The term antioxidant has become a mainstay in the lexicon of the natural products industry. Furthermore, as I pointed out in an article last year from this same issue of Vitamin Retailer magazine, over the past few decades the choices for nutraceutical antioxidants have increased exponentially, as have the number of articles written about those nutraceuticals. It seems like every time we open our emails there’s a new antioxidant super fruit being touted the best or most powerful antioxidant. My personal response to these emails is, “So what?” Even if a new super fruit/nutraceutical is a powerful antioxidant, what effects has it been shown to have in human beings? In other words, what specific benefits does the antioxidant offer, and to what parts of our bodies? This article will examine the role of some key antioxidants in relation to human health.
Free Radicals & Antioxidants 101
Before jumping into the individual antioxidants, let’s take a moment to review the relationship between free radicals and antioxidants. When cells use oxygen to generate energy, free radicals are created, including reactive oxygen species (ROS), reactive nitrogen species (RNS) and others. At high concentrations, they generate oxidative stress which can damage cell structures,1 which in turn may contribute to the development of leading degenerative diseases,2,3 as well as the process of aging itself. Conversely, antioxidants produced by the body or obtained from food/supplements act as free radical scavengers, preventing and repairing damages caused by ROS and RNS, thereby lowering the risk of degenerative diseases.4-8 In fact, specific antioxidants can have specific benefits with regard to disease prevention.
Alpha Lipoic Acid
In a four-week, placebo-controlled study, 72 type-2 diabetic patients received daily 600 mg, 1,200 mg or 1,800 mg of LA orally. The results were improved insulin sensitivity by 25 percent9 with no significant differences among the three doses of LA. This suggests that 600 mg daily day may be the maximum effective dose.10 Giving 600 mg to 1,200 mg oral or intravenous LA daily reduced symptoms of peripheral neuropathy in diabetics. LA improved symptoms such as burning, pain, numbness, and prickling of the feet and legs. It also seems to improve objective measures such as ratings of nerve function decline and disability. Symptom improvement occurs within three to five weeks with oral and intravenous dosing.11-19 Doses lower than 600 mg daily have not been shown to be effective.20
Astaxanthin
The cosmetic effects on human skin by 4 mg per day astaxanthin supplementation were demonstrated in a single blind placebo-controlled study21 using 49 U.S. healthy middle-aged women. Based upon dermatologist’s assessment and instrumental assessment at week 6 compared to base-line initial values, the results were more than a 50 percent reduction in fine lines and wrinkles, about a 50 percent improvement in the moisture content of skin, and more than a 50 percent improvement in skin elasticity. In addition, self-assessment of patients indicated a reduction of skin roughness by more than 40 percent.
Coenzyme Q10
Coenzyme Q10 (CoQ10) has been shown in multiple human studies to be effective in the prevention and treatment of various cardiovascular disorders.22 This includes angina and arrhythmias (abnormal heartbeat) in people who have had heart attacks,23,24 quality of life and various cardiac parameters in congestive heart failure,25-27 and a reduction in blood pressure in people with hypertension.28-31 These studies generally used at least 100 mg of CoQ10 daily.
Pyrroloquinoline Quinone (PQQ)
PQQ stimulates activity in mitochondria (those parts of cells than generate ATP, the energy “currency” of the body). In fact, PQQ has been shown to stimulate mitochondrial biogenesis (the production of new mitochondria) in animal research,32 increasing the number of mitochondria by 20-30 percent in PQQ supplemented mice compared to PQQ deficient mice.33 PQQ has also been show in human research34 to improve tests of higher cognitive function when combined with CoQ10. The dose of PQQ used in virtually all human studies is 20 mg daily.
Beta-carotene
In human research,35 30 mg/day of beta-carotene significantly improved facial wrinkles and elasticity in women. Likewise, there was a significant increase in procollagen gene expression, and decrease in UV damage—showing that beta-carotene supplementation daily prevented and repaired photo-aging of the skin.
