RBI Vision Performance by Vitamin Science Inc.

Age-related cognitive decline. Oral astaxanthin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small study in healthy adults over 40 years of age with mild forgetfulness shows that taking a specific combination supplement (BGG Japan Co.) containing astaxanthin 9 mg and tocotrienols 50 mg daily for 12 weeks might improve composite and verbal memory when compared with placebo (105099). This study was funded by the supplement manufacturer.
Age-related macular degeneration (AMD). Oral astaxanthin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with non-advanced AMD shows that a specific combination product (Azyr, Sifi S.p.A.) containing astaxanthin 4 mg, lutein, zeaxanthin, vitamin E, vitamin C, zinc, and copper, taken daily for 12 months, improves selective dysfunction in the central retina, but does not improve dysfunction in the peripheral retinal areas, when compared with baseline (19196). The validity of this finding is limited by the lack of a comparator group.
Aging skin. Small studies suggest that oral and topical astaxanthin may be beneficial in aging skin; however, there is conflicting evidence regarding its effects on wrinkles. Details: Small studies in middle-aged adults show that taking astaxanthin (Astavita Astaxanthin, Astavita; AstaReal Oil 50F, Fuji Chemical Industry Co., Ltd.) 2-3 mg orally twice daily for 6-8 weeks improves elasticity, fine lines, wrinkles, and skin moisture when compared with placebo (19561,91734). However, a meta-analysis of small clinical studies in healthy adults shows that taking oral astaxanthin 2-12 mg daily for 4-16 weeks modestly improves moisture content and skin elasticity, but has no effect on wrinkle depth, when compared with placebo (107961). The validity of this meta-analysis is limited due to the population heterogeneity and variety of astaxanthin formulations utilized. In addition to oral astaxanthin, one study also used topical astaxanthin 0.094% (AstaTROL-Hp, Fuij Chemical Industry Co., Ltd.) 1 mL applied twice daily (91734). A systematic review of two very small, nonblinded studies in healthy adults suggests that topical application, either in combination with oral astaxanthin or alone, might have anti-aging skin effects when used for 2-3 weeks (107961).
Alzheimer disease. Although there is interest in using oral astaxanthin for Alzheimer disease, there is insufficient reliable information about the clinical effects of astaxanthin for this condition.
Athletic performance. Small studies suggest that oral astaxanthin may improve some aspects of athletic performance. Details: Two small studies in trained cyclists show that taking astaxanthin (Fuji Health Science, Inc. or AstaReal) 4-12 mg daily for 1 or 4 weeks decreases the time to complete a 20-40 km cycling trial by about 50-100 seconds when compared with placebo (91735,105096). However, a larger study in trained cyclists shows that taking astaxanthin (BioReal) 20 mg, vitamin C 300 mg, and vitamin E 50 mg daily for 4 weeks does not decrease time needed to complete a predetermined amount of cycling work (a timed trial) when compared with placebo (91738). Reasons for the discrepancies are not clear but may relate to the fitness level of the athletes in the studies or the differences in timed trial protocols used in the studies.
Carpal tunnel syndrome. Oral astaxanthin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a combination of astaxanthin 4 mg, lutein, beta-carotene, and vitamin E (BioAstin, Cyanotech) orally 3 times daily for 8 weeks does not reduce the rate or duration of pain due to carpal tunnel syndrome when compared with placebo (19164).
Diabetes. It is unclear if oral astaxanthin is beneficial for diabetes. Details: A small clinical trial in adults with diabetes shows that taking astaxanthin (Nature Vision) 8 mg daily for 8 weeks does not reduce levels of cholesterol or fasting blood glucose or reduce diastolic blood pressure when compared with placebo. However, there were some modest beneficial effects on visceral fat, triglyceride level, and systolic blood pressure (109778).
Dry eye. It is unclear if oral astaxanthin is beneficial for dry eye syndrome. Details: A clinical study in adults and elderly patients with mild to moderate dry eye syndrome shows that taking oral astaxanthin 6 mg twice daily for 30 days improves symptom severity, tear break-up time, fluorescein break-up time, and meibomian gland dysfunction, but not visual acuity or intraocular pressure, when compared with baseline (107962). The validity of these findings is limited by the lack of a comparator group.
Dyspepsia. It is unclear if oral astaxanthin improves symptoms of dyspepsia. Details: One clinical study in adults with functional dyspepsia with or without Helicobacter pylori infection shows that taking astaxanthin (AstaCarox, AstaReal AB) 16 mg or 40 mg daily for 4 weeks does not reduce indigestion, pain, or H. pylori counts when compared with placebo. However, astaxanthin 40 mg daily may reduce reflux in H. pylori-positive patients (19165).
Exercise-induced muscle damage. Small clinical studies in trained athletes suggest that oral astaxanthin may not improve markers of muscle damage from exercise. Details: A small study in professional male soccer players shows that taking astaxanthin 4 mg daily for 90 days does not seem to reduce exercised-induced biomarkers of muscle damage, such as creatinine kinase, when compared with placebo (91739). Taking a combination of astaxanthin 4 mg and lutein 480 mg (BioAstin, Cyanotech) daily for 3 weeks also did not reduce creatinine kinase levels after exercise in trained athletes when compared with placebo (safflower oil) (19199).
