Grape seed

Overview

Grape seed extract is mostly used for its antioxidant qualities and for its numerous cardioprotective and circulatory benefits. Recently grape seed extract attained GRAS status with the FDA and due to this it is expected to become more popular in functional foods. The active constituents of grape seed extract are proanthocyanidins, the procyanidin oligomers (PCOs). Grape seed or PCO extracts normally contain a mixture of PCOs of different lengths (dimers, trimers, tetramers and oligomers of up to 7 units).

Grape seed extract has been confirmed in both preclinical and clinical studies to be a potent antioxidant, and it has good clinical evidence of its usefulness in preventing and ameliorating cardiovascular and circulatory disorders. Grape seed extract and the PCOs from grape seed have been studied in animals and in vitro to confirm the cardioprotective, circulatory and antioxidant benefits found from traditional use. Some of the key preclinical studies are listed below:

•Rabbits fed grape-seed extracts in cholesterol-enriched diets showed significant decrease in cholesteryl ester hydroperoxides compared to the controls fed cholesterol-enriched diets alone. The rabbits in the grape seed extract group also showed significantly fewer atherosclerotic plaques in their aortic arch, a significant decrease in the total cholesterol and malondialdehyde (MDA) contents in the aortic arch and thoracic aorta, and a decrease in the number of foam cells in oxidized low-density lipoprotein (LDL)-positive cells of the atherosclerotic lesions (Yamakoshi et al., 1999).

•The cardioprotective effects of PCOs were found to be mediated by: a) scavenging of oxygen-centered radicals (hydroxyl and peroxyl); and b) sequestration of the cations Fe+2 and Cu+2, which enhance the formation of harmful hydroxyl radicals when triggered by superoxide/hydrogen peroxide (Maffei Facinó et al., 1996).

•The cardioprotective benefits of grape seed extract was shown in rats. Compared to controls, the rats fed the grape seed extract showed a significantly faster recovery time from myocardial infarction, significantly smaller infarct mass and size and higher aortic flow (Sato et al, 1999).

•Jonadet et al. (1983) found that grape seed showed the highest in vitro elastase-inhibiting activities compared to bilberry and pine park. Elastase is involved with the destruction of elastic fibers and conjunctive tissue.

•Procyanidins from grape seed are known to inhibit lipid peroxidation because they are effective scavengers of superoxide anion, hydroxyl radical anion, and lipid peroxyl radicals (Maffei Facinó et al., 1996; Meunier et al., 1989).

•Procyanidins also indirectly have antioxidant functions by inhibiting oxidation of low-density lipoprotein (LDL) catalyzed by Cu+2 (Frankel et al., 1993).

Comments

Grape seed is a good example of a non-toxic (GRAS) botanical that has several benefits in supplementing the diet. It has been confirmed use as an antioxidant as a cardioprotective and for circulatory health, and would make an excellent daily addition to the standard American diet.

Scientific Support

Peripheral Vascular Benefits

Retinopathies were studied by a) a controlled study of 75 patients with ocular stress caused by a visual display unit, and b) another study of 91 myopic patients. Procyanidins (300 mg/day for 60 days) caused significant improvement of subjective symptoms and contrast sensitivity relative to the control group in study a). In the second study b) retinal function was reported to have improved from administration of 300 mg/day of procyanidins for 28 days (Bombardelli and Morazzoni, 1995).

A double-blind, placebo-controlled study of 92 patients with peripheral venous insufficiency found procyanidins (300 mg daily for 28 days) effective in 75% of the patients. Procyanidin treatment was found to improve the functional measures (pain, paresthesias, nocturnal cramps, edema, etc) of venous insufficiency by more than 50% (Bombardelli and Morazzoni, 1995).

Visual adaptation to low intensity light (night morphoscopic vision) and visual performance following glare was improved in patients given a grape seed extract (Endotelon®, 200 mg per day for 5 weeks). The study was placebo controlled and utilized 100 subjects without ophthalmological pathology (Corbe et al., 1988).

Lesbre and Tigaude (1983) conducted a randomized, placebo-controlled study in 20 patients diagnosed with capillary hyperpermeability and hepatic cirrhosis. The capillary fragility index in the patients given the grape seed extract (150 mg proanthocyanidins, two times a day for eight weeks) was significantly higher than placebo.