Lycopene, Beta-carotene, Vitamin E and Selenium
In a study,36 the combination of 6 mg lycopene, 6 mg beta-carotene, 15 IU vitamin E, and 75 mcg selenium to reduce UV-induced damages in 25 healthy individuals exposed to UV irradiation. Researchers observed a significant 20 percent elevation of the “sunburn” threshold and a general reduction of UV-induced skin redness, a significant reduction of sunburn cells and significant parallel reduction of lipoperoxide levels (i.e. free radicals).37 Another study using the same combination of antioxidants as described above, but with 4.8 mg beta-carotene instead of 6, demonstrated a statistically significant increase in skin density (7 percent) and thickness (15 percent) after six and 12 weeks in the antioxidant group. Increases in skin density and thickness are measures of younger-looking skin. Likewise, there was a statistically significant decrease in skin scaling and roughness after 12 weeks.
Vitamin C, Beta-carotene, Vitamin E, Selenium and Zinc
A study38 with 4,447 participants (aged 45-60), examined the effects of daily supplementation with 120 mg vitamin C, 6 mg beta-carotene, 44.71 IU vitamin E, 100 mcg selenium, and 20 mg zinc. The results were better memory scores, including verbal memory (only in subjects who were nonsmokers or who had low serum vitamin C concentrations at baseline) and executive functioning.
Grapeseed Extract
Studies have shown that a specific water extract of grapeseed (MegaNatural BP) effectively reduced blood pressure in hypertensive individuals with 300 mg/day,39,40 as well as reducing the oxidation of LDL-cholesterol. Other research41,42 has shown that 150-300 mg/day of OPC from grape seed extract significantly reduced symptoms of venous insufficiency. In addition, 150 mg of OPC/day was shown to improve venous tone in people with widespread varicose veins. In addition, 133-400 mg OPC/day from grape seed extract was shown to be effective in reducing edema (i.e. water retention) in surgical patients,43 and people who regularly suffered from leg swelling in their work environments (due to prolonged sitting).44 An unrelated but interesting benefit is that 100 mg of grape seed extract before each meal reduced calorie intake by 4 percent in people who consumed 1,791 or more calories daily.45
Lutein and Zeaxanthin
Lutein and zeaxanthin play a role in healthy visual development and functioning, including the ability to efficiently absorb blue light.46 This function reduces the amount of blue light that reaches the critical visual structures of the eye may protect them from light-induced oxidative damage.47 Lutein is a predominant carotenoid in the central macula region of the eye.48 Furthermore, epidemiological research49 found that people with the highest level of dietary lutein-zeaxanthin intake (about 2.5 mg/day in a diet consisting of approximately 2,000 kcal) were half as likely to develop cataracts as people with low lutein-zeaxanthin. Other research has shown similar results.50,51
Conclusion
Although there are many more nutraceuticals I could address in this article (but didn’t due to space limitations), the ones I presented here certainly demonstrate that specific antioxidants offer specific health benefits. Hopefully, this information will help in determining which antioxidants may have the greatest value for individual needs. VR
References:
1 Pham-Huy LA, He H, Pham-Huy C. Free Radicals, Antioxidants in Disease and Health. Int J Biomed Sci. Jun 2008;4(2):89–96.
2 Florence TM. The role of free radicals in disease. Aust N Z J Ophthalmol. 1995 Feb;23(1):3-7.
3 Pham-Huy LA, He H, Pham-Huy C. Free Radicals, Antioxidants in Disease and Health. Int J Biomed Sci. Jun 2008;4(2):89–96.
4 Valko M, Rhodes CJ, Moncol J, Izakovic M, et al. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Mini-review. Chem. Biol. Interact. 2006;160:1–40.
5 Valko M, Morris H, Cronin MTD. Metals, toxicity and oxidative stress. Curr. Med. Chem. 2005;12:1161–1208.
6 Parthasarathy S, Santanam N, Ramachandran S, Meilhac O. Oxidants and antioxidants in atherogenesis: an appraisal. J. Lipid Res. 1999;40:2143–2157.
7 Frei B. Reactive oxygen species and antioxidant vitamins. Linus Pauling Institute. Oregon State University. 1997 http://lpi.oregonstate.edu/f-w97/reactive.html.
8 Chatterjee M, Saluja R, Kanneganti S, et al. Biochemical and molecular evaluation of neutrophil NOS in spontaneously hypertensive rats. Cell Mol. Biol. 2007;53:84–93.
9 Jacob S, Rett K, Henriksen EJ, Haring HU. Thioctic acid--effects on insulin sensitivity and glucose-metabolism. Biofactors. 1999;10(2-3):169-174.
