevent most adults from experiencing diarrhea and gastrointestinal disturbances.²²

There is some controversial evidence that high doses of vitamin C (16 grams/day) reduced the response to warfarin in two people,^23,24 possibly by causing diarrhea and reducing warfarin absorption.²⁵ To be safe, individuals on anticoagulants should limit their vitamin C intake to 1 gram/day.

CONCLUSION
In conclusion, vitamin C performs several important roles in the body. It is necessary for the synthesis of the structural protein collagen, needed for blood vessels, tendons, ligaments, and bone, as well as for the synthesis of the neurotransmitter norepinephrine, which affects mood. Vitamin C is also necessary for the synthesis of the amino acid carnitine, which is essential for fat transport and energy production. This critical nutrient may be involved in the metabolism of cholesterol to bile acids and provides significant antioxidant protection against free radicals. Finally, vitamin C plays a profound role in the health of the immune system, stimulating the production and function of white blood cells.

Endnotes

1. U.S. Department of Agriculture, Agricultural Research Service. USDA National Nutrient Database for Standard Reference, Release 22. 2009. Available at: http://www.nal.usda.gov/fnic/foodcomp/search/.
2. Carr AC, Frei B. Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans. Am J Clin Nutr. 1999;69(6):1086–107.
3. Simon JA, Hudes ES. Serum ascorbic acid and gallbladder disease prevalence among US adults: the Third National Health and Nutrition Examination Survey (NHANES III). Arch Intern Med. 2000;160(7):931–6.
4. See note 2 above.
5. Bruno RS, Leonard SW, Atkinson J, et al. Faster plasma vitamin E disappearance in smokers is normalized by vitamin C supplementation. Free Radic Biol Med. 2006;40(4):689–97.
6. Prinz W, Bortz R, Bregin B, Hersch M. The effect of ascorbic acid supplementation on some parameters of the human immunological defense system. Int J Vitam Nutr Res. 1977;47(3):248–57.
7. Vallance S. Relationships between ascorbic acid and serum proteins of the immune system. Br Med J. 1977;2(6084):437–438.
8. Kennes B, Dumont I, Brohee D, Hubert C, Neve P. Effect of vitamin C supplements on cell-mediated immunity in old people. Gerontology. 1983;29(5):305–10.
9. Panush RS, Delafuente JC, Katz P, Johnson J. Modulation of certain immunologic responses by vitamin C. III. Potentiation of in vitro and in vivo lymphocyte responses. Int J Vitam Nutr Res Suppl. 1982;23:35–47.
10. Jariwalla RJ, Harakeh S. Antiviral and immunomodulatory activities of ascorbic acid. In: Harris JR (ed). Subcellular Biochemistry. Vol. 25. Ascorbic Acid: Biochemistry and Biomedical Cell Biology. New York: Plenum Press; 1996:215–31.
11. Levy R, Shriker O, Porath A, Riesenberg K, Schlaeffer F. Vitamin C for the treatment of recurrent furunculosis in patients with impaired neutrophil functions. J Infect Dis. 1996;173(6):1502–5.
12. Anderson R, Oosthuizen R, Maritz R, Theron A, Van Rensburg AJ. The effects of increasing weekly doses of ascorbate on certain cellular and humoral immune functions in normal volunteers. Am J Clin Nutr. 1980;33(1):71–6.
13. Prinz W, Bloch J, Gilich G, Mitchell G. A systematic study of the effect of vitamin C supplementation on the humoral immune response in ascorbate-dependent mammals. I. The antibody response to sheep red blood cells (a T-dependent antigen) in guinea pigs. Int J Vitam Nutr Res. 1980;50(3):294–300.
14. Feigen GA, Smith BH, Dix CE, et al. Enhancement of antibody production and protection against systemic anaphylaxis by large doses of vitamin C. Res Commun Chem Pathol Pharmacol. 1982;38(2):313–33.
15. Haskell BE, Johnston CS. Complement component C1q activity and ascorbic acid nutriture in guinea pigs. Am J Clin Nutr. 1991;54(6 Suppl):1228S–30S.
16. Johnston CS, Cartee GD, Haskell BE. Effect of ascorbic acid nutriture on protein-bound hydroxyproline in guinea pig plasma. J Nutr. 1985;115(8):1089–93.
17. Johnston CS, Kolb WP, Haskell BE. The effect of vitamin C nutriture on complement component C1q concentrations in guinea pig plasma. J Nutr. 1987;117(4):764–8.
18. Dahl H, Degre M. The effect of ascorbic acid on production of human interferon and the antiviral activity in vitro. Acta Pathol Microbiol Scand B. 1976;84B(5):280–4.
19. Sasazuki S, Sasaki S, Tsubono Y, Okubo S, Hayashi M, Tsugane S. Effect of vitamin C on common cold: randomized controlled trial. Eur J Clin Nutr. 2006;60(1):9–17.
20. Higdon J, Drake VJ. Vitamin C. Linus Pauling Institute, Oregon State University. 2006-2009. Retrieved June 15, 2011 from http://lpi.oregonstate.edu/infocenter/vitamins/vitaminC/index.html#lpi_recommend.
21. Cathcart RF. Vitamin C, titrating to bowel tolerance, anascorbemia, and acute induced scurvy. Med Hypotheses. 1981;7(11):1359–76.
22. Food and Nutrition Board, Institute of Medicine. Vitamin C. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington D.C.: National Academy Press; 2000:95–185.
23. Rosenthal G. Interaction of ascorbic acid and warfarin. JAMA 1971;215:1671.
24. Smith EC, Skalski RJ, Johnson GC, Rossi GV. Interaction of ascorbic acid and warfarin. JAMA 1972;221:1166.
25. Feetam CL, Leach RH, Meynell MJ. Lack of a clinically important interaction between warfarin and ascorbic acid. Toxicol Appl Pharmacol 1975;31:544–7.

The post An Overview Of Vitamin C appeared first on Total Health Magazine.

Resveratrol Background
Before jumping into a discussion about the fascinating human research, however, let’s take a moment to review just what resveratrol is, in case you’re unfamiliar with it. Resveratrol is a type of natural phenol by several plants in response to injury or attack by pathogens.^3,4 These plants include grapes, peanuts⁵ and Japanese Knotweed (Polygonum cuspidatum).⁶ Resveratrol helps provide protection to the plants, at least in part, due to its demonstrated antioxidant properties.⁷ These antioxidant properties benefit humans too, as shown in research where resveratrol provided a direct antioxidant effect against free radicals, and facilitated an increase in vitamin E⁸—another powerful antioxidant.

There are two primary isomers (i.e. two forms) of resveratrol, trans- and cis-. To be clear, trans-resveratrol has been unequivocally shown to have much greater activity than cis-resveratrol.⁹ Consequently, when purchasing a resveratrol product, make sure to check the supplement facts panel to verify that the product contains trans-resveratrol. If just”resveratrol” is listed, without the trans-designation, or if cis-resveratrol is listed, you would be better off choosing a different product that lists trans-resveratrol. In any case, for ease of reading, I will drop references to trans– in the rest of this article, although it can be assumed that any mention of resveratrol will actually refer to trans-resveratrol.