Sarrat (1981) conducted a study on 30 patients without varicose veins for the effect of grape seed extract (150 mg/30 days), diosamine (a semi-synthetic flavonoid product), or placebo on the possible indications that could develop into varicose veins later in life. The grape seed extract significantly lowered the occurrence of indications such as heaviness of the legs, cramps, itching, abnomal sensations such as burning and prickling and the sensation of swelling. The author concluded that grape seed extract might be effective in preventing varicose veins from developing.

In a double-blind study, grape seed extract (Endotelon®, 150 mg daily for 30 days) was compared against diosamine (450 mg/day for 30 days) for its effect on 50 female patients with chronic venous insufficiency (mostly pregnancy-related). Although both treatments were effective in reducing the symptoms of chronic venous insufficiency, grape seed extract showed a faster action that also lasted longer. Also, only 45% of the diosamine group became symptom-free compared to 65% of the grape seed extract group (Delacroix, 1981).

Royer and Schmidt (1981) showed in an preliminary study that a single oral dose of procyanidins increased objectively the venous tone in patients with widespread varicose veins.

The effect of procyanidins (150 mg/day) in 25 diabetic and hypertensive patients in a double-blind, placebo controlled study was investigated. Capillary resistance increased 23% in the treatment group. In another study of 28 diabetic and hypertensive patients, capillary resistance was found to increase 18% using a similar dose of procyanidins (Lagrue et al., 1981).

Dartenuc et al. (1980) conducted a double-blind study with standardized grape seed extract in 37 hospitalized patients with capillary fragility. Endotelon® was administered at the rate of 50 mg of proanthocyanidins two times daily over 15 days. In 10 out of 21 of the patients given the extract, and in 3 out of 12 on placebo, capillary resistance was improved.

A double-blind, placebo-controlled study of a standardized grape seed extract on 71 patients with peripheral venous insufficiency found grape seed extract to have a significant beneficial effect. Grape seed extract treatment (Endotelon®, 100 mg three times daily for 28 days) caused significant improvement in symptoms of nocturnal cramps, leg heaviness, edema and tingling. Improvements were found for 75% of the active treatment group compared to 41% on placebo) (Thébaut et al., 1978).

Visual acuity was improved or remained stable in 29 out of 30 patients diagnosed with atherosclerotic retinopathy. In this double-blind, placebo-controlled study, the patients were given 100 mg daily of proanthocyanidins for one year or placebo (Verin et al., 1978).

Antioxidant Activity

The antioxidant activity of grape seed extract (300 mg/day for 5 days of a standardized extract with 150 mg of grape procyanidins/capsule) was studied in 20 healthy, nonsmoking adults who all followed a standardized dietary pattern in a single-blinded, randomized, placebo-controlled crossover study. The mean total antioxidant capacity (TAC) of the serum of the treatment group was significantly improved compared to baseline, and showed no significant change in the placebo group (Nuttall et al., 1998).

Safety / Dosage

The dosage recommendation of grape seed extract (containing 80-85% procyanidin oligomers) depends on whether the treatment is for preventative or therapeutic purposes. For prevention, 50 mg is recommended (or 125 mg of a bound form such as PCO-phosphatdylecholine). For therapeutic purposes, the dosage should range between 150 and 30 mg. Procyanidins have been found to have a synergistic effect with Vitamin C (McKenna et al., 2001).

Mild and transient side effects have been found during clinical trials, including mild gastrointestinal discomfort, vertigo, nausea, allergic reactions and headaches. Some PCOs can produce a platelet antiaggretory activity, and therefore would be contraindicated for those on anticoagulant medications, for those about to enter surgery (McKenna et al., 2001).

Procyanidins are thought to be safe during pregnancy, as no teratenogenic effects were found in pregnant chicks, mice, or rabbits at doses ten times the normal, and no contraindications were found from clinical studies in humans. There is no safety data available on grape seed extract use during lactation (McKenna et al., 2001).

References

1.Bombardelli E, Morazzoni P. Vitis vinifera L. Fitoterapia 1995; 66:291-317.