10 Ziegler D. Thioctic acid for patients with symptomatic diabetic polyneuropathy: a critical review. Treat Endocrinol. 2004;3(3):173-189.
11 Ziegler D, Hanefeld M, Ruhnau K, et al. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: A 7-month, multicenter, randomized, controlled trial (ALADIN III Study). Diabetes Care 1999;22:1296-301.
12 Reljanovic M, Reichel G, Rett K, et al. Treatment of diabetic polyneuropathy with the antioxidant thioctic acid (alpha-lipoic acid): A 2-year, multicenter, randomized, double-blind, placebo-controlled trial (ALADIN II). Alpha Lipoic Acid in Diabetic Neuropathy. Free Radic Res 1999;31:171-7.
13 Ziegler D, Hanefeld M, Ruhnau KJ, et al. Treatment of symptomatic diabetic peripheral neuropathy with the antioxidant alpha-lipoic acid: A 3-week, multicenter, randomized, controlled trial (ALADIN Study). Diabetologia 1995;38:1425-33.
14 Ruhnau KJ, Meissner HP, Finn JR, et al. Effects of 3-week oral treatment with the antioxidant thioctic acid (alpha-lipoic acid) in symptomatic diabetic polyneuropathy. Diabet Med 1999;16:1040-3.
15 Ametov AS, Barinov A, Dyck PJ, et al. The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid. Diabetes Care 2003;26:770-6.
16 Ziegler D, Nowak H, Kemplert P, et al. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: A meta-analysis. Diabet Med 2004;21:114-21.
17 Negrisanu G, Rosu M, Bolte B, Lefter D, Dabelea D. Effects of 3-month treatment with the antioxidant alpha-lipoic acid in diabetic peripheral neuropathy. Rom J Intern Med 1999;37:297-306.
18 Zeigler D, Schatz H, Conrad F, Gries FA, Ulrich H, Reichel G. Effects of treatment with the antioxidant alpha-lipoic acid on cardiac autonomic neuropathy in NIDDM patients. A 4-month randomized controlled multicenter trial (DEKAN Study). Deutsche Kardiale Autonome Neuropathie. Diabetes Care 1997;20:369-373.
19 Tankova T, Cherninkova S, Koev D. Treatment for diabetic mononeuropathy with alpha-lipoic acid. Int J Clin Pract 2005;59:645-650.
20 Sachse G, Willms B. Efficacy of thioctic acid in the therapy of peripheral diabetic neuropathy. Hormone Metab Res Suppl 1980;9:105-7.
21 Yamashita E. The Effects of a Dietary Supplement Containing Astaxanthin on Skin Condition. Carotenoid Science. 2006;10:91-95.
22 Greenberg S, Frishman WH, J Clin Pharmacol (1990) 30(7):596-608.
23 Greenberg S, Frishman WH, J Clin Pharmacol (1990) 30(7):596-608.
24 Singh RB, et al, Cardiovasc Drugs Ther (1998) 12(4):347-53.
25 Soja AM, Mortensen SA, Ugeskr Laeger (1997) 159(49):7302-8.
26 Munkholm H, Hansen HH, Rasmussen K, Biofactors (1999) 9(2-4):285-9.
27 Sinatra ST, Conn Med (1997) 61(11):707-11.
28 Folkers K, et al, Res Commun Chem Pathol Pharmacol (1981) 31:129–40.
29 Langsjoen P, et al, Mol Aspects Med (1994) 15(Suppl):S265–72.
30 Digiesi V, et al, Molec Aspects Med (1994) 15(Suppl):S257–63.
31 Digiesi V, Cantini F, Brodbeck B, Curr Ther Res (1990) 47:841–45.
32 Chowanadisai W, Bauerly KA, Tchaparian E, Wong A, Cortopassi GA, Rucker RB. Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression. J Biol Chem. 2010 Jan 1;285(1):142-52.
33 Stites T, Storms D, Bauerly K, et al. Pyrroloquinoline quinone modulates mitochondrial quantity and function in mice. J Nutr. 2006 Feb;136(2):390-6.
34 http://pyrroloquinoline-quinone.com/pqq-info/ retrieved May 2, 2012.
35 Cho S, Lee DH, Won CH, Kim SM, Lee S, Lee MJ, Chung JH. Differential effects of low-dose and high-dose beta-carotene supplementation on the signs of photoaging and type I procollagen gene expression in human skin in vivo. Dermatology. 2010;221(2):160-71.