Exercise-induced muscle soreness. Oral astaxanthin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small study in resistance trained athletes shows that taking a combination of astaxanthin 4 mg and lutein 480 mg (BioAstin, Cyanotech) daily for 3 weeks does not reduce muscle soreness or improve muscle performance 96 hours after exercise when compared with placebo (safflower oil) (19199).
Fatigue. Oral astaxanthin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in healthy patients shows that taking a specific combination product (ASTOTS, Fujifilm Co.) containing astaxanthin 6 mg and sesamin 10 mg after breakfast daily for 4 weeks does not improve overall fatigue after completion of mental and physical tasks when compared with placebo (98769).
Heart failure. Oral astaxanthin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with heart failure with reduced left ventricular ejection fraction (LVEF) shows that taking a specific supplement containing astaxanthin 12 mg, tocotrienol 40 mg, and L-ascorbic acid 2-glucoside 30 mg (AstaReal ACT, AstaReal Co., Ltd.) daily for 3 months may increase LVEF from 34% to 38% and modestly increase exercise tolerance as measured by the six-minute walk test when compared with baseline (105097). The validity of these findings is limited by the lack of a comparator group. Furthermore, this study was funded by the supplement manufacturer.
Hyperlipidemia. Small clinical studies suggest that oral astaxanthin is not beneficial for reducing cholesterol levels. Details: One small clinical study in adults with mild hyperlipidemia shows that taking astaxanthin (AstaReal Astaxanthin, Fuji Chemical Industry) 12 mg or 18 mg daily for 12 weeks reduces triglyceride levels, while taking 6 mg or 12 mg daily increases high-density lipoprotein (HDL) cholesterol levels, when compared with placebo. However, total cholesterol and low-density lipoprotein (LDL) cholesterol levels were not affected (19167). Meta-analyses of small clinical studies mostly in adults without hyperlipidemia have also been conducted. One shows that taking astaxanthin 4-18 mg daily for up to 12 weeks does not reduce total or LDL cholesterol levels, but may increase HDL cholesterol levels, when compared with control (105100). A more recent analysis shows that taking astaxanthin 4-20 mg daily for up to 6 months has no beneficial effects on blood lipid levels and might actually increase levels of LDL cholesterol (109776).
Hypertension. It is unclear if oral astaxanthin reduces blood pressure. Details:A meta-analysis of four small clinical trials shows that taking astaxanthin does not have a clinically beneficial effect on systolic or diastolic blood pressure (109776). However, none of the trials were conducted in patients with hypertension.
Impaired glucose tolerance (prediabetes). It is unclear if oral astaxanthin is beneficial in patients with prediabetes. Details: A small clinical study in healthy adults and adults with prediabetes shows that taking oral astaxanthin 12 mg daily for 12 weeks improves glycated hemoglobin (HbA1c) when compared with baseline, but not when compared with placebo. Insulin sensitivity and postprandial glucose levels were also improved when compared with baseline, but no statistical comparison to the placebo group was conducted (107965). The validity of this study is limited due to unclear reporting.
Infertility. It is unclear if oral astaxanthin improves reproductive outcomes in patients with infertility due to endometriosis or polycystic ovary syndrome (PCOS). Details: A small clinical study in adults with infertility secondary to moderate or severe endometriosis undergoing assisted reproductive therapy in Iran shows that taking astaxanthin (AstaReal, AstaReal Co.) 6 mg daily for 12 weeks improves the numbers of oocytes retrieved, mature oocytes, and high-quality embryos but not the quantity of immature oocytes, fertilization rate, number of transferred embryos, or clinical pregnancy rate when compared with placebo (112434). Similarly, a small clinical study also conducted in Iran in patients with infertility due to PCOS undergoing assisted reproductive therapy shows that taking astaxanthin (Algalife Pure astaxanthin) 8 mg daily for 40 days prior to egg retrieval modestly improves the high-quality embryo rate, but not the total number of embryos or the clinical pregnancy rate, when compared with placebo (109775).
Male infertility. It is unclear if oral astaxanthin improves male infertility. Details: A small low-quality clinical study in males with infertility who are participating in intra-uterine insemination shows that taking astaxanthin (AstaCarox, AstaReal AB) 16 mg daily for 3 months does not seem to increase sperm count and quality, but might result in a higher total pregnancy rate of 23% compared with a 3.6% rate in the placebo group (19197). The validity of this finding is limited by poor study methodology and differences between treatment groups. Another small clinical study in males with infertility and oligospermia shows that taking astaxanthin (Astasan, Sensilab) 16 mg daily does not increase sperm concentration or sperm motility when compared with placebo (105098).
Menopausal symptoms. Although there is interest in using oral astaxanthin for menopausal symptoms, there is insufficient reliable information about the clinical effects of astaxanthin for this purpose.