2.Corbe C, Boissin JP, Siou A. Light vision and chorioretinal circulation. Study of the effect of procyanidolic oligomers (Endotelon). J Fr Ophtalmol. 1988;11(5):453-60.

3.Dartenuc JY, Marache P, Choussat H. Capillary resistance in geriatrics. A study of a microangioprotector = Endotelon. Bordeaux Médical 1980; 13:903-907.

4.Delacroix, P. Double-blind trial of Endotelon in chronic venous insufficiency. La Revue de Médecine 1981; (27-28):1793-1802.

5.Frankel EN, Kanner J, German JB, Parks E, Kinsella JE. Inhibition of oxidation of human low-density lipoprotein by phenolic substances in red wine. Lancet. 1993 Feb 20;341(8843):454-7.

6.Jonadet M, Meunier MT, Bastide J, Bastide P. Anthocyanosides extracted from Vitis vinifera, Vaccinium myrtillus and Pinus maritimus. I. Elastase-inhibiting activities in vitro. II. Compared angioprotective activities in vivo. J Pharm Belg. 1983 Jan-Feb;38(1):41-6.

7.Lagrue G, Olivier-Martin F, Grillot A. A study of the effects of procyanidol oligomers on capillary resistance in hypertension and in certain nephropathies. Sem Hop. 1981 Sep 18-25;57(33-36):1399-401.

8.Lesbre FX, Tigaud, JD. The effect of Endotelon on the capillary fragility index of a specified controlled group: cirrhosis patients. Gazette Medicale 1983; 90:24-28.

9.McKenna DJ, Jones K, Hughes K (eds). Botanical Medicines: A Desktop Reference for the Major Herbal Supplements. Haworth Press: New York

10.Maffei Facino R, Carini M, Aldini G, Berti F, Rossoni G, Bombardelli E, Morazzoni P. Procyanidines from Vitis vinifera seeds protect rabbit heart from ischemia/reperfusion injury: antioxidant intervention and/or iron and copper sequestering ability. Planta Med. 1996 Dec;62(6):495-502.

11.Meunier MT, Duroux E, Bastide, P. Free-radical scavenging activity of procyanidolic oligomers and anthocyanosides with respect to superoxide anion and lipid peroxidation. Plantes Medicinales et Phytotherapie 1989; 23:267-274.

12.Nuttall SL, Kendall MJ, Bombardelli E, Morazzoni P. An evaluation of the antioxidant activity of a standardized grape seed extract, Leucoselect. J Clin Pharm Ther. 1998 Oct;23(5):385-9.

13.Royer RJ, Schmidt CL. Evaluation of venotropic drugs by venous gas plethysmography. A study of procyanidolic oligomers. Sem Hop. 1981 Dec 18-25;57(47-48):2009-13.

14.Sato M, Maulik G, Ray PS, Bagchi D, Das DK Cardioprotective effects of grape seed proanthocyanidin against ischemic reperfusion injury. J Mol Cell Cardiol. 1999 Jun;31(6):1289-97.

15.Thébaut JF, Thébaut P, Vin F. Study of Endotelon in functional manifesations of peripheral venous insufficiency. Results of one double-blind carried out on 92 patients. Gazette Médicale 1985; 92:96-100.

16.Vérin MMP, Vildy A, Maurin JF. Retinopathies and O.P.C. Bordeaux Médical 1978; 11:1467-1474.

17.Yamakoshi J, Kataoka S, Koga T, Ariga T. Proanthocyanidin-rich extract from grape seeds attenuates the development of aortic atherosclerosis in cholesterol-fed rabbits. Atherosclerosis. 1999 Jan;142(1):139-49.

EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.