36 Césarini JP, Michel L, Maurette JM, Adhoute H, Béjot M. Immediate effects of UV radiation on the skin: modification by an antioxidant complex containing carotenoids. Photodermatol Photoimmunol Photomed 2003;19(4):182-9.
37 Heinrich U, Tronnier H, Stahl W, Béjot M, Maurette JM. Antioxidant supplements improve parameters related to skin structure in humans. Skin Pharmacol Physiol 2006;19(4):224-31.
38 Kesse-Guyot E, Fezeu L, Jeandel C, Ferry M, Andreeva V, Amieva H, Hercberg S, Galan P. French adults’ cognitive performance after daily supplementation with antioxidant vitamins and minerals at nutritional doses: a post hoc analysis of the Supplementation in Vitamins and Mineral Antioxidants (SU.VI.MAX) trial. Am J Clin Nutr 2011;94:892–9.
39 Sivaprakasapillai B, Edirisinghe I, Randolph J, Steinberg F, Kappagoda T. Effect of grape seed extract on blood pressure in subjects with the metabolic syndrome. Metabolism. 2009 Dec;58(12):1743-6.
40 Robinson M, Lu B, Kappagoda T. Effects of Grape Seed Extract in Subjects with Pre-Hypertension. Recent Advances in Cardiovascular Disease. 13th World Congress on Heart Disease. Vancouver, B.C., Canada, July 28-31, 2007: 239-242.
41 Thebaut JF, Thebaut P, Vin F. Study of Endotelon in functional manifestations of peripheral venous insufficiency. Gaz Med France 1985;92:96-100.
42 Delacrois P. Double-blind study of Endotelon in chronic venous insufficiency. La Revue De Med 1981;27:28
43 Pecking A, Desprez-Curely JP, Megret G. OPC (Endotelon) in the treatment of post-therapy lymphedemas of the upper extremities. Int’l d’Antiologie, Toulouse, France, Oct 4-7, 1989;69-73.
44 Sano A, Tokutake S, Seo A. Proanthocyanidin-rich grape seed extract reduces leg swelling in healthy women during prolonged sitting. J Sci Food Agric. 2013 Feb;93(3):457-62.
45 Vogels N, Nijs IM, Westerterp-Plantenga MS. The effect of grape-seed extract on 24 h energy intake in humans. Eur J Clin Nutr. 2004 Apr;58(4):667-73.
46 Halliwell B, Gutteridge JMC. Free Radicals in Biology and Medicine. Third ed. New York, NY: Oxford University Press; 1999. 47 Krinsky NI, Landrum JT, Bone RA. Biologic mechanisms of the protective role of lutein and zeaxanthin in the eye. Annu Rev Nutr. 2003;23:171-201.
48 Bone RA, Landrum JT, Fernandez L, Tarsis SL. Analysis of the macular pigment by HPLC: retinal distribution and age study. Invest Ophthalmol Vis Sci. 1988;29:843-849.
49 Lyle BJ, Mares-Perlman JA, Klein BE, Klein R, Greger JL. Antioxidant intake and risk of incident age-related nuclear cataracts in the Beaver Dam Eye Study. Am J Epidemiol. 1999 May 1;149(9):801-9.
50 Brown L, Rimm EB, Seddon JM, Giovannucci EL, Chasan-Taber L, Spiegelman D, Willett WC, Hankinson SE. A prospective study of carotenoid intake and risk of cataract extraction in US men. Am J Clin Nutr. 1999 Oct;70(4):517-24.
51 Chasan-Taber L, Willett WC, Seddon JM, Stampfer MJ, Rosner B, Colditz GA, Speizer FE, Hankinson SE. A prospective study of carotenoid and vitamin A intakes and risk of cataract extraction in US women. Am J Clin Nutr. 1999 Oct;70(4):509-16.
Gene Bruno, MS, MHS, the dean of academics for Huntington College of Health Sciences, is a nutritionist, herbalist, writer and educator. For more than 30 years he has educated and trained natural product retailers and health care professionals, has researched and formulated natural products for dozens of dietary supplement companies, and has written articles on nutrition, herbal medicine, nutraceuticals and integrative health issues for trade, consumer magazines and peer-reviewed publications.