Metabolic syndrome. Although there is interest in using oral astaxanthin for metabolic syndrome, there is insufficient reliable information about the clinical effects of astaxanthin for this condition.
Nonalcoholic fatty liver disease (NAFLD). Although there is interest in using oral astaxanthin for NAFLD, there is insufficient reliable information about the clinical effects of astaxanthin for this condition.
Osteoarthritis. Oral astaxanthin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with mild knee or hip osteoarthritis shows that taking a combination product containing astaxanthin 2 mg, krill oil, and hyaluronic acid daily for 12 weeks (FlexPro MD, Valensa) reduces joint pain and stiffness and improves objective and subjective measures of joint function but does not improve overall physical function when compared with placebo (112432). It is unclear if these effects are due to astaxanthin, other ingredients, or the combination.
Obesity. Although there is interest in using oral astaxanthin for weight loss, there is insufficient reliable information about the clinical effects of astaxanthin for this purpose.
Parkinson disease. Although there is interest in using oral astaxanthin for Parkinson disease, there is insufficient reliable information about the clinical effects of astaxanthin for this condition.
Physical performance. It is unclear if oral astaxanthin improves physical performance in older adults. Details: A small clinical trial in healthy nursing home residents shows that taking astaxanthin (AstaReal) 12 mg twice daily for 16 weeks, in combination with vitamin E 40 mg and vitamin C 30 mg daily, increases the 6-minute walking distance by about 38 meters, a significant increase when compared with placebo containing vitamin E and vitamin C. However, there was no effect on muscle strength (109777). Another small clinical trial in healthy, older adults (aged 65-85 years) undergoing exercise endurance testing shows that a specific combination product (AstaReal; Fuji Health Science, Inc) containing astaxanthin 12 mg, tocotrienol 10 mg, and zinc 6 mg, taken as 2 capsules daily for 12 weeks, reduces the respiratory exchange ratio, but does not improve leg muscle endurance or perceived exertion, when compared with placebo. In a subgroup analysis of males, but not females, those taking astaxanthin had a greater total exercise efficiency when compared with placebo (107963).
Rheumatoid arthritis (RA). Oral astaxanthin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with RA shows that taking a supplement containing astaxanthin 4 mg, lutein 40 mcg, vitamin A 65 IU, vitamin E 50 IU, and safflower oil 460 mg (BioAstin, Cyanotech) three times daily for 8 weeks reduces pain and improves satisfaction by approximately 40% when compared with placebo (94125).
Stroke. Although there is interest in using oral astaxanthin for recovery from stroke, there is insufficient reliable information about the clinical effects of astaxanthin for this purpose.
Sunburn. It is unclear if oral astaxanthin might help to prevent sunburn. Details: A very small clinical study in Japanese adults shows that taking astaxanthin (Astots, Fujifilm Corporation) 4 mg daily for 9 weeks might increase skin tolerance to ultraviolet (UV) light when compared with placebo (96884). It is unclear if this translates to a lower risk of sunburn. More evidence is needed to rate astaxanthin for these uses.

Alzheimer disease. Although there has been interest in using oral black currant berry for Alzheimer disease, there is insufficient reliable information about the clinical effects of black currant for this purpose.
Atopic dermatitis (eczema). Topical black currant seed oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in children aged 2-18 years with atopic dermatitis shows that using a specific cream containing black currant seed oil, sunflower oil, and balloon vine (Defensil), with added dexpanthenol and ceramide, twice daily for 4 weeks, improves atopic dermatitis severity scores similarly to urea 5% cream. About 38% of patients had a 50% improvement in severity score with the combination cream, compared with 35% with urea cream (105538).
Colic. Although there has been interest in using oral black currant leaf for colic, there is insufficient reliable information about the clinical effects of black currant for this purpose.
Common cold. Although there has been interest in using oral black currant berry for common cold, there is insufficient reliable information about the clinical effects of black currant for this purpose.
Cough. Although there has been interest in using oral black currant leaf for cough, there is insufficient reliable information about the clinical effects of black currant for this purpose.
Diarrhea. Although there has been interest in using oral black currant leaf for diarrhea, there is insufficient reliable information about the clinical effects of black currant for this purpose.
Dry eye. Oral black currant has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in adults with dry eye disease shows that taking a specific combination product containing black currant 100 mg, L-carnitine 50 mg, elderberry fruit extract 300 mg, zinc 10 mg, and Eleutherococcus root 50 mg (Meramirt CM) orally once daily improves dry eye symptom scores when compared with no intervention. Contrast sensitivity scores also improved when compared with baseline in the treated group, but not in the control group (111295). It is unclear if this effect is due to black currant, other ingredients, or the combination.
Dysmenorrhea. Although there has been interest in using oral black currant seed oil for dysmenorrhea, there is insufficient reliable information about the clinical effects of black currant for this purpose.