Green Tea

Overview

Green tea (Camellia sinensis) is the second-most consumed beverage in the world (water is the first) and has been used medicinally for centuries in India and China. A number of beneficial health effects are attributed to regular consumption of green tea and dried/powdered extracts of green tea are available as dietary supplements. Green tea is prepared by picking, lightly steaming the leaves, and allowing them to dry. Black tea, the most popular type of tea in the U.S., is made by allowing the leaves to ferment before drying. Due to differences in the fermentation process, a portion of the active compounds are destroyed in black tea, but remain active in green tea. The active constituents in green tea are a family of polyphenols (catechins) with potent antioxidant activity. Tannins, large polyphenol molecules, form the bulk of the active compounds in green tea, with catechins comprising nearly 90%. Several catechins are present in significant quantities; epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG) and epigallocatechin gallate (EGCG). EGCG makes up about 10-50% of the total catechin content and appears to be the most powerful of the catechins – with antioxidant activity about 25-100 times more potent than vitamins C and E. A cup of green tea may provide 10-40mg of polyphenols and has antioxidant activity greater than a serving of broccoli, spinach, carrots or strawberries. A number of commercial green tea extracts are standardized to total polyphenol content and/or EGCG content and many are marketed with claims for preventing cancer, enhancing immune function, boosting antioxidant protection, reducing cholesterol, and stimulating weight loss.

Comments

Green tea consumed either as a beverage or as a daily dietary supplement is especially beneficial for individuals at high risk for cancer (e.g. family history) or those undergoing or recovering from chemotherapy or radiation treatment. Green tea is also beneficial as a general protective measure and dietary “insurance” of adequate polyphenol intake (which would otherwise be obtained from a diet high in fruits and vegetables). Recent data provides strong evidence that green tea may be effective in stimulating thermogenesis, increasing caloric expenditure, promoting fat oxidation and controlling body weight.

Scientific Support

Because the active compounds, the catechins, found in green tea are known to possess potent antioxidant activity, they may provide beneficial health effects by protecting the body from the damaging effects of oxidative damage from free radicals. A number of chronic disease states have been associated with free radical induced oxidative damage, including cancer, heart disease, suppressed immune function and accelerated aging.

Although numerous laboratory investigations have shown the powerful antioxidant activity of green tea and green tea extracts (August et al. 1999, Benzie et al. 1999), prospective clinical studies in humans are few (Hakim et al. 2003, Hakim et al. 2004). From the laboratory findings, it is clear that green tea is an effective antioxidant, that it provides clear protection from experimentally induced DNA damage and that it can slow or halt the initiation and progression of cancerous tumor growth (Ahn et al. 2003). There is also evidence from some studies that green tea provides significant immunoprotective qualities, particularly in the case of cancer patients undergoing radiation or chemotherapy (Elmets et al. 2001, Pisters et al. 2001). White blood cell count appears to be maintained more effectively in cancer patients consuming green tea compared to non-supplemented patients.

Several epidemiological studies show an association between consumption of total flavonoids in the diet and the risk for cancer and heart disease. Men with the highest consumption of flavonoids (from fruits and vegetables) have approximately half the risk of heart disease and cancer compared to those with the lowest intake. The primary catechin in green tea, EGCG, appears to inhibit the growth of cancer cells as well as play a role in stimulating apoptosis (programmed cell death), both of which are crucial aspects for cancer prevention (Pisters et al. 2001, Weisburger et al. 1998).

In terms of heart disease protection, the potent antioxidant properties of polyphenols would be expected to reduce free radical damage to cells and prevent the oxidation of LDL cholesterol – both of which would be expected to inhibit the formation of atherosclerotic plaques (Hodgson et al. 2000).

Aside from the clear benefits of green tea as an antioxidant, recent studies have suggested a role of catechins in promoting weight loss. Animal studies have shown green tea (and oolong tea) to suppress food intake, body weight gain, and fat tissue accumulation, while human studies have shown increases in metabolic rate and better weight maintenance following weight loss (Komatsu et al. 2003, Kovacs et al. 2004).