Cardiovascular Health
As its first claim to fame, resveratrol has been found to have activity that may have protective effects on the cardiovascular system. In both test-tube and animal research, resveratrol has been shown to inhibit platelet aggregation (i.e. the clumping together of blood platelets). This has value since excessive or inappropriate aggregation of platelets can lead to formation of blood clots and subsequent blockages in blood vessels that result in insufficient blood flow, heart attack or stroke.¹⁰ Resveratrol can also promote vasodilation (a relaxed and expanded state of the artery that accommodates increased blood flow) by enhancing the production of a naturally occurring substance in the body called nitric oxide.¹¹

More importantly, human clinical research¹² has demonstrated that 100 mg/day of resveratrol significantly reduced arterial stiffness (a major indicator of atherosclerosis) compared to placebo, and also lowered systolic blood pressure by 5.5 points in patients with type 2 diabetes. Another human study,¹³ which used a much higher dose (2.3 g) in older adults, found that resveratrol not only improved vascular function more than placebo, but also increased the number of mitochondria.those parts of the cells that help to generate energy for our body! Another interesting cardiovascular benefit is resveratrol’s effect on Apolipoprotein B (ApoB), a primary component of many lipoproteins such as LDL (the gbad cholesterolh) that are involved in atherosclerosis and cardiovascular disease. In human clinical research¹⁴ on overweight or obese individuals with mild hypertriglyceridemia, 1000 mg/day of resveratrol for one week followed by 2000 mg/day for two weeks reduced ApoB production rate by an impressive 22 percent. In addition, flow-mediated dilatation (a measure of arterial circulation and endothelial function) was increased in human studies^15,16,17 where 10 mg to 270 mg/day of resveratrol was given. In one of the studies,¹⁸ LDL cholesterol levels were also significantly decreased.

Inflammation
In addition to showing anti-inflammatory effects in in-vitro and animal studies, resveratrol has also been shown to comprehensively suppress oxidative and inflammatory stress with as little as 40 mg/day in normal human subjects.¹⁹ This included the reduction of inflammatory markers such as TNF-alpha, IL-6, and C-reactive protein, with no changes in the placebo group. Similarly, in postmenopausal women with osteoarthritis pain, 75 mg of resveratrol twice daily significantly reduced pain and improved total well-being.²⁰

Ulcerative colitis (UC), a chronic inflammatory bowel disease, has also responded to treatment with resveratrol. In one study²¹ with 56 UC patients, those receiving 500 mg/day of resveratrol had significant symptom improvement, reduced malondialdehyde (a highly reactive oxidative stress compound), and increased superoxide dismutase (SOD), and total antioxidant capacity. In another human study²² with 50 UC patients, 500 mg/day of resveratrol also reduced the activity of inflammatory compounds, including TNF-α, hs-CRP, and activity of NF-κB. Furthermore, in a study²³ of firefighters, supplementation with 100 mg/day resveratrol for 90 days, plasma biomarkers of inflammation were reduced after a physical fitness test, including IL-6 and TNF-α. This adds further credence to resveratrol’s anti-inflammatory effects.

Immune Health/Breast Cancer Prevention
Resveratrol’s effect on immune health can be as fundamental as increasing certain circulating immune cells, or as profound at reducing the risk of breast cancer. For example, human research²⁴ was conducted to assess the effects of repeated doses of resveratrol (1000 mg/day for 28 days) on circulating immune cells in healthy individuals. The results were that resveratrol was safe and well tolerated and was associated with significant increases in the numbers of circulating gamma delta T cells (functioning as a first line of defense and a bridge between innate and adaptive responses) and regulatory T cells—demonstrating that resveratrol has clear biological effects on human circulating immune cells.

With regard to breast cancer prevention, resveratrol may help in a couple of ways. First, resveratrol has been shown to have a dose-dependent effect on reducing the formation of mammary tumors in-vitro as a result of down-regulating DNA methyltransferases. To see if it had a similar effect in humans, a study²⁵ was conducted in which 39 adult women at increased breast cancer risk received a placebo, 5 or 50 mg of resveratrol twice daily for 12 weeks. Results were that there was indeed decrease in methylation of the tumor suppressor gene with increasing levels of resveratrol (P = .047).

In another study²⁶ of 34 overweight, postmenopausal women (BMI ≥ 25 kg/m2), the clinical effect of resveratrol on systemic sex steroid hormones were investigated, since high estrogen levels may contribute to breast cancer. The subjects received 1 g of resveratrol daily for 12 weeks. The results were that resveratrol supplementation led to an average of 73 percent increase in urinary 2-hydroxyestrone (the “good estrogen”) levels leading to a favorable change in estrogen ratios that are less conducive to the development of breast cancer. This research demonstrated that among overweight and obese postmenopausal women, a daily 1 g dose of resveratrol has favorable effects on estrogen metabolism.

Muscle Health
In a 12-week study,²⁷ older men and women (aged 65.80 years) exercised and took either a placebo or 500 mg/day of resveratrol to determine if resveratrol would have additive effects to those of exercise. Results showed that exercise added to resveratrol treatment increased the number of mitochondria, and improved muscle fatigue resistance more than placebo and exercise treatments. In addition, subjects treated with resveratrol had an increase in muscular torque and power after training, whereas exercise did not increase these parameters in the placebo-treated older subjects. Furthermore, exercise combined with resveratrol significantly improved muscle fiber. Together, these data suggest that resveratrol combined with exercise might provide a better approach for reversing sarcopenia than exercise alone.

Cognitive Health
Research suggests that resveratrol may have cognitive health benefits in people with and without dementia. For example, the ongoing dysfunction of small blood vessels in patients with type 2 diabetes mellitus (T2DM) may impair the ability of cerebral vessels to supply blood to various brain regions, thereby increasing risks of dementia. To determine if resveratrol could benefit cerebral circulation, a study²⁸ was conducted in which 36 dementia-free, non-insulin dependent T2DM older adults (49–78 years old) consumed single doses of resveratrol (0, 75, 150, and 300 mg) at weekly intervals. Results were that 75–300 mg of resveratrol enhanced vasodilator responsiveness in cerebral vessels.

In another study,²⁹ 80 post-menopausal women aged 45–85 years received resveratrol or placebo for 14 weeks to examine the effect on cognitive performance and other parameters. Results were that compared to placebo, significant improvements were observed in the performance of cognitive tasks in the domain of verbal memory (p = 0.041) and in overall cognitive performance (p = 0.020). Mood also tended to improve in multiple measures. These results indicate that regular consumption of a modest dose of resveratrol can enhance both cerebrovascular function and cognition in post-menopausal women, potentially reducing their heightened risk of accelerated cognitive decline and offering a promising therapeutic treatment for menopause-related cognitive decline.