Glaucoma. It is unclear if oral black currant is beneficial in patients with glaucoma. Details: Preliminary clinical research in adults with glaucoma shows that taking black currant anthocyanins 50 mg orally daily for 4 weeks decreases intraocular pressure (IOP) by 1.5 mmHg when compared with placebo (93696). However, other preliminary clinical research in patients with open-angle glaucoma shows that taking black currant anthocyanins 50 mg orally daily along with standard medications for glaucoma for 24 months does not improve IOP when compared with placebo (93695). Preliminary subgroup analyses suggest that patients taking one or less antiglaucoma medications, but not more than one, may benefit the most from black currant (93695,93696).
Gout. Although there has been interest in using oral black currant leaf for gout, there is insufficient reliable information about the clinical effects of black currant for this purpose.
Hyperlipidemia. It is unclear if oral black currant seed oil is beneficial in patients with hyperlipidemia. Details: Preliminary clinical research in adults with hyperlipidemia shows that taking black currant seed oil 18 grams orally twice daily for 6 weeks reduces total cholesterol by about 16%, reduces triglycerides by about 34%, and increases high-density lipoprotein (HDL) cholesterol by about 35% when compared with baseline (17638). However, the validity of this study is limited by the lack of a comparator group.
Hypertension. It is unclear if oral black currant seed oil is beneficial in patients with hypertension. Details: Preliminary clinical research in males with borderline hypertension shows that taking black currant seed oil 6 grams orally daily for 8 weeks does not reduce blood pressure when compared with safflower oil 6 grams daily. However, when stress is induced by a mental arithmetic exercise, black currant seed oil appears to induce a 40% reduction in systolic and diastolic blood pressure elevations in these patients (35994).
Influenza. Although there has been interest in using oral black currant berry for influenza, there is insufficient reliable information about the clinical effects of black currant for this purpose.
Insect bite. Although there has been interest in using topical black currant leaf for insect bite, there is insufficient reliable information about the clinical effects of black currant for this purpose.
Japanese cedar pollinosis. It is unclear if oral black currant extract is beneficial in patients with Japanese cedar pollinosis. Details: Preliminary clinical research in patients with Japanese cedar pollinosis shows that taking a black currant polysaccharide extract 540 mg orally twice daily for 8 weeks does not improve nasal symptom scores or swelling when compared with placebo (17635).
Liver disease. Although there has been interest in using oral black currant leaf for liver disease, there is insufficient reliable information about the clinical effects of black currant for this purpose.
Menopausal symptoms. Although there has been interest in using oral black currant seed oil for menopausal symptoms, there is insufficient reliable information about the clinical effects of black currant for this purpose.
Muscle fatigue. It is unclear if oral black currant juice extract is beneficial in patients with muscle fatigue. Details: Preliminary clinical research in office workers shows that black currant juice extract, containing 10.83% anthocyanins, taken once orally and dosed as anthocyanins 17 mg/kg, reduces muscle stiffness scores after typing for 30 minutes when compared with placebo (17633).
Osteoarthritis. Although there has been interest in using oral black currant leaf for osteoarthritis, there is insufficient reliable information about the clinical effects of black currant for this purpose.
Peripheral arterial disease (PAD). Although there has been interest in using oral black currant juice for PAD, there is insufficient reliable information about the clinical effects of black currant for this purpose.
Premenstrual syndrome (PMS). Although there has been interest in using oral black currant seed oil for PMS, there is insufficient reliable information about the clinical effects of black currant for this purpose.
Rheumatoid arthritis (RA). It is unclear if oral black currant seed oil is beneficial in patients with RA. Details: A small clinical study in patients with RA shows that taking black currant seed oil 10.5 grams orally daily for 24 weeks reduces tenderness scores when compared with placebo (35990).
Rhinosinusitis. Oral black currant has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients over 12 years of age with chronic sinusitis shows that taking a combination product containing black currant, Boswellia serrata, bromelain, and vitamin D (Flogostop Forte, Humana Italia) with inhaled corticosteroids daily for 30 days reduces rhinorrhea, hyperemia of mucosa, and local inflammation when compared with inhaled corticosteroids alone (111501). It is unclear if these findings are due to black currant, other ingredients, or the combination.
Seizures. Although there has been interest in using oral black currant leaf for seizures, there is insufficient reliable information about the clinical effects of black currant for this purpose.
Upper respiratory tract infection (URTI). Although there has been interest in using oral black currant berry for URTIs, there is insufficient reliable information about the clinical effects of black currant for this purpose.
Urinary tract infections (UTIs). Although there has been interest in using oral black currant leaf for UTIs, there is insufficient reliable information about the clinical effects of black currant for this purpose.
Venous insufficiency. Although there has been interest in using oral black currant for venous insufficiency, there is insufficient reliable information about the clinical effects of black currant for this purpose.
Wound healing. Although there has been interest in using topical black currant leaf for wound healing, there is insufficient reliable information about the clinical effects of black currant for this purpose. More evidence is needed to rate black currant for these uses.