In some studies, green tea is associated with a mild increase in thermogenesis (increased caloric expenditure) – which is generally attributed to its caffeine content. However, a handful of studies have shown that green tea extract stimulates thermogenesis to an extent much greater than can be attributed directly to its caffeine content alone – meaning that the thermogenic properties of green tea may be due to an interaction between caffeine and its high content of catechin-polyphenols (Chantre and Lairon et al. 2002, Dulloo et al. 1999). A probable theory for the thermogenic effect of green tea is an increase in levels of norepinephrine – because catechin-polyphenols are known to inhibit catechol-O-methyl-transferase (the enzyme that degrades norepinephrine). One study examined this theory, and the effect of green tea extract on 24-hour energy expenditure, in 10 healthy men – who each consumed 3 treatments of green tea extract (50mg caffeine and 90mg epigallocatechin gallate), caffeine (50 mg), and placebo at breakfast, lunch, and dinner (Dulloo et al. 1999). The results of the study showed that, relative to placebo, the green tea extract resulted in a significant (4%) increase in 24-hour energy expenditure (approximately 80 calories per day) and a significant increase in the body’s use of fat as an energy source (24-h respiratory quotient). In addition, the 24-hour urinary norepinephrine excretion was 40% higher during treatment with the green tea extract than with the placebo. It is interesting to note that treatment with caffeine in amounts equivalent to those found in the green tea extract (50mg) had no effect on energy expenditure or fat oxidation – suggesting that the thermogenic properties of green tea are due to compounds other than its caffeine content alone (Komatsu et al. 2003, Kovacs et al. 2004).

Because norepinephrine levels in humans are also associated with alertness, mental focus, attention, and overall mood – maintaining normal levels of this important neurotransmitter may have benefits for improving mood (reducing depression) and maintaining mental function (reducing attention deficit symptoms) through a mechanism of action similar to a number of pharmaceutical agents (Concerta, Strattera, Effexor).

Safety/Dosage

Green tea consumption of as much as 20 cups per day has not been associated with any significant side effects. In high doses, however, teas that contain caffeine may lead to restlessness, insomnia, heart palpitations and tachycardia (rapid heartbeat). Decaffeinated versions of green tea and green tea extracts are available – but due to differences in caffeine extraction methods, the amounts of phenolic/catechin compounds can vary between extracts. In addition, individuals taking aspirin or other anticoagulant agents (including vitamin E and ginkgo biloba) on a daily basis should be aware of the possible inhibition of platelet aggregation (blood clotting) associated with green tea (in some cases, green tea may prolong bleeding times). Typical dosage recommendations are for 100-500mg/day – preferably of an extract standardized to at least 40% polyphenols and/or EGCG as a marker compound (roughly equivalent to 4-10 cups of brewed green tea).

References

1.Ahn WS, Yoo J, Huh SW, Kim CK, Lee JM, Namkoong SE, Bae SM, Lee IP. Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions. Eur J Cancer Prev. 2003 Oct;12(5):383-90.

2.August DA, Landau J, Caputo D, Hong J, Lee MJ, Yang CS. Ingestion of green tea rapidly decreases prostaglandin E2 levels in rectal mucosa in humans. Cancer Epidemiol Biomarkers Prev. 1999 Aug;8(8):709-13.

3.Benzie IF, Szeto YT, Strain JJ, Tomlinson B. Consumption of green tea causes rapid increase in plasma antioxidant power in humans. Nutr Cancer. 1999;34(1):83-7.

4.Chantre P, Lairon D. Recent findings of green tea extract AR25 (Exolise) and its activity for the treatment of obesity. Phytomedicine. 2002 Jan;9(1):3-8.

5.Chow HH, Cai Y, Alberts DS, Hakim I, Dorr R, Shahi F, Crowell JA, Yang CS, Hara Y. Phase I pharmacokinetic study of tea polyphenols following single-dose administration of epigallocatechin gallate and polyphenon E. Cancer Epidemiol Biomarkers Prev. 2001 Jan;10(1):53-8.

6.Dulloo AG, Duret C, Rohrer D, Girardier L, Mensi N, Fathi M, Chantre P, Vandermander J. Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans. Am J Clin Nutr. 1999 Dec;70(6):1040-5.

7.Dulloo AG, Seydoux J, Girardier L, Chantre P, Vandermander J. Green tea and thermogenesis: interactions between catechin-polyphenols, caffeine and sympathetic activity. Int J Obes Relat Metab Disord. 2000 Feb;24(2):252-8.

8.Elmets CA, Singh D, Tubesing K, Matsui M, Katiyar S, Mukhtar H. Cutaneous photoprotection from ultraviolet injury by green tea polyphenols. J Am Acad Dermatol. 2001 Mar;44(3):425-32.

9.Gupta S, Ahmad N, Mohan RR, Husain MM, Mukhtar H. Prostate cancer chemoprevention by green tea: in vitro and in vivo inhibition of testosterone-mediated induction of ornithine decarboxylase. Cancer Res. 1999 May 1;59(9):2115-20.