To test³⁰ whether supplementation of resveratrol (200 mg/ day for 26 weeks) would enhance memory performance in older adults, 23 healthy overweight older individuals were pairwise matched to 23 participants that received placebo (total n = 46, 18 females, 50–75 years). Results showed a significant effect of resveratrol on retention of words over 30 min compared with placebo (p = 0.038), significant increases in hippocampal functional connectivity, decreases in glycated hemoglobin (HbA1c) and body fat, and increases in leptin compared with placebo (all p < 0.05). This study provides initial evidence that supplementary resveratrol improves memory performance in association with improved glucose metabolism in older adults, providing a basis for helping to maintain brain health during aging.

To determine the effects of oral resveratrol on localized cerebral blood flow, a study³¹ was conducted with which 22 healthy human adults received placebo and two doses (250 and 500 mg) of resveratrol in counterbalanced order on separate days. After a 45-min resting absorption period, the participants performed a selection of cognitive tasks. Resveratrol administration resulted in dose-dependent increases in cerebral blood flow during task performance, and enhanced oxygen extraction. These results showed that single doses of orally administered resveratrol can modulate cerebral blood flow variables.

Finally, a clinical study³² was conducted to determine if up to 1 g of resveratrol twice daily could benefit Alzheimer’s disease (AD) patients. The results demonstrated that resveratrol decreased CSF MMP9 (a biomarker for confirmed AD), modulates neuro-inflammation, and induces adaptive immunity— suggesting that resveratrol may be a viable target for treatment or prevention of neurodegenerative disorders.

Weight Loss
One of the reasons that resveratrol has received widespread interest is because of its ability to mimic effects of calorie restriction. To gain more insight into this effect on adipose tissue, a study³³ was conducted in which healthy obese subjects were supplemented with 150 mg/day of resveratrol or placebo for 30 days. Results showed that resveratrol significantly decreased the size of adipocytes (fat cells), with a shift toward reducing the proportion of large and very-large adipocytes and an increase in small adipocytes. Furthermore, lysosomal/phagosomal pathway and transcription factor EB were up-regulated reflecting an alternative pathway of lipid breakdown by autophagy.

Similarly,³⁴ T2DM patients received 3 g resveratrol or placebo daily for 12 weeks. Results were that there was a significant increase in both SIRT1 expression and resting metabolic rate compared with the placebo group. In patients with T2DM, treatment with resveratrol helped regulate energy expenditure, suggesting that resveratrol may have beneficial exercise-mimetic effects.

Again,³⁵ healthy, obese subjects were treated with placebo and 150 mg/day resveratrol for 30 days. The results were that resveratrol increased SIRT1 and improved the muscle’s use of fatty acids as an energy fuel, demonstrating that 30 days of resveratrol supplementation induces metabolic changes in obese humans, mimicking the effects of calorie restriction. Given these results, one might think that resveratrol may aid in weight loss—and indeed this has been shown to be the case in clinical research.

Orlistat is an over-the-counter drug (also known as Alli®) designed to treat obesity by reducing the absorption of fats from the human diet. A study³⁶ was conducted to evaluate the efficacy of combining orlistat with resveratrol in 84 obese subjects over a 6-month period. The subjects consumed a diet with 500 fewer calories than their usual diet for two weeks, and were randomly assigned to four groups, placebo, resveratrol, orlistat, or the O-R combination, and they consumed the energy-reduced diet for 6-months. Results were significant weight loss of 15 lbs in the O-R group compared with 7.7 lbs in the placebo group. Significant decreases in BMI, waist circumference, fat mass, triglycerides, leptin, and leptin/adiponectin ratio were observed with the O-R combination, indicating that it was the most effective weight loss treatment.

In another study,³⁷ 24 patients with metabolic syndrome received resveratrol (500 mg) three times per day before meals for 90 days. Resveratrol administration resulted in significant differences in total weight (P=0.007), body mass index (BMI) (P=0.006), fat mass (P=0.001), and waist circumference (P=0.004). In conclusion, administration of resveratrol significantly decreased weight, BMI, and fat mass.

Blood Sugar/Insulin Resistance
A study³⁸ was conducted using 480 mg/day of resveratrol or placebo for four weeks on 43 patients with diabetes who also had chronic periodontitis (i.e. gum disease). Results were that serum levels of fasting insulin and insulin resistance were significantly lower in the resveratrol group compared with control group. With regard to periodontal disease, there was also a significant difference in the gum pocket depth between intervention and control groups with resveratrol. The researchers recommended that resveratrol supplementation might be beneficial as adjuvant therapy along with non-surgical periodontal treatment in insulin resistance and improving periodontal status among patients with diabetes with periodontal disease.

Another human clinical trial³⁹ was conducted in 32 over-weight, older adults (average age: 73 years). Participants received placebo, 300 mg/day of resveratrol, or 1000 mg/day of resveratrol for 90 days. Results were that, compared to placebo, glucose levels were significantly lower at after treatment among participants receiving either dose of resveratrol (P<0.05), and were well tolerated.

In this study,⁴⁰ 62 patients with T2DM received either an oral hypoglycemic medication, or an oral hypoglycemic medication along with 250 mg/day of resveratrol. Results were that supplementation with resveratrol for three months significantly improved the mean hemoglobin A1c (P<0.05), a measure of long-term glucose control, systolic blood pressure (P<0.05), total cholesterol (P<0.05), and total protein (P<0.05) in T2DM. The researchers concluded that oral supplementation with resveratrol was effective in improving glycemic control and may be a potential adjuvant for the treatment and management of diabetes.

In a pilot study,⁴¹ subjects with impaired glucose tolerance (aged 72 ± 3 years) received 1, 1.5, or 2 g/day of resveratrol for four weeks. After four weeks of resveratrol supplementation, results showed that post-meal (P=0.003) and 3-hour glucose levels (P=0.001) declined. Researchers concluded that, at doses between 1 and 2 g/day, resveratrol improves insulin sensitivity and post-meal plasma glucose in subjects with impaired glucose tolerance. Likewise, in a 4-week study,⁴² T2DM patients received 10 mg/day resveratrol or a placebo. Results showed that, after the fourth week, resveratrol significantly improved insulin sensitivity, which might be due to a resveratrol-induced decrease in oxidative stress that leads to a more efficient insulin-signaling pathway.

Non-Alcoholic Fatty Liver Disease
Nonalcoholic fatty liver disease (NAFLD) refers to the accumulation of fat in the liver of people who drink little or no alcohol. Unfortunately, NAFLD is common—with easily one-third of all American adults being affected⁴³—and often causes no signs and symptoms, and sometimes no complications. In more serious cases, however, the fat that accumulates in NAFLD can cause liver inflammation and scarring.⁴⁴ In addition, NAFLD is usually associated with insulin resistance, central obesity, reduced glucose tolerance, T2DM and high triglyceride levels.

In a clinical study,⁴⁵ 50 NAFLD patients received either a 500 mg/day of resveratrol or a placebo for 12 weeks. Both groups were advised to follow an energy-balanced diet and physical activity recommendations. Results were that resveratrol supplementation reduced alanine aminotransferase (a marker for NAFLD) and hepatic steatosis (fatty liver) significantly more than placebo (P<0E05).