LUTEIN

POSSIBLY EFFECTIVE

Age-related macular degeneration (AMD). When used alone or in combination with other ingredients, oral lutein seems to improve some aspects of vision in patient with AMD. However, it does not seem to slow the progression of AMD. Details: Epidemiological research has found that people who consume higher amounts of lutein plus zeaxanthin in the diet have a reduced risk of developing AMD (219,2394,60238,106353). The association between intake of lutein specifically and the development of AMD is not clear; however, dietary lutein levels are much higher than dietary zeaxanthin levels. Although one study found no association between increased dietary lutein consumption and a reduced risk for age-related maculopathy, people in this study already had high lutein intake at baseline (14007). Some research has assessed whether lutein supplements can reduce symptoms and progression of existing AMD. Clinical research, including pooled analyses, in adults with AMD shows that taking supplemental lutein 10-20 mg daily for up to 36 months modestly improves some aspects of vision, such as macular pigment optical density, the ability of the eyes to adapt to varying light conditions (glare recovery), the ability to see details of near objects (near vision acuity), and the ability to see under low-contrast conditions (contrast sensitivity) (11798,48213,60185,60242,60245,60268,60270,60280,90678,91160)(91165,97225,102887,106366). Meta-analyses of these and other studies shows that taking lutein or a related xanthophyll carotenoid (zeaxanthin or meso-zeaxanthin) improves macular optical density when compared with placebo in patients with or without AMD. Treatment duration of at least 3 months, doses greater than 5 mg, and/or combination treatment with all three carotenoids are associated with a greater improvement in macular optical density (97225,106366). However, lutein supplements do not appear to affect the progression of AMD (60281). A meta-analysis of 6 studies shows that taking lutein supplements for 0.5-5 years does not reduce the risk of visual loss or progression to late-stage AMD when compared with placebo (95839). Lutein has also been evaluated in combination with other ingredients, with conflicting findings. Although not all research agrees, lutein-containing combination supplements might improve some symptoms of AMD (19196,60134,60180,60207,60237,60244,97226). A specific supplement (AZYR SIFI) containing lutein 10 mg, vitamin C 180 mg, vitamin E 30 mg, zinc 22.5 mg, copper 1 mg, zeaxanthin 1 mg, and astaxanthin 4 mg has been used daily for 1-2 years in some research with moderate evidence of benefit (19196,60244). Taking lutein 10 mg plus zeaxanthin 2 mg in addition to the original Age-Related Eye Disease Study (AREDS) formulation (vitamins C and E, beta carotene, and zinc) does not seem to prevent the progression to advanced AMD more than the AREDS formulation alone. However, this progression was modestly inhibited in individuals with low dietary intakes of lutein and zeaxanthin. While progression to late AMD was only modestly inhibited at 5 years when these doses of lutein and zeaxanthin were included in a revised formulation devoid of beta-carotene (AREDS2) (60281), results of an additional 5 years of follow up showed that this revised formulation reduces the risk of progression to late AMD by 15% when compared with the formulation containing beta-carotene (108615). In first-generation offspring of parents with neovascular AMD, taking lutein 10 mg, zeaxanthin 2 mg, vitamin C 180 mg, vitamin E 30 mg, zinc 15 mg, and copper 1 mg daily for 6 months does not improve the macular pigment optical density (106347). Reasons for these discrepancies are not clear but may relate to lutein dose, dietary lutein intake, treatment duration, or the other ingredients included in the combination products.
Cataracts. Increased dietary lutein seems to reduce the odds of developing cataracts. It is unclear if oral lutein supplementation is beneficial in those who already have cataracts. Details: Observational research and a meta-analysis of this evidence suggests that higher blood levels and/or higher dietary intake of lutein are associated with a 25% lower odds of developing age-related cataracts, and more specifically, a 25% to 27% decreased risk of developing nuclear cataracts (90944,91161,91162,112095). Population research has also found that people who consume higher amounts of lutein (6.9-11.7 mg daily) as part of their diet have a reduced risk of developing severe cataracts that require surgical removal (2395,3219,3220). Clinical research shows that taking lutein 10 mg and zeaxanthin 2 mg per day orally for an average of 4.7 years decreases the risk of needing cataract surgery by 32% in patients with low dietary intake of lutein and zeaxanthin; however, it doesn't benefit patients with higher dietary intake of lutein and zeaxanthin (94703). Some evidence shows that supplemental lutein might benefit patients who already have cataracts. Preliminary clinical research in adults with grade 2 or 3 senile cataracts shows that taking lutein 15 mg orally three times weekly for up to 2 years can improve the ability to see clearly when compared to baseline (60133).

POSSIBLY INEFFECTIVE

Bronchopulmonary dysplasia. Oral lutein does not seem to prevent bronchopulmonary dysplasia in preterm and low birth weight infants. Details: Clinical research shows that giving preterm and low birth weight infants a specific product (LUTEINofta, SOOFT Italia SpA) containing lutein 0.14 mg and zeaxanthin 0.0006 mg orally once daily, starting at birth and continuing until 36 weeks corrected gestational age, does not decrease the incidence of bronchopulmonary dysplasia when compared with placebo (91163).