10.Hakim IA, Harris RB, Brown S, Chow HH, Wiseman S, Agarwal S, Talbot W. Effect of increased tea consumption on oxidative DNA damage among smokers: a randomized controlled study. J Nutr. 2003 Oct;133(10):3303S-3309S.

11.Hakim IA, Harris RB, Chow HH, Dean M, Brown S, Ali IU. Effect of a 4-month tea intervention on oxidative DNA damage among heavy smokers: role of glutathione S-transferase genotypes. Cancer Epidemiol Biomarkers Prev. 2004 Feb;13(2):242-9.

12.Hodgson JM, Puddey IB, Croft KD, Burke V, Mori TA, Caccetta RA, Beilin LJ. Acute effects of ingestion of black and green tea on lipoprotein oxidation. Am J Clin Nutr. 2000 May;71(5):1103-7.

13.Komatsu T, Nakamori M, Komatsu K, Hosoda K, Okamura M, Toyama K, Ishikura Y, Sakai T, Kunii D, Yamamoto S. Oolong tea increases energy metabolism in Japanese females. J Med Invest. 2003 Aug;50(3-4):170-5.

14.Kovacs EM, Lejeune MP, Nijs I, Westerterp-Plantenga MS. Effects of green tea on weight maintenance after body-weight loss. Br J Nutr. 2004 Mar;91(3):431-7.

15.Lin JK, Liang YC, Lin-Shiau SY. Cancer chemoprevention by tea polyphenols through mitotic signal transduction blockade. Biochem Pharmacol. 1999 Sep 15;58(6):911-5.

16.Maron DJ, Lu GP, Cai NS, Wu ZG, Li YH, Chen H, Zhu JQ, Jin XJ, Wouters BC, Zhao J. Cholesterol-lowering effect of a theaflavin-enriched green tea extract: a randomized controlled trial. Arch Intern Med. 2003 Jun 23;163(12):1448-53.

17.Pisters KM, Newman RA, Coldman B, Shin DM, Khuri FR, Hong WK, Glisson BS, Lee JS. Phase I trial of oral green tea extract in adult patients with solid tumors. J Clin Oncol. 2001 Mar 15;19(6):1830-8.

18.Weisburger JH, Rivenson A, Aliaga C, Reinhardt J, Kelloff GJ, Boone CW, Steele VE, Balentine DA, Pittman B, Zang E. Effect of tea extracts, polyphenols, and epigallocatechin gallate on azoxymethane-induced colon cancer. Proc Soc Exp Biol Med. 1998 Jan;217(1):104-8.

EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.

Lutein & Zeaxanthin

Overview

Lutein and zeaxanthin are carotenoids found in highest concentrations in the macular region of the eyes (the back of the eye where the retina is located), where they are believed to help filter out damaging blue light and prevent free radical damage to the delicate structures in the back of the eye. Dietary supplements containing lutein and zeaxanthin are commonly recommended to help prevent age-related macular degeneration (ARMD) and the development of glaucoma and cataracts.

Because antioxidants can provide increased protection against the oxidizing ultraviolet radiation of the sun, anybody that spends time outdoors exposed to the sun should be concerned with the potential for ultraviolet radiation to damage eye health and impact vision. Lutein and zeaxanthin are the only carotenoids that become concentrated in the retinal region of the eye – known as the macula. High dietary intake of lutein-rich fruits and vegetables (yellow and dark green) has been associated with a significant reduction in macular degeneration – the leading cause of blindness in Americans over the age of 65.

Comments

Dietary supplements containing lutein and zeaxanthin are available from a number of manufacturers as an alternative for those people not able or willing to increase their consumption of brightly colored fruits and vegetables. When choosing a supplement, be sure to select one that delivers an effective level of lutein (about 4-6mg/day). Lutein is now being added to national brands of multi-vitamins – but most provide only 250 micrograms (mcg) or less of lutein – or more than 20 times less than the levels shown to be effective in preventing ARMD and even several times below levels that could reasonably be achieved in the diet from a high-intake of fruits and vegetables.