In another study,⁴⁶ 60 NAFLD patients received two 150 mg resveratrol capsules twice daily for three months. Results were that, compared with the placebo group, resveratrol significantly decreased aspartate aminotransferase, glucose and low-density lipoprotein cholesterol (P.0.001) alanine aminotransferase, total cholesterol (P=0.002), and insulin resistance (P=0.016). The researchers concluded that resveratrol supplementation might benefit patients with NAFLD.

Other Resveratrol Benefits
In addition to the aforementioned applications for resveratrol, there are additional benefits for this nutraceutical as well. Two such benefits are related to bone health, and for those who are smokers.

In a clinical study,⁴⁷ 66 middle-aged, obese subjects with metabolic syndrome (average age: 49.3 } 6.3 years) received oral treatment with 1,000 mg or 150 mg of resveratrol, or a placebo daily for 16 weeks to assess changes in the bone turnover marker bone alkaline phosphatase (BAP), and bone mineral density (BMD). Results were that BAP increased dose dependently with resveratrol (P<0.001), compared with placebo. Lumbar spine trabecular volumetric bone mineral density also increased dose dependently with resveratrol (P=0.036), with a significant increase of 2.6 percent in the 1,000 mg resveratrol group compared with placebo (P=0.043). In addition, changes in BAP and bone mineral density were positively correlated (P=0.027).

Smokers typically experience a state of low-grade systemic inflammation and oxidant-antioxidant imbalance. To determine whether resveratrol has beneficial effects on markers of inflammation and oxidative stress, a study⁴⁸ was conducted with 50 healthy adult smokers who alternatively were given 500 mg/ day of resveratrol and placebo. Results were that resveratrol significantly reduced the inflammatory marker C-reactive protein (CRP), triglyceride concentrations, and increased Total Antioxidant Status (TAS) values. The researchers concluded that, because resveratrol has anti-inflammatory, anti-oxidant, and hypotriglyceridemic effects, its supplementation might beneficially affect the increased cardiovascular risk of healthy smokers.

Improving The Bioavailability And Efficacy Of Resveratrol

Now that we’ve reviewed some of the many benefits associated with resveratrol supplementation, let’s briefly consider ways to improve the bioavailability and efficacy of this valuable nutraceutical. First, take resveratrol on an empty stomach. The reason for this recommendation is a study showing that the absorption rate of resveratrol following an oral 400 mg single dose was significantly delayed by the presence of food.⁴⁹

Second, resveratrol may work better when taken together with pterostilbene (a related antioxidant) and quercetin (a flavonoid). In this study,⁵⁰ the antioxidant activities of resveratrol, pterostilbene and quercetin, and the effect of their combination were investigated in human blood cells in-vitro. When used together, the combination protected the blood cells against destruction and against depletion of the important antioxidant, glutathione. Also, the combination of resveratrol with quercetin or pterostilbene synergistically inhibited oxidative injury of membrane lipids. These protective effects may partially explain the health benefit of these bioactive micro-components when together in the diet.

Conclusion
The value of supplementation with resveratrol has moved beyond the “French paradox” and the activation of the SIRT 1 gene, associated with longevity. Human clinical research has demonstrated efficacy of resveratrol for inflammation, immune health/breast cancer prevention, muscle health, cognitive health, weight loss, blood sugar/insulin resistance, non-alcoholic fatty liver disease, and more.