The term antioxidant has become a mainstay in the lexicon of the natural products industry. Furthermore, as I pointed out in an article last year from this same issue of Vitamin Retailer magazine, over the past few decades the choices for nutraceutical antioxidants have increased exponentially, as have the number of articles written about those nutraceuticals. It seems like every time we open our emails there’s a new antioxidant super fruit being touted the best or most powerful antioxidant. My personal response to these emails is, “So what?” Even if a new super fruit/nutraceutical is a powerful antioxidant, what effects has it been shown to have in human beings? In other words, what specific benefits does the antioxidant offer, and to what parts of our bodies? This article will examine the role of some key antioxidants in relation to human health.
Free Radicals & Antioxidants 101
Before jumping into the individual antioxidants, let’s take a moment to review the relationship between free radicals and antioxidants. When cells use oxygen to generate energy, free radicals are created, including reactive oxygen species (ROS), reactive nitrogen species (RNS) and others. At high concentrations, they generate oxidative stress which can damage cell structures,1 which in turn may contribute to the development of leading degenerative diseases,2,3 as well as the process of aging itself. Conversely, antioxidants produced by the body or obtained from food/supplements act as free radical scavengers, preventing and repairing damages caused by ROS and RNS, thereby lowering the risk of degenerative diseases.4-8 In fact, specific antioxidants can have specific benefits with regard to disease prevention.
Alpha Lipoic Acid
In a four-week, placebo-controlled study, 72 type-2 diabetic patients received daily 600 mg, 1,200 mg or 1,800 mg of LA orally. The results were improved insulin sensitivity by 25 percent9 with no significant differences among the three doses of LA. This suggests that 600 mg daily day may be the maximum effective dose.10 Giving 600 mg to 1,200 mg oral or intravenous LA daily reduced symptoms of peripheral neuropathy in diabetics. LA improved symptoms such as burning, pain, numbness, and prickling of the feet and legs. It also seems to improve objective measures such as ratings of nerve function decline and disability. Symptom improvement occurs within three to five weeks with oral and intravenous dosing.11-19 Doses lower than 600 mg daily have not been shown to be effective.20
Astaxanthin
The cosmetic effects on human skin by 4 mg per day astaxanthin supplementation were demonstrated in a single blind placebo-controlled study21 using 49 U.S. healthy middle-aged women. Based upon dermatologist’s assessment and instrumental assessment at week 6 compared to base-line initial values, the results were more than a 50 percent reduction in fine lines and wrinkles, about a 50 percent improvement in the moisture content of skin, and more than a 50 percent improvement in skin elasticity. In addition, self-assessment of patients indicated a reduction of skin roughness by more than 40 percent.
Coenzyme Q10
Coenzyme Q10 (CoQ10) has been shown in multiple human studies to be effective in the prevention and treatment of various cardiovascular disorders.22 This includes angina and arrhythmias (abnormal heartbeat) in people who have had heart attacks,23,24 quality of life and various cardiac parameters in congestive heart failure,25-27 and a reduction in blood pressure in people with hypertension.28-31 These studies generally used at least 100 mg of CoQ10 daily.
Pyrroloquinoline Quinone (PQQ)
PQQ stimulates activity in mitochondria (those parts of cells than generate ATP, the energy “currency” of the body). In fact, PQQ has been shown to stimulate mitochondrial biogenesis (the production of new mitochondria) in animal research,32 increasing the number of mitochondria by 20-30 percent in PQQ supplemented mice compared to PQQ deficient mice.33 PQQ has also been show in human research34 to improve tests of higher cognitive function when combined with CoQ10. The dose of PQQ used in virtually all human studies is 20 mg daily.
Beta-carotene
In human research,35 30 mg/day of beta-carotene significantly improved facial wrinkles and elasticity in women. Likewise, there was a significant increase in procollagen gene expression, and decrease in UV damage—showing that beta-carotene supplementation daily prevented and repaired photo-aging of the skin.