Scientific Support

Lutein and zeaxanthin are yellow pigments found in high concentrations in egg yolks, yellow fruits and vegetables as well as in dark green, leafy vegetables. In particular, spinach, kale and collard greens contain high levels of these two carotenoids – and numerous dietary survey studies (Castenmiller et al. 1999, Sommerburg et al. 1998) have shown that those individuals with the highest spinach consumption (a rich source of lutein) have the lowest risk of developing ARMD (reductions of as much as 90% in some cases).

Both lutein and zeaxanthin seem to reduce the risk of ARMD and protect overall eye health by at least two different routes. First, both of these carotenoids are absorbed from the diet into the circulation and eventually concentrate specifically in the eye (in the macular region of the retina). It is interesting to note that lutein and zeaxanthin are the only carotenoids known to concentrate specifically in the eye tissues. The high levels of these carotenoids in the eye serve to protect tissues by minimizing free radical damage and by absorbing damaging blue light rays (Landrum et al. 1997)).

It is thought that a low macular pigment density may increase the risk ARMD and cataracts by allowing more damage from blue light (Sommerburg et al. 1999). Several observational studies have shown that high dietary intakes of lutein and zeaxanthin (from spinach, broccoli and eggs) are associated with a significant 20% reduction in the risk for cataracts (Moeller et al. 2000) and approximately 40% for age-related macular degeneration (Bartlett and Esperjesi 2003, Mozaffarieth et al. 2003). Studies have shown that dietary supplementation with lutein (30mg/day for 140 days) elevates serum lutein levels by 10 times, increases macular pigment density by 20-40% and reduces transmission of blue light to the eye’s photoreceptors by 30-40% (Hammond et al. 1997, Johnson et al. 2000). Other studies have shown that daily egg yolk consumption can increase plasma levels of lutein by 28-50% and zeaxanthin by 114-142%. Multi-center clinical studies of patients with advanced ARMD (age range 55-80 years) have found the risk for ARMD to be reduced by over 40% by a high dietary intake of carotenoids (Pratt 1999). In particular, both lutein and zeaxanthin were strongly associated with a reduced risk for macular degeneration (Seddon et al. 1994).

Safety / Dosage

There are no known adverse side effects associated with dietary supplements containing lutein or zeaxanthin when used at recommended levels. Most supplements should be taken with a meal to lessen he chance of causing stomach upset and to increase their digestion and absorption (bioavailability). From studies of ARMD rates and dietary intake, it appears that diets providing about 6 milligrams (mg) of lutein per day can reduce ARMD prevalence by nearly half. Eating more of the carotenoid-rich foods mentioned above should be the first step to increase lutein intake. Unfortunately, recent diet surveys have indicated that consumption of these foods has dropped more than 20% in the two groups at highest risk for ARMD (women and elderly). As many carotenoids are rapidly cleared from the body, it is logical to consider splitting daily intake into two doses (3mg with breakfast and 3mg with dinner).

References

1.Alves-Rodrigues A, Shao A. The science behind lutein. Toxicol Lett. 2004 Apr 15;150(1):57-83.

2.Bartlett H, Eperjesi F. Age-related macular degeneration and nutritional supplementation: a review of randomised controlled trials. Ophthalmic Physiol Opt. 2003 Sep;23(5):383-99.

3.Beatty S, Nolan J, Kavanagh H, O'Donovan O. Macular pigment optical density and its relationship with serum and dietary levels of lutein and zeaxanthin. Arch Biochem Biophys. 2004 Oct 1;430(1):70-6.

4.Blodi BA. Nutritional supplements in the prevention of age-related macular degeneration. Insight. 2004 Jan-Mar;29(1):15-6; quiz 17-8.

5.Bone RA, Landrum JT, Dixon Z, Chen Y, Llerena CM. Lutein and zeaxanthin in the eyes, serum and diet of human subjects. Exp Eye Res. 2000 Sep;71(3):239-45.

6.Bone RA, Landrum JT, Friedes LM, Gomez CM, Kilburn MD, Menendez E, Vidal I, Wang W. Distribution of lutein and zeaxanthin stereoisomers in the human retina. Exp Eye Res. 1997 Feb;64(2):211-8.