Endnotes

1. Labinskyy N, Csiszar A, Veress G, Stef G, Pacher P, Oroszi G, Wu J, Ungvari Z. Vascular dysfunction in aging: potential effects of resveratrol, an anti-inflammatory phytoestrogen. Current Medicinal Chemistry 2006; 13(9):989–96.
2. Borra MT, Smith BC, Denu JM.Mechanism of human SIRT1 activation by resveratrol. J Biol Chem. 2005 Apr 29;280(17):17187–95. 3. Higdon J, Drake VJ, Steward WP. Resveratrol. Micronutrient Information Center. Linus Pauling Institute, Oregon State University, Corvallis, OR; 2016.
3. Fremont L. Biological Effects of Resveratrol. Life Sci. 2000;66(8):663–73.
4. Soleas GJ, Diamandis EP, Goldberg DM. Resveratrol: A molecule whose time has come? And gone? Clin Biochem 1997;30:91–113.
5. Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nature reviews. Drug Discovery 2006; 5(6):493–506.
6. Bradamante S, Barenghi L, Villa A. Cardiovascular protective effects of resveratrol. Cardiovasc Drug Rev 2004; 22(3):169–188.
7. Apostolidou C, Adamopoulos K, Iliadis S, Kourtidou-Papadeli C. Alterations of antioxidant status in asymptomatic hypercholesterolemic individuals after resveratrol intake. Int J Food Sci Nutr. 2015 Aug;67(5):541–52.
8. Anisimova NY, Kiselevsky MV, Sosnov AV, Sadovnikov SV, Stankov IN, Gakh AA. Trans-, cis-, and dihydro-resveratrol: a comparative study. Chem Cent J. 2011 Dec 20;5:88.
9. Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nature reviews. Drug Discovery 2006; 5(6):493–506.
10. Wallerath T, Deckert G, Ternes T, et al. Resveratrol, a polyphenolic phytoalexin present in red wine, enhances expression and activity of endothelial nitric oxide synthase. Circulation 2002; 106(13):1652–8.
11. Imamura H, Yamaguchi T, Nagayama D, Saiki A, Shirai K, Tatsuno I. Resveratrol Ameliorates Arterial Stiffness Assessed by Cardio-Ankle Vascular Index in Patients With Type 2 Diabetes Mellitus. Int Heart J. 2017 Aug 3;58(4):577–83.
12. Pollack RM, Barzilai N, Anghel V, Kulkarni AS, Golden A, O’Broin P, Sinclair DA, Bonkowski MS, Coleville AJ, Powell D, Kim S, Moaddel R, Stein D, Zhang K, Hawkins M, Crandall JP. Resveratrol Improves Vascular Function and Mitochondrial Number but Not Glucose Metabolism in Older Adults. J Gerontol A Biol Sci Med Sci. 2017 Nov 9;72(12):1703–9.
13. Dash S, Xiao C, Morgantini C, Szeto L, Lewis GF. High-dose resveratrol treatment for 2 weeks inhibits intestinal and hepatic lipoprotein production in overweight/obese men. Arterioscler Thromb Vasc Biol. 2013 Dec;33(12):2895–901.
14. Wong RH, Berry NM, Coates AM, Buckley JD, Bryan J, Kunz I, Howe PR. Chronic resveratrol consumption improves brachial flow-mediated dilatation in healthy obese adults. J Hypertens. 2013 Sep;31(9):1819–27.
15. Magyar K, Halmosi R, Palfi A, Feher G, Czopf L, Fulop A, Battyany I, Sumegi B, Toth K, Szabados E. Cardioprotection by resveratrol: A human clinical trial in patients with stable coronary artery disease. Clin Hemorheol Microcirc. 2012;50(3):179–87.
16. Wong RH1, Howe PR, Buckley JD, Coates AM, Kunz I, Berry NM. Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure. Nutr Metab Cardiovasc Dis. 2011 Nov;21(11):851–6.
17. Magyar K, Halmosi R, Palfi A, Feher G, Czopf L, Fulop A, Battyany I, Sumegi B, Toth K, Szabados E. Cardioprotection by resveratrol: A human clinical trial in patients with stable coronary artery disease. Clin Hemorheol Microcirc. 2012;50(3):179–87.
18. Ghanim H, Sia CL, Abuaysheh S, Korzeniewski K, Patnaik P, Marumganti A, Chaudhuri A, Dandona P. An antiinflammatory and reactive oxygen species suppressive effects of an extract of Polygonum cuspidatum containing resveratrol. J Clin Endocrinol Metab. 2010 Sep;95(9):E1-8.
19. Wong RHX, Evans HM, Howe PRC. Resveratrol supplementation reduces pain experience by postmenopausal women. Menopause. 2017 Aug;24(8):916–22.
20. Samsamikor M, Daryani NE, Asl PR, Hekmatdoost A. Resveratrol Supplementation and Oxidative/Anti-Oxidative Status in Patients with Ulcerative Colitis: A Randomized, Double-Blind, Placebo-controlled Pilot Study. Arch Med Res. 2016 May;47(4):304–9.
21. Samsami-Kor M, Daryani NE, Asl PR, Hekmatdoost A. Anti-Inflammatory Effects of Resveratrol in Patients with Ulcerative Colitis: A Randomized, Double-Blind, Placebo-controlled Pilot Study. Arch Med Res. 2015 May;46(4):280–5.
22. Macedo RC, Vieira A1, Marin DP2, Otton R3. Effects of chronic resveratrol supplementation in military firefighters undergo a physical fitness test–a placebo-controlled, double blind study. Chem Biol Interact. 2015 Feb 5;227:89–95.
23. Espinoza JL, Trung LQ, Inaoka PT, Yamada K, An DT, Mizuno S, Nakao S, Takami A. The Repeated Administration of Resveratrol Has Measurable Effects on Circulating T-Cell Subsets in Humans. Oxid Med Cell Longev. 2017;2017:6781872.
24. Zhu W, Qin W, Zhang K, Rottinghaus GE, Chen YC, Kliethermes B, Sauter ER. Trans-resveratrol alters mammary promoter hypermethylation in women at increased risk for breast cancer. Nutr Cancer. 2012 Apr;64(3):393–400.
25. Chow HH, Garland LL, Heckman-Stoddard BM, Hsu CH, Butler VD, Cordova CA, Chew WM, Cornelison TL. A pilot clinical study of resveratrol in postmenopausal women with high body mass index: effects on systemic sex steroid hormones. J Transl Med. 2014 Aug 14;12:223.
26. Alway SE, McCrory JL, Kearcher K, Vickers A, Frear B, Gilleland DL, Bonner DE, Thomas JM, Donley DA, Lively MW, Mohamed JS. Resveratrol Enhances Exercise-Induced Cellular and Functional Adaptations of Skeletal Muscle in Older Men and Women. J Gerontol A Biol Sci Med Sci. 2017 Nov 9;72(12):1595–1606.
27. Wong RH, Nealon RS, Scholey A, Howe PR. Low dose resveratrol improves cerebrovascular function in type 2 diabetes mellitus. Nutr Metab Cardiovasc Dis. 2016 May;26(5):393–9.
28. Evans HM, Howe PR, Wong RH. Effects of Resveratrol on Cognitive Performance, Mood and Cerebrovascular Function in Post-Menopausal Women; A 14-Week Randomised Placebo-Controlled Intervention Trial. Nutrients. 2017 Jan 3;9(1). pii: E27.
29. Witte AV, Kerti L, Margulies DS, Flöel A. Effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults. J Neurosci. 2014 Jun 4;34(23):7862–70.
30. Kennedy DO, Wightman EL, Reay JL, Lietz G, Okello EJ, Wilde A, Haskell CF. Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation. Am J Clin Nutr. 2010 Jun;91(6):1590–7.
31. Moussa C, Hebron M, Huang X, Ahn J, Rissman RA, Aisen PS, Turner RS. Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer’s disease. J Neuroinflammation. 2017 Jan 3;14(1):1.
32. Konings E, Timmers S, Boekschoten MV, Goossens GH, Jocken JW, Afman LA, Müller M, Schrauwen P, Mariman EC, Blaak EE. The effects of 30 days resveratrol supplementation on adipose tissue morphology and gene expression patterns in obese men. Int J Obes (Lond). 2014 Mar;38(3):470–3.
33. Goh KP, Lee HY, Lau DP, Supaat W, Chan YH, Koh AF. Effects of resveratrol in patients with type 2 diabetes mellitus on skeletal muscle SIRT1 expression and energy expenditure. Int J Sport Nutr Exerc Metab. 2014 Feb;24(1):2–13.
34. Timmers S, Konings E, Bilet L, Houtkooper RH, van de Weijer T, Goossens GH, Hoeks J, van der Krieken S, Ryu D, Kersten S, Moonen-Kornips E, Hesselink MKC, Kunz I, Schrauwen-Hinderling VB, Blaak E, Auwerx J, Schrauwen P. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab. 2011 Nov 2;14(5):612–22.
35. Arzola-Paniagua MA, García-Salgado López ER, Calvo-Vargas CG, Guevara-Cruz M. Efficacy of an orlistat-resveratrol combination for weight loss in subjects with obesity: A randomized controlled trial. Obesity (Silver Spring). 2016 Jul;24(7):1454–63.
36. Méndez-del Villar M, González-Ortiz M, Martínez-Abundis E, Pérez-Rubio KG, Lizárraga-Valdez R. Effect of resveratrol administration on metabolic syndrome, insulin sensitivity, and insulin secretion. Metab Syndr Relat Disord. 2014 Dec;12(10):497–501.
37. Zare Javid A, Hormoznejad R, Yousefimanesh HA, Zakerkish M, Haghighi-Zadeh MH, Dehghan P, Ravanbakhsh M. The Impact of Resveratrol Supplementation on Blood Glucose, Insulin, Insulin Resistance, Triglyceride, and Periodontal Markers in Type 2 Diabetic Patients with Chronic Periodontitis. Phytother Res. 2017 Jan;31(1):108–114.
38. Anton SD, Embry C, Marsiske M, Lu X, Doss H, Leeuwenburgh C, Manini TM. Safety and metabolic outcomes of resveratrol supplementation in older adults: results of a twelve-week, placebo-controlled pilot study. Exp Gerontol. 2014 Sep;57:181–7.
39. Bhatt JK, Thomas S, Nanjan MJ. Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus. Nutr Res. 2012 Jul;32(7):537–41.
40. Crandall JP, Oram V, Trandafirescu G, Reid M, Kishore P, Hawkins M, Cohen HW, Barzilai N. Pilot study of resveratrol in older adults with impaired glucose tolerance. J Gerontol A Biol Sci Med Sci. 2012 Dec;67(12):1307–12.
41. Brasnyó P, Molnár GA, Mohás M, Markó L, Laczy B, Cseh J, Mikolás E, Szijártó IA, Mérei A, Halmai R, Mészáros LG, Sümegi B, Wittmann I. Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients. Br J Nutr. 2011 Aug;106(3):383–9.
42. Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, Grundy SM, Hobbs HH. Prevalence of hepatic steatosis in an urban population in the United States: Impact of ethnicity. Hepatology 2004;40(6):1387–95.
43. Sanyal AJ. American Gastroenterological Association: AGA technical review on nonalcoholic fatty liver disease (national guidelines). Gastroenterology 2002; 123:1705–25.
44. Faghihzadeh F, Adibi P, Hekmatdoost A. The effects of resveratrol supplementation on cardiovascular risk factors in patients with non-alcoholic fatty liver disease: a randomised, double-blind, placebo-controlled study. Br J Nutr. 2015 Sep 14;114(5):796–803.
45. Chen S, Zhao X, Ran L, Wan J, Wang X, Qin Y, Shu F, Gao Y, Yuan L, Zhang Q, Mi M. Resveratrol improves insulin resistance, glucose and lipid metabolism in patients with non-alcoholic fatty liver disease: a randomized controlled trial. Dig Liver Dis. 2015 Mar;47(3):226–32
46. Ornstrup MJ, Harsløf T, Kjær TN, Langdahl BL, Pedersen SB. Resveratrol increases bone mineral density and bone alkaline phosphatase in obese men: a randomized placebo-controlled trial. J Clin Endocrinol Metab. 2014 Dec;99(12):4720–9.
47. Bo S, Ciccone G, Castiglione A, Gambino R, De Michieli F, Villois P, Durazzo M, Cavallo-Perin P, Cassader M.Anti-inflammatory and antioxidant effects of resveratrol in healthy smokers a randomized, double-blind, placebo-controlled, cross-over trial. Curr Med Chem. 2013;20(10):1323–31.
48. Vaz-da-Silva M, Loureiro AI, Falcao A, Nunes T, Rocha JF, Fernandes-Lopes C, Soares E, Wright L, Almeida L, Soares-da-Silva P. Effect of food on the pharmacokinetic profile of trans-resveratrol. Int J Clin Pharmacol Ther. 2008 Nov;46(11):564–70.
49. Mikstacka R, Rimando AM, Ignatowicz E. Antioxidant effect of trans-resveratrol, pterostilbene, quercetin and their combinations in human erythrocytes in vitro. Plant Foods Hum Nutr. 2010 Mar;65(1):57–63