Necrotizing enterocolitis (NEC). Oral lutein does not seem to prevent NEC in preterm and low birth weight infants. Details: Clinical research shows that giving preterm and low birth weight infants a specific product (LUTEINofta, SOOFT Italia SpA) containing lutein 0.14 mg and zeaxanthin 0.0006 mg orally once daily, starting at birth and continuing until 36 weeks corrected gestational age, does not decrease the incidence of NEC when compared with placebo (91163).
Retinitis pigmentosa. Oral lutein does not seem to improve vision or slow down retinal degeneration in patients with this condition. Details: While some preliminary clinical evidence suggests that oral lutein might be helpful in the treatment of retinitis pigmentosa (10279), most clinical research shows that taking lutein does not improve vision or other markers of retinal degeneration in patients with retinitis pigmentosa (60117,60165,60225).
Retinopathy of prematurity. Oral lutein does not seem to prevent retinopathy of prematurity in preterm and low birth weight infants. Details: Clinical research in preterm and low birth weight infants shows that giving 0.5 mL or 1.8 mL/kg of a specific product (LUTEINofta, SOOFT Italia SpA) providing lutein 0.14 mg, or giving 0.5 mg/kg plus zeaxanthin 0.0006 mg or 0.02 mg/kg orally once daily, starting at birth and continuing until 36-40 weeks corrected gestational age, does not decrease the incidence or severity of retinopathy of prematurity when compared with placebo (60240,60243,91163,102889).

Age-related cognitive decline. It is unclear if oral lutein is beneficial for attenuating cognitive decline in older adults. Details: Clinical research in adults 40-75 years old shows that taking lutein 10 mg with zeaxanthin 2 mg daily for 6 months improves some, but not all, measures of visual memory when compared with placebo. However, other measures of memory and cognitive function were not improved (109763). Preliminary clinical research in older adults shows that taking the same dose of lutein and zeaxanthin for one year modestly improves some measures of cognitive function, such as complex attention and cognitive flexibility, when compared with placebo (106367). Other preliminary clinical research in older females shows that taking lutein 12 mg alone or with docosahexaenoic acid (DHA) 800 mg daily for 4 months can improve verbal fluency and memory scores when compared to baseline (48216). Also, some observational research in patients 50 years and older has found that higher dietary lutein and zeaxanthin intake is associated with greater word recall when compared with lower intake (102891). However, clinical research in patients over 60 years old shows that taking lutein 10 mg with zeaxanthin 2 mg daily for 5 years in addition to vitamins C and E, beta-carotene, and zinc (AREDS) does not improve markers of cognitive function, such as memory and verbal fluency, when compared with AREDS alone (94702). More research is needed to determine whether lutein is beneficial for specific measures of cognitive function in older adults.
Alzheimer disease. Oral lutein has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with mild to moderate Alzheimer disease shows that taking lutein 10 mg, zeaxanthin 2 mg, meso-zeaxanthin 10 mg, fish oil 1 gram (providing docosahexaenoic acid 500 mg and eicosapentaenoic acid 150 mg), and vitamin E 15 mg (Memory Health) daily for 12 months does not affect disease severity when compared with placebo. However, there were modest increases the number of patients experiencing either an improvement or an attenuated decline in memory and mood (109764). The effect of lutein alone is unclear.
Amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease). It is unclear if oral lutein is beneficial for ALS prevention. Details: Population research has found that higher dietary intake of lutein is associated with a 21% lower risk of developing ALS when compared with lower dietary intake (90412). It is unknown if supplemental lutein has any effect on the risk of developing ALS.
Asthenopia (eye strain). It is unclear if oral lutein is beneficial for eye strain. Details: Preliminary clinical research shows that some combination lutein supplements might reduce symptoms of eye strain. Results from one clinical trial show that taking a combination product containing lutein, zeaxanthin, and black currant extract daily for 2 weeks improves visual fatigue and eye stress when compared with placebo in patients completing a two-hour visual proof reading task (60214). Other clinical research shows that taking lutein 17.5 mg plus omega-3 fatty acids (standardized to contain docosahexaenoic acid 783 mg and eicosapentaenoic acid 162 mg) and bilberry extract (standardized to contain anthocyanidin 59 mg) daily for 4 weeks reduces symptoms of eye strain when compared with placebo (35470). The effect of lutein alone on eye strain is unclear.
Asthma. It is unclear if oral lutein is beneficial for asthma prevention. Details: Population research has found that a higher dietary intake of lutein plus zeaxanthin is associated with up to 30% lower odds of having asthma when compared with a lower dietary intake (109765). The effects of lutein intake alone or lutein supplementation are unclear.
Cardiovascular disease (CVD). Eating more lutein in the diet seems to reduce the risk of CVD. However, taking oral lutein supplements does not seem to prevent CVD events or mortality. Details: One observational study has found that increased intake of dietary lutein is marginally associated with a reduced risk of developing coronary heart disease (14108). A meta-analysis including this and other studies shows that high dietary lutein intake or high lutein serum concentrations are associated with a 12% reduction in the incidence of coronary heart disease, an 18% reduction in stroke, and a 25% reduction in the incidence of metabolic syndrome when compared with low lutein intake or serum concentrations (97227). However, clinical research shows that taking lutein 10 mg plus zeaxanthin 2 mg daily for an average of 4.8 years does not decrease the risk of CVD-related mortality or cardiovascular events such as stroke, myocardial infarction, or angina when compared with no supplementation in patients 50-85 years old (94701). Unlike the analysis above, individual cardiovascular outcomes were not separately evaluated in this study. The effect of lutein on CVD in younger patients or in doses greater than 10 mg is unknown.