Lycopene, Beta-carotene, Vitamin E and Selenium
In a study,36 the combination of 6 mg lycopene, 6 mg beta-carotene, 15 IU vitamin E, and 75 mcg selenium to reduce UV-induced damages in 25 healthy individuals exposed to UV irradiation. Researchers observed a significant 20 percent elevation of the “sunburn” threshold and a general reduction of UV-induced skin redness, a significant reduction of sunburn cells and significant parallel reduction of lipoperoxide levels (i.e. free radicals).37 Another study using the same combination of antioxidants as described above, but with 4.8 mg beta-carotene instead of 6, demonstrated a statistically significant increase in skin density (7 percent) and thickness (15 percent) after six and 12 weeks in the antioxidant group. Increases in skin density and thickness are measures of younger-looking skin. Likewise, there was a statistically significant decrease in skin scaling and roughness after 12 weeks.
Vitamin C, Beta-carotene, Vitamin E, Selenium and Zinc
A study38 with 4,447 participants (aged 45-60), examined the effects of daily supplementation with 120 mg vitamin C, 6 mg beta-carotene, 44.71 IU vitamin E, 100 mcg selenium, and 20 mg zinc. The results were better memory scores, including verbal memory (only in subjects who were nonsmokers or who had low serum vitamin C concentrations at baseline) and executive functioning.
Grapeseed Extract
Studies have shown that a specific water extract of grapeseed (MegaNatural BP) effectively reduced blood pressure in hypertensive individuals with 300 mg/day,39,40 as well as reducing the oxidation of LDL-cholesterol. Other research41,42 has shown that 150-300 mg/day of OPC from grape seed extract significantly reduced symptoms of venous insufficiency. In addition, 150 mg of OPC/day was shown to improve venous tone in people with widespread varicose veins. In addition, 133-400 mg OPC/day from grape seed extract was shown to be effective in reducing edema (i.e. water retention) in surgical patients,43 and people who regularly suffered from leg swelling in their work environments (due to prolonged sitting).44 An unrelated but interesting benefit is that 100 mg of grape seed extract before each meal reduced calorie intake by 4 percent in people who consumed 1,791 or more calories daily.45
Lutein and Zeaxanthin
Lutein and zeaxanthin play a role in healthy visual development and functioning, including the ability to efficiently absorb blue light.46 This function reduces the amount of blue light that reaches the critical visual structures of the eye may protect them from light-induced oxidative damage.47 Lutein is a predominant carotenoid in the central macula region of the eye.48 Furthermore, epidemiological research49 found that people with the highest level of dietary lutein-zeaxanthin intake (about 2.5 mg/day in a diet consisting of approximately 2,000 kcal) were half as likely to develop cataracts as people with low lutein-zeaxanthin. Other research has shown similar results.50,51
Conclusion
Although there are many more nutraceuticals I could address in this article (but didn’t due to space limitations), the ones I presented here certainly demonstrate that specific antioxidants offer specific health benefits. Hopefully, this information will help in determining which antioxidants may have the greatest value for individual needs. VR
References:
1 Pham-Huy LA, He H, Pham-Huy C. Free Radicals, Antioxidants in Disease and Health. Int J Biomed Sci. Jun 2008;4(2):89–96.
2 Florence TM. The role of free radicals in disease. Aust N Z J Ophthalmol. 1995 Feb;23(1):3-7.
3 Pham-Huy LA, He H, Pham-Huy C. Free Radicals, Antioxidants in Disease and Health. Int J Biomed Sci. Jun 2008;4(2):89–96.
4 Valko M, Rhodes CJ, Moncol J, Izakovic M, et al. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Mini-review. Chem. Biol. Interact. 2006;160:1–40.
5 Valko M, Morris H, Cronin MTD. Metals, toxicity and oxidative stress. Curr. Med. Chem. 2005;12:1161–1208.
6 Parthasarathy S, Santanam N, Ramachandran S, Meilhac O. Oxidants and antioxidants in atherogenesis: an appraisal. J. Lipid Res. 1999;40:2143–2157.
7 Frei B. Reactive oxygen species and antioxidant vitamins. Linus Pauling Institute. Oregon State University. 1997 http://lpi.oregonstate.edu/f-w97/reactive.html.
8 Chatterjee M, Saluja R, Kanneganti S, et al. Biochemical and molecular evaluation of neutrophil NOS in spontaneously hypertensive rats. Cell Mol. Biol. 2007;53:84–93.
9 Jacob S, Rett K, Henriksen EJ, Haring HU. Thioctic acid--effects on insulin sensitivity and glucose-metabolism. Biofactors. 1999;10(2-3):169-174.