The post Resveratrol: A Research Review appeared first on Total Health Magazine.

The pungent taste of garlic is not to everyone’s liking, as its odor may remain on the breath and skin for days; moreover, large quantities of ingested garlic, potentially needed to boost immunity may cause gastrointestinal disturbances. The supplement Aged Garlic Extract^TM (Kyolic® AGE^TM) that is odorless, has become a most popular preparation that provides the benefits of garlic, including boosting immunity, without the unpleasant side effects. Moreover, its efficacy and reliable standing as the preferred garlic formulation for research on the health benefits of garlic, has yielded over 700 peer reviewed research publications in scientific and medical journals.

Aged Garlic Extract
The manufacturing of AGE, by Wakunaga of America, consists of harvesting organically grown garlic, and carrying out a procedure of extraction and aging, at room temperature, for 20 months The process converts harsh volatile compounds such as allicin to stable substances, thereby increasing antioxidant levels in AGE above levels found in fresh garlic.

Among the many components in AGE the major ones are organosulfur antioxidants, largely water soluble, and highly bioavailable including S-Allyl cysteine and S-Allyl mercaptocysteine. Also present are lipid soluble organosulfur compounds, carbohydrates, including fructans, which are immuo-boosters, micronutrients such as selenium and other antioxidants such as fructosyl arginine and alixin. The high antioxidant level in AGE prevent the damage induced by free radicals that are generated in metabolism and enhanced by environmental factors, such as radiation of different types including UV light from the sun and UV machines. Free radical damage plays a role in inflammation, and various pathological conditions including heart disease, dementia and cancer, so that the inhibition of free radicals by AGE is part of its action in helping prevent these pathological conditions, in part by boosting immunity.

Our Immune System
A healthy immune system is the secret to good health, protecting against infectious bacteria, viruses, fungi and helping block the development of cancer. A weak immune system exposes us to the damaging effects of infectious bacteria and viruses around us, from direct contact, exposure to a cough or a sneeze, from contaminated food and a wide range of sources that trigger serious illnesses, that may lead to death.

The immune system is complex and multilayered. Inflammation is one of the first responses of the immune system to infection and involves the release of substances called prostaglandins and leukotrienes that attract white blood cells (leukocytes) and interferons, that have anti-viral effects.

Among the white cells, the leukocytes there exist B and T lymphocytes. There are subtypes of T cells: killer T cell that kill cells infected with pathogens and helper T cell that regulate the immune response. Killer T cells kill cells that are infected with viruses (and other pathogens), or are otherwise damaged or dysfunctional. Helper T cells regulate the immune responses directing other cells to perform various tasks. Natural killer cell (NK) have in their power to kill tumor cells. Another group of lymphocytes are ãä-T cells that share the characteristics of helper T cells, killer T cells and NK cells.

AGE Enhances Immunity
Aged Garlic Extract has been shown in preclinical and clinical studies to enhance the immune response, mitigate infectious diseases, and kill cancer cells. AGE intake has been shown to increase the phagocytic (cell-killing) activity of macrophages, the activity of the T lymphocytes and increase the number and action of natural killer cells (NK) and antitumor action; AGE also was found to inhibit the allergy-causing histamine release and have anti-inflammatory effects, suppressing prostaglandins and enhancing interferon.

AGE Increases NK Activity
In a random double-blind clinical trial, Ishikawa and colleagues found that AGE given to patients with colorectal, liver or pancreatic cancer resulted in a significant increase in the number and activity of the NK cells, killing cancer cells.

Advanced-cancer patients with a decline in immune functions and quality of life, with inoperable colorectal, liver, or pancreatic cancer were recruited for the study. In a randomized six month double-blind trial, AGE was given to one group and a placebo to another. The patients consisted of 42 with liver cancer (84 percent), seven patients with pancreatic cancer (14 percent), and one patient with colon cancer (two percent). The study showed that both the number of NK cells and the NK cell activity increased significantly in the AGE group; showing that the administration of AGE to patients with advanced cancer of the digestive system has the potential to improve the anti-tumor NK cell activity.