Central serous retinopathy. Oral lutein has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a supplement containing lutein 15 mg, vitamin C 288 mg, vitamin E 150 IU, zinc 9 mg, and copper 1.2 mg (Sante Lutax 15, Santen Pharmaceutical Co. Ltd) three times daily after meals for 6 months has no effect on mean best-corrected visual acuity, serous retinal detachment, or subfoveal fluid remission when compared with placebo in patients with central serous retinopathy (97224).
Cervical cancer. It is unclear if oral lutein is beneficial for cervical cancer prevention. Details: Epidemiological research has found that low dietary intake of lutein is not associated with an increased risk for developing cervical cancer (60297).
Child development. It is unclear if oral lutein is beneficial for child development. Details: Epidemiological research has found that a higher dietary intake of lutein in the first and second trimesters of pregnancy is associated with increased verbal intelligence and improved behavior in the child at 6-10 years of age. However, the ability to discriminate between a novel or familiar visual stimulus was reduced at about 6 months of age, and there were no effects on most cognitive outcomes in children aged 3-6 years (107106). Other epidemiological research has found that a higher dietary intake of lutein plus zeaxanthin in children aged 3-6 years may be associated with modestly improved executive function at 6-10 years. However, there were no effects on most cognitive outcomes in children aged 3-6 years or 6-10 years (109761).
Choroideremia. It is unclear if oral lutein is beneficial for improving vision. Details: Preliminary clinical research shows that taking lutein 20 mg daily for 6 months does not improve vision in patients with choroideremia (60124).
Cognitive function. It is unclear if oral lutein is beneficial for improving cognitive function. Details: A meta-analysis of clinical research shows that increased dietary lutein does not improve cognitive function measures, such as attention, executive function, or memory, when compared with placebo or an isocaloric meal (107082). However, the dietary source of lutein used in the included studies was heterogeneous and any conclusions remain unclear. Doses of lutein ranged from 8-12 mg daily, alone or in combination with daily zeaxanthin 2-26 mg and/or meso-zeaxanthin 10 mg and docosahexaenoic acid (DHA) 800 mg (107082). However, some preliminary clinical research in younger adults shows that taking lutein 10 mg and zeaxanthin 2 mg for one year modestly improves some measures of cognitive function, such as spatial memory, when compared with placebo (106348). Also, observational research has found that intake of choline and lutein plus zeaxanthin is positively associated with cognitive flexibility task performance speed. However, this association is not present with the intake of lutein plus zeaxanthin in the absence of choline (106354). Reasons for these discrepancies are not clear but may relate to lutein dose, treatment duration, or the addition of other nutrients to the diet or supplements.
Colorectal cancer. It is unclear if oral lutein is beneficial for colorectal cancer prevention. Details: Some epidemiological research has found that higher dietary intake of lutein is associated with a reduced risk of developing colon cancer (3962). However, most epidemiological research has found that higher dietary intake of lutein is not associated with a reduced risk of colorectal cancer (34481,106372). It is not known if supplemental lutein has any effect on colorectal cancer risk.
Depression. It is unclear if oral lutein is beneficial for depression. Details: A cross-sectional study in 8655 adults with cardiometabolic disease including diabetes, hypertension, coronary heart disease, heart failure, and stroke suggests that higher dietary lutein and zeaxanthin intake is associated with a 31% reduced risk of depression when compared with lower dietary intake. The study also found that adults with depression had lower dietary lutein and zeaxanthin intake than those without depression. Additionally, the study found a nonlinear U-shaped relationship between total dietary carotenoid intake and the risk of depression among patients with cardiometabolic disease, where the risk of depression decreased with increasing total dietary carotenoid intake up until an inflection point where the risk of depression increased with increasing total dietary carotenoid intake (112098). Further research is needed to establish causality.
Diabetes. Observational research suggests that oral lutein may not be beneficial for the prevention of diabetes or diabetic complications. Details: Some epidemiological research has found that low serum levels of carotenoids, including lutein, are associated with impaired glucose tolerance. This may indicate that taking carotenoids such as lutein might reduce the risk of diabetes development (60161). However, population research has found that increasing intake of dietary lutein plus zeaxanthin does not decrease the risk of developing type 2 diabetes (14004,97227). Other epidemiological research in patients with type 2 diabetes has found that an increased serum concentration of lutein is not associated with reduced cardiovascular mortality over 14 years (109768).