7.Castenmiller JJ, West CE, Linssen JP, van het Hof KH, Voragen AG. The food matrix of spinach is a limiting factor in determining the bioavailability of beta-carotene and to a lesser extent of lutein in humans. J Nutr. 1999 Feb;129(2):349-55.

8.Davies NP, Morland AB. Macular pigments: their characteristics and putative role. Prog Retin Eye Res. 2004 Sep;23(5):533-59.

9.Granado F, Olmedilla B, Blanco I. Nutritional and clinical relevance of lutein in human health. Br J Nutr. 2003 Sep;90(3):487-502.

10.Gruber M, Chappell R, Millen A, LaRowe T, Moeller SM, Iannaccone A, Kritchevsky SB, Mares J. Correlates of serum lutein + zeaxanthin: findings from the Third National Health and Nutrition Examination Survey. J Nutr. 2004 Sep;134(9):2387-94.

11.Hammond BR Jr, Johnson EJ, Russell RM, Krinsky NI, Yeum KJ, Edwards RB, Snodderly DM. Dietary modification of human macular pigment density. Invest Ophthalmol Vis Sci. 1997 Aug;38(9):1795-801.

12.Handelman GJ, Nightingale ZD, Lichtenstein AH, Schaefer EJ, Blumberg JB. Lutein and zeaxanthin concentrations in plasma after dietary supplementation with egg yolk. Am J Clin Nutr. 1999 Aug;70(2):247-51.

13.Johnson EJ, Hammond BR, Yeum KJ, Qin J, Wang XD, Castaneda C, Snodderly DM, Russell RM. Relation among serum and tissue concentrations of lutein and zeaxanthin and macular pigment density. Am J Clin Nutr. 2000 Jun;71(6):1555-62.

14.Koh HH, Murray IJ, Nolan D, Carden D, Feather J, Beatty S. Plasma and macular responses to lutein supplement in subjects with and without age-related maculopathy: a pilot study. Exp Eye Res. 2004 Jul;79(1):21-7.

15.Landrum JT, Bone RA, Joa H, Kilburn MD, Moore LL, Sprague KE. A one year study of the macular pigment: the effect of 140 days of a lutein supplement. Exp Eye Res. 1997 Jul;65(1):57-62.

16.Moeller SM, Jacques PF, Blumberg JB. The potential role of dietary xanthophylls in cataract and age-related macular degeneration. J Am Coll Nutr. 2000 Oct;19(5 Suppl):522S-527S.

17.Molldrem KL, Li J, Simon PW, Tanumihardjo SA. Lutein and beta-carotene from lutein-containing yellow carrots are bioavailable in humans. Am J Clin Nutr. 2004 Jul;80(1):131-6.

18.Mozaffarieh M, Sacu S, Wedrich A. The role of the carotenoids, lutein and zeaxanthin, in protecting against age-related macular degeneration: A review based on controversial evidence. Nutr J. 2003 Dec 11;2(1):20.

19.Pratt S. Dietary prevention of age-related macular degeneration. J Am Optom Assoc. 1999 Jan;70(1):39-47.

20.Riso P, Brusamolino A, Ciappellano S, Porrini M. Comparison of lutein bioavailability from vegetables and supplement. Int J Vitam Nutr Res. 2003 May;73(3):201-5.

21.Roodenburg AJ, Leenen R, van het Hof KH, Weststrate JA, Tijburg LB. Amount of fat in the diet affects bioavailability of lutein esters but not of alpha-carotene, beta-carotene, and vitamin E in humans. Am J Clin Nutr. 2000 May;71(5):1187-93.

22.Seddon JM, Ajani UA, Sperduto RD, Hiller R, Blair N, Burton TC, Farber MD, Gragoudas ES, Haller J, Miller DT, et al. Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group. JAMA. 1994 Nov 9;272(18):1413-20.

23.Sommerburg O, Keunen JE, Bird AC, van Kuijk FJ. Fruits and vegetables that are sources for lutein and zeaxanthin: the macular pigment in human eyes. Br J Ophthalmol. 1998 Aug;82(8):907-10.

24.Sommerburg OG, Siems WG, Hurst JS, Lewis JW, Kliger DS, van Kuijk FJ. Lutein and zeaxanthin are associated with photoreceptors in the human retina. Curr Eye Res. 1999 Dec;19(6):491-5.

EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.