AIDS patients show lower levels of NK cells. Abdullah and colleagues showed that a six week intake of AGE at 1800 mg/day increased the levels of NK cells to that of healthy individuals; Helper T cells were also increased and patients showed an improvement of several pathological conditions, including herpes virus infection, yeast infections and diarrhea; Comparing the efficacy of AGE to that of fresh garlic, investigators found that AGE was more effective as an immune-stimulator than fresh garlic; NK activity was increased by 160 percent with the intake of AGE capsules compared with an increase of 140 percent in patients taking the fresh garlic preparation.

AGE Helps Reduce Colds And Flu
A randomized, double-blind, placebo-controlled study recruited 120 healthy subjects (60 per group between ages of 21 and 50) and evaluated the effect of AGE supplementation (2.56 g/d) on the proliferation of immune cells and cold and flu symptoms.

After 45 days of intake of an encapsulated Aged Garlic Extract, NK and £^£_-T cells rose in number, compared to placebo. Following 90 days of supplementation, diary entries of illness showed that though the incidence of colds and flu, were not statistically different, the group consuming Aged Garlic Extract showed a reduced severity of both colds and flu noted by a reduction in the number of reported symptoms (21 percent fewer) and by a reduction in the number of days (61 percent fewer), and incidences (58 percent fewer) where the subjects¡¦ function was sub optimal.

The investigators concluded that supplementation of the diet with AGE may enhance immune cell function and potentially reduce inflammation, resulting in a reduced severity of colds and flu.

AGE Blocks Ultraviolet-Induced Immunosuppression.
Studies on human volunteers in Australia found that exposure to ultraviolet radiation (UV) causes immunosuppression resulting in an increase skin cancer frequency. There was a gender difference. UV doses that caused immunosuppression in men were three times lower than those causing immunosuppression in women. The investigators concluded that this phenomenon might underlie the higher incidence of skin cancer and mortality observed in the male population.

In a preclinical study, where the immune response as measured by contact hypersensitivity, Reeve and colleagues found that immunosuppression of 58 percent induced by a moderate exposure to UVB radiation was reduced to 19 percent by a diet containing AGE, at 4 percent of the diet. The preclinical studies suggest that AGE may help protect humans against immunosuppression induced by exposure to UV, and therefore have a potential to reduce the risk of UV induced skin cancer, for example by lengthy exposures to the sun.

AGE Reduces Inflammatory Prostaglandins
Oxidative damage by free radicals and immune-inflammatory activation are considered important factors in the development of cancer, neurodegenerative and cardiovascular diseases. Prostaglandins are substances associated with inflammation in that the release of local pro-inflammatory prostaglandins takes place, accompanied by the destruction of tissue. Rahman and colleagues have shown that dietary supplementation with AGE for 14 days reduced the plasma and urine levels of prostaglandin 8-iso-PGF (2 alpha) by 29 and 37 percent, respectively in nonsmokers and by 35 and 48 percent, respectively in smokers.

By stopping the intake of AGE, they found that in both groups, smokers and non smokers, the plasma and urine concentrations of prostaglandins reversed to values that were no different from those before ingestion of AGE, within fourteen days after cessation of the dietary supplementation. The study shows that a continuous intake of AGE is required to maintain the reduced levels of inflammatory prostaglandins.

The Bottom Line
Aged Garlic Extract is a powerful wide ranging health supplement that plays a role in helping enhance immunity and thus helping protect against diseases and conditions that involve inflammation and weakening of the immune system; such conditions have been reported to be associated with cancer development, neurodegenerative and cardiovascular disease as well as aging. In over 700 medical and scientific studies in both preclinical and clinical studies, AGE has shown its capacity to help reduce disease and maintain health.

References

1. Nantz MP, Rowe CA, Muller CE et al Supplementation with aged garlic extract improves both NK and Υδ-T cell function and reduces the severity of cold and flu symptoms: a randomized, double-blind, placebo-controlled nutrition intervention. J Nutr. 2012; 31:337—44.
2. Borek C. Dietary antioxidants and human cancer. Integr Cancer Ther. 2004;3:333—41.
3. Reeve VE1, Bosnic M, Rozinova E, Boehm-Wilcox C. A garlic extract protects from ultraviolet B (280¡V320 nm) radiation-induced suppression of contact hypersensitivity. Photochem Photobiol. 1993;58:813—7.
4. Dillon SA, Lowe GM, Billington D, Rahman K. Dietary supplementation with aged garlic extract reduces plasma and urine concentrations of 8-iso-prostaglandin F(2 alpha) in smoking and nonsmoking men and women. J Nutr. 2002 ;132:168—71.
5. Ishikawa H, Saeki T, Otani T, Suzuki T, Shimozuma K, Nishino H, Fukuda S, Morimoto K. Aged garlic extract prevents a decline of NK cell number and activity in patients with advanced cancer. J Nutr. 2006;136:816S—820S
6. Abdullah TH, Kirkpatrick DV, Carter J. Enhancement of natural killer activity in AIDS with garlic. J Oncology. 1989;21:52—3.

The post Garlic and Aged Garlic Extract Immunity Boosters appeared first on Total Health Magazine.

While we enjoy garlic in small quantities as an excellent condiment, ingesting large amounts of fresh garlic to achieve its anti-aging benefits is not for everyone. Garlic’s strong odor lingers on the breath and skin and ingesting large quantities may lead to gastrointestinal problems, including flatulence and diarrhea. Kyolic^TM AGE, (aged garlic extract), an odorless supplement provides the benefits of the fresh bulb without the unpleasant side effects. AGE has been the choice garlic preparation in scientific and medical research on the health effects of garlic and its benefits have been documented in over 700 peer reviewed publications.

Aged Garlic Extract
Kyolic Aged Garlic Extract (AGE), is manufactured by Wakunaga of America, from organically grown garlic by a lengthy procedure of extraction and aging, at room temperature. The process converts harsh unstable substances such as allicin to stable compounds, increasing the antioxidant content of AGE above the levels found in fresh garlic.

AGE is rich in highly bioavailable organosulfur compounds with antioxidant activity, largely water soluble, including S-allyl cysteine and S-allyl mercaptocysteine. Also present are lipid soluble organosulfur compounds, carbohydrates, including fructans which are immune-boosters and micronutrients such as selenium and other antioxidants such as fructosyl arginine and alixin.

AGE had been shown to enhance immunity, reduce inflammation, lower cholesterol and blood pressure and help reduce the risk of cardiovascular and cerebrovascular diseases, cancer, neurodegenerative diseases, help maintain bone density as well as prevent cell damage by free radical-producing drugs and radiation, including UV.

Protecting Immunity
Our immune system is the path to good health and longevity. A vigorous immune system protects against infectious bacteria, viruses, fungi and helps fight the development of cancer. Our goal is therefore to maintain a fortified immune system to protect us from colds and flu, fight invading disease-causing microorganisms, prevent cancer growth and combat inflammation, now known to play a critical role in cardiovascular disease as well as in cancer and neurodegenerative diseases. In most cases our immune system can handle an amazing variety of pathogens and microbes and overcome inflammation, but as a battle between a pathogen and the immune response takes place, the result can be sickness, when immunity is weak, or health, when the immune cells are winning.