10 Ziegler D. Thioctic acid for patients with symptomatic diabetic polyneuropathy: a critical review. Treat Endocrinol. 2004;3(3):173-189.
11 Ziegler D, Hanefeld M, Ruhnau K, et al. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: A 7-month, multicenter, randomized, controlled trial (ALADIN III Study). Diabetes Care 1999;22:1296-301.
12 Reljanovic M, Reichel G, Rett K, et al. Treatment of diabetic polyneuropathy with the antioxidant thioctic acid (alpha-lipoic acid): A 2-year, multicenter, randomized, double-blind, placebo-controlled trial (ALADIN II). Alpha Lipoic Acid in Diabetic Neuropathy. Free Radic Res 1999;31:171-7.
13 Ziegler D, Hanefeld M, Ruhnau KJ, et al. Treatment of symptomatic diabetic peripheral neuropathy with the antioxidant alpha-lipoic acid: A 3-week, multicenter, randomized, controlled trial (ALADIN Study). Diabetologia 1995;38:1425-33.
14 Ruhnau KJ, Meissner HP, Finn JR, et al. Effects of 3-week oral treatment with the antioxidant thioctic acid (alpha-lipoic acid) in symptomatic diabetic polyneuropathy. Diabet Med 1999;16:1040-3.
15 Ametov AS, Barinov A, Dyck PJ, et al. The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid. Diabetes Care 2003;26:770-6.
16 Ziegler D, Nowak H, Kemplert P, et al. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: A meta-analysis. Diabet Med 2004;21:114-21.
17 Negrisanu G, Rosu M, Bolte B, Lefter D, Dabelea D. Effects of 3-month treatment with the antioxidant alpha-lipoic acid in diabetic peripheral neuropathy. Rom J Intern Med 1999;37:297-306.
18 Zeigler D, Schatz H, Conrad F, Gries FA, Ulrich H, Reichel G. Effects of treatment with the antioxidant alpha-lipoic acid on cardiac autonomic neuropathy in NIDDM patients. A 4-month randomized controlled multicenter trial (DEKAN Study). Deutsche Kardiale Autonome Neuropathie. Diabetes Care 1997;20:369-373.
19 Tankova T, Cherninkova S, Koev D. Treatment for diabetic mononeuropathy with alpha-lipoic acid. Int J Clin Pract 2005;59:645-650.
20 Sachse G, Willms B. Efficacy of thioctic acid in the therapy of peripheral diabetic neuropathy. Hormone Metab Res Suppl 1980;9:105-7.
21 Yamashita E. The Effects of a Dietary Supplement Containing Astaxanthin on Skin Condition. Carotenoid Science. 2006;10:91-95.
22 Greenberg S, Frishman WH, J Clin Pharmacol (1990) 30(7):596-608.
23 Greenberg S, Frishman WH, J Clin Pharmacol (1990) 30(7):596-608.
24 Singh RB, et al, Cardiovasc Drugs Ther (1998) 12(4):347-53.
25 Soja AM, Mortensen SA, Ugeskr Laeger (1997) 159(49):7302-8.
26 Munkholm H, Hansen HH, Rasmussen K, Biofactors (1999) 9(2-4):285-9.
27 Sinatra ST, Conn Med (1997) 61(11):707-11.
28 Folkers K, et al, Res Commun Chem Pathol Pharmacol (1981) 31:129–40.
29 Langsjoen P, et al, Mol Aspects Med (1994) 15(Suppl):S265–72.
30 Digiesi V, et al, Molec Aspects Med (1994) 15(Suppl):S257–63.
31 Digiesi V, Cantini F, Brodbeck B, Curr Ther Res (1990) 47:841–45.
32 Chowanadisai W, Bauerly KA, Tchaparian E, Wong A, Cortopassi GA, Rucker RB. Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression. J Biol Chem. 2010 Jan 1;285(1):142-52.
33 Stites T, Storms D, Bauerly K, et al. Pyrroloquinoline quinone modulates mitochondrial quantity and function in mice. J Nutr. 2006 Feb;136(2):390-6.
34 http://pyrroloquinoline-quinone.com/pqq-info/ retrieved May 2, 2012.
35 Cho S, Lee DH, Won CH, Kim SM, Lee S, Lee MJ, Chung JH. Differential effects of low-dose and high-dose beta-carotene supplementation on the signs of photoaging and type I procollagen gene expression in human skin in vivo. Dermatology. 2010;221(2):160-71.