The immune system is complex. Inflammation is one of the first responses of the immune system to infection and involves the release of prostaglandins and leukotrienes that attract white blood cells (leukocytes), and interferons that has anti-viral effects.

Leukocytes include a wide range of immune cells that include macrophages, neutrophils, that engulf foreign invaders and natural killer cells (NK) that destroy cancer cells and cells infected by viruses.

AGE Enhances Immunity
Aged garlic extract has been shown in a wide range of preclinical and clinical studies to enhance the immune response, mitigate infectious diseases, reduce inflammation and kill cancer cells. AGE intake enhances the phagocytic (cell-killing) activity of macrophages, the activity of the T lymphocytes that direct the immune system to combat invaders, increases the number and activity of natural killer cells (NK) and their anti-cancer action; AGE also was found to, suppress inflammation—related prostaglandins and enhance interferon.

AGE Increases NK Activity
A random double-blind clinical trial showed that AGE administered to patients with inoperable colorectal, liver or pancreatic cancer resulted in a significant increase in the number and activity of the NK cells.

A study in AIDS patients, who are found to have lower levels of NK cells showed that AGE enhanced NK cells and helper T cells. After a 6-week intake of AGE at 1800 mg/day the levels of NK cells rose to that of the healthy individuals. Helper T cells were also increased with patients showing improvement of a variety of conditions, often increased in aging, including herpes infection, yeast infections and diarrhea; when compared to the efficacy of fresh garlic, the investigators found that AGE was a more effective immune-stimulator than fresh garlic, and observed NK activity was up by 140 percent with the fresh preparation and by 160 percent with AGE capsules.

AGE Prevents UV induced Immunosuppression
Ultra violet radiation (UV) has been linked to cancer, largely skin cancer; one of the effects of UV is to decrease immunity. Studies in Australia on human volunteers have shown immunosuppression by exposure to UV irradiation and that this immunosuppression increases the incidence of skin cancer. Men were immunosuppressed by UV doses that were three times lower than those required to immunosuppress women. They concluded that this may be an important cause of the higher skin cancer incidence and mortality observed in men.

In a preclinical study, using contact hypersensitivity as the immune response, Reeve and colleagues found a 58 percent immunosuppression following moderate exposure to UVB radiation, direct DNA damage was reduced to 19 percent by intake of AGE as four percent of the diet. The pre-clinical studies offer the possibility that AGE may also help protect humans against UV induced immunosuppression, and have the potential to reduce the risk of skin cancer a condition that is more prevalent in aging.

AGE Reduces Inflammatory Prostaglandins
Oxidative damage and immune-inflammatory activation play a role in cancer, neurodegenerative disease, cardiovascular disease and in depression. Prostaglanding, are associated with inflammation and release of local pro-inflammatory prostaglandins and cytokines, accompanied by the destruction of tissue. Rahman and colleagues have found that dietary supplementation with AGE for 14 days reduced plasma and urine concentrations of the prostaglandin 8iso-PGF(2 alpha) by up to 37 percent in nonsmokers and up to 48 percent in smokers. Fourteen days after cessation of dietary supplementation, prostaglandin levels returned to similar levels as those before ingestion of AGE, showing that in order to maintain protection a continuous intake of AGE is required.

AGE Protects The Heart And Brain
Aged garlic extract has been shown to modulate cardiovascular risk factors in over 700 scientific and medical publications. The AGE protective action also reduced risk factors for dementia. AGE increases, by 30-40 percent, the production of nitric oxide (NO), a regulator of blood pressure and lowers blood pressure, thus protecting both the heart and the brain. AGE inhibits platelet aggregation and adhesion that play a role in atherosclerotic plaque formation, it lowers LDL and prevents its oxidation, reduces triglycerides and homocysteine. AGE elevates HDL cholesterol (the good cholesterol), and reduces smoking related oxidative damage.

The major effect of AGE in lowering cholesterol is by blocking an enzyme involved in the production of cholesterol (3 hydroxy 3 methylglutaryl CoA) by as much as 41 percent. The effect is additive with statins, the cholesterol lowering medications. Breakthrough clinical studies at the University of California Los Angeles, found that AGE significantly inhibits the progression of coronary artery calcification, a marker for atherosclerosis, thus reducing the risk of plaque formation and a heart attack. The same studies, authored by Dr. Budoff and colleagues also showed that AGE lowers homocysteine triglycerides and LDL cholesterol, and increases HDL.

Protection Of Blood Vessels
One of the age related cardiovascular problems is the narrowing of blood vessels due to calcification of the lining. AGE protects the lining of blood vessels (endothelial cells) from oxidative damage and increases microcirculation; an important factor in cardio-protection, notably in diabetes, where the disease damages microvasculature and the risk of cardiovascular disease and dementia is high.

The Bottom Line
Kyolic aged garlic extract (AGE) is a natural, odorless antioxidant-rich garlic supplement, manufactured by Wakunaga of America from organic garlic. It is the most popular garlic supplement and being the most standardized is the preferred form used in medical and scientific research. AGE has consistently shown an ability to act as an effective health promoting supplement with anti-aging activity, boosting immunity, reducing inflammation, lowering risk factors for cardiovascular disease, dementia and cancer as well as helping maintain bone density, an important consideration in aging as bone fragility increases with age.

References

1. Zeb I, Ahmadi N, Nasir K, Kadakia J, Larijani VN, Flores F, Li D, Budoff MJ, Aged garlic extract and coenzyme Q10 have favorable effect on inflammatory markers and coronary atherosclerosis progression: A randomized clinical trial. J Cardiovasc Dis Res. 2012 :185¡V90.
2. Borek C. Garlic reduces dementia and heart disease risk J Nut. 2006;136:810¡V812.
3. Nasser A. et al Aged garlic extract with supplement is associated with beneficial effects on bone mineral density and predicts lack of progression of atherosclerosis: a prospective double blinded randomized trial 2015; Int J. of Cardiovascular Research 4:3 http://dx.doi.org/10.4172/2324-8602.1000206.
4. Dillon SA, Lowe GM, Billington D, Rahman K. Dietary supplementation with aged garlic extract reduces plasma and urine concentrations of 8-iso prostaglandin F(2alpha). J Nutr. 2002 Feb;132 :168¡V71.
5. Tanaka S, Haruma K, Yoshihara M, Kajiyama G, Kira K, Amagase H, Chayama K. Aged garlic extract has potential suppressive effect on colorectal adenoma in humans. J Nutr. 2006 Mar;136 :821S¡V826S.
6. Ishikawa H, Saeki T, Otani T, Suzuki T, Shimozuma K, Nishino H, Fukuda S, Morimoto K. Aged garlic extract prevents a decline of NK cell number and activity in patients with advanced cancer J Nutr. 2006 Mar;136 :816S-820S.

The post Kyolic Aged Garlic Extract: Anti-Aging Boost appeared first on Total Health Magazine.