36 Césarini JP, Michel L, Maurette JM, Adhoute H, Béjot M. Immediate effects of UV radiation on the skin: modification by an antioxidant complex containing carotenoids. Photodermatol Photoimmunol Photomed 2003;19(4):182-9.
37 Heinrich U, Tronnier H, Stahl W, Béjot M, Maurette JM. Antioxidant supplements improve parameters related to skin structure in humans. Skin Pharmacol Physiol 2006;19(4):224-31.
38 Kesse-Guyot E, Fezeu L, Jeandel C, Ferry M, Andreeva V, Amieva H, Hercberg S, Galan P. French adults’ cognitive performance after daily supplementation with antioxidant vitamins and minerals at nutritional doses: a post hoc analysis of the Supplementation in Vitamins and Mineral Antioxidants (SU.VI.MAX) trial. Am J Clin Nutr 2011;94:892–9.
39 Sivaprakasapillai B, Edirisinghe I, Randolph J, Steinberg F, Kappagoda T. Effect of grape seed extract on blood pressure in subjects with the metabolic syndrome. Metabolism. 2009 Dec;58(12):1743-6.
40 Robinson M, Lu B, Kappagoda T. Effects of Grape Seed Extract in Subjects with Pre-Hypertension. Recent Advances in Cardiovascular Disease. 13th World Congress on Heart Disease. Vancouver, B.C., Canada, July 28-31, 2007: 239-242.
41 Thebaut JF, Thebaut P, Vin F. Study of Endotelon in functional manifestations of peripheral venous insufficiency. Gaz Med France 1985;92:96-100.
42 Delacrois P. Double-blind study of Endotelon in chronic venous insufficiency. La Revue De Med 1981;27:28
43 Pecking A, Desprez-Curely JP, Megret G. OPC (Endotelon) in the treatment of post-therapy lymphedemas of the upper extremities. Int’l d’Antiologie, Toulouse, France, Oct 4-7, 1989;69-73.
44 Sano A, Tokutake S, Seo A. Proanthocyanidin-rich grape seed extract reduces leg swelling in healthy women during prolonged sitting. J Sci Food Agric. 2013 Feb;93(3):457-62.
45 Vogels N, Nijs IM, Westerterp-Plantenga MS. The effect of grape-seed extract on 24 h energy intake in humans. Eur J Clin Nutr. 2004 Apr;58(4):667-73.
46 Halliwell B, Gutteridge JMC. Free Radicals in Biology and Medicine. Third ed. New York, NY: Oxford University Press; 1999. 47 Krinsky NI, Landrum JT, Bone RA. Biologic mechanisms of the protective role of lutein and zeaxanthin in the eye. Annu Rev Nutr. 2003;23:171-201.
48 Bone RA, Landrum JT, Fernandez L, Tarsis SL. Analysis of the macular pigment by HPLC: retinal distribution and age study. Invest Ophthalmol Vis Sci. 1988;29:843-849.
49 Lyle BJ, Mares-Perlman JA, Klein BE, Klein R, Greger JL. Antioxidant intake and risk of incident age-related nuclear cataracts in the Beaver Dam Eye Study. Am J Epidemiol. 1999 May 1;149(9):801-9.
50 Brown L, Rimm EB, Seddon JM, Giovannucci EL, Chasan-Taber L, Spiegelman D, Willett WC, Hankinson SE. A prospective study of carotenoid intake and risk of cataract extraction in US men. Am J Clin Nutr. 1999 Oct;70(4):517-24.
51 Chasan-Taber L, Willett WC, Seddon JM, Stampfer MJ, Rosner B, Colditz GA, Speizer FE, Hankinson SE. A prospective study of carotenoid and vitamin A intakes and risk of cataract extraction in US women. Am J Clin Nutr. 1999 Oct;70(4):509-16.
Gene Bruno, MS, MHS, the dean of academics for Huntington College of Health Sciences, is a nutritionist, herbalist, writer and educator. For more than 30 years he has educated and trained natural product retailers and health care professionals, has researched and formulated natural products for dozens of dietary supplement companies, and has written articles on nutrition, herbal medicine, nutraceuticals and integrative health issues for trade, consumer magazines and peer-reviewed publications.
Follow Us