Diabetic retinopathy. It is unclear if oral lutein is beneficial in diabetic retinopathy. Details: Preliminary clinical research shows that taking lutein 10 mg daily for 36 weeks has no effect on visual acuity or glare sensitivity in patients with non-proliferative diabetic retinopathy (97223). Observational research in a small group of patients with non-proliferative diabetic retinopathy has also found that taking lutein 4 mg with zeaxanthin 0.5 mg daily for 4 months does not improve visual acuity, contrast sensitivity, or glare sensitivity when compared with zeaxanthin alone (100986).
Esophageal cancer. It is unclear if oral lutein is beneficial for esophageal cancer prevention. Details: Population research has found that people who consume higher amounts of lutein and zeaxanthin in their diet have a 29% lower risk of developing esophageal squamous cell cancer when compared with those with lower intake (91159). It is unknown if supplemental lutein has any effect on esophageal cancer risk.
Exercise-induced muscle soreness. It is unclear if oral lutein is beneficial in relieving muscle soreness due to exercise. Details: Some clinical research shows that taking a specific lutein-containing combination product (BioAstin, Cyanotech Corp.) containing haematococcus algae extract with astaxanthin 4 mg and lutein 480 mg daily for 3 weeks prior to exercise does not significantly reduce post-exercise muscle soreness when compared with placebo (19199). The effect of lutein alone is unclear.
Fractures. It is unclear if oral lutein is beneficial for fracture prevention. Details: A meta-analysis of observational research has found that increased dietary intake of lutein and/or zeaxanthin is not associated with a reduced risk of hip fractures (97228).
Gastric cancer. It is unclear if oral lutein is beneficial for gastric cancer prevention. Details: A meta-analysis of observational research has found that increased dietary intake of lutein and/or zeaxanthin is not associated with a reduced risk of developing gastric cancer (97231).
Glaucoma. Oral lutein has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with open-angle glaucoma shows that taking oral lutein 10 mg, zeaxanthin 2 mg, and meso-zeaxanthin 10 mg daily for 18 months increases macular pigment density, but does not affect visual function, when compared with placebo (109756).
Hyperlipidemia. It is unclear if oral lutein is beneficial for hyperlipidemia. Details: A meta-analysis of clinical research shows that supplementation with lutein does not reduce the levels of total, low-density lipoprotein (LDL), or high-density lipoprotein (HDL) cholesterol when compared with placebo (109757). Most publications included in this analysis evaluated lutein alone in healthy adults or in patients with age-related macular degeneration, two studies combined lutein with another ingredient, and one study evaluated zeaxanthin alone. The effect of lutein in patients with existing hyperlipidemia is unclear.
Infertility. It is unclear if oral lutein is beneficial for infertility. Details: An observational study suggests that there is no association between dietary lutein intake and in-vitro fertilization (IVF) outcomes including good oocyte quality, embryo transfer success rates, clinical pregnancy rates, and successful term pregnancy rates in subfertile couples who are candidates for IVF (112097).
Lung cancer. Research is conflicting whether oral lutein is beneficial for lung cancer prevention. Details: Epidemiological research has found that low serum levels of carotenoids, including lutein, are associated with an increased risk of lung cancer (12874). However, other epidemiological research has found that higher serum levels or higher dietary intake of lutein are not associated with a reduced risk of developing or dying from lung cancer (39690,60090,60160). Another large epidemiological cancer screening trial with a mean follow-up of over 12 years suggests that dietary intake of lutein and zeaxanthin is protective against lung cancer as shown by a non-linear dose response curve, where lower doses of lutein and zeaxanthin are associated with a sharp decrease in the incidence of lung cancer, followed by a more gradual decrease in incidence at higher doses (112096).
Macular telangiectasia type 2. It is unclear if oral lutein is beneficial for macular telangiectasia type 2. Details: In patients with macular telangiectasia type 2, observational research has found that taking a specific combination of lutein 10 mg, meso-zeaxanthin 10 mg, and zeaxanthin 2 mg (MacuShield; Alliance Pharmaceuticals) for at least 6 months, with an average duration of 15.7 months, was associated with a stabilization of visual acuity. Also, the number and size of cavitations in the macula were reduced (106355).
Metabolic syndrome. Oral lutein has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of observational research shows that high dietary lutein intake or high lutein serum concentrations are associated with a 25% reduction in the incidence of metabolic syndrome when compared with low lutein intake or serum concentrations (97227). Additional population research in females shows that the highest dietary intake of lutein plus zeaxanthin is associated with 54% reduced odds of developing metabolic syndrome when compared with the lowest intake. However, when supplements containing lutein plus zeaxanthin were included in the total intake, there was no association with metabolic syndrome (109760).
Myopia. It is unclear if oral lutein is beneficial for myopia. Details: A very small clinical study in adults aged 20-50 years with high myopia shows that taking lutein 20 mg daily for 6 months does not improve macular pigment optical density, visual acuity, contrast sensitivity, or electroretinogram measurements when compared with placebo (112099). The validity of these findings is limited by the very small sample size and short study duration.
Non-Hodgkin lymphoma. It is unclear if oral lutein is beneficial for Non-Hodgkin lymphoma prevention. Details: A meta-analysis of observational population research has found that increased intake of lutein/zeaxanthin in the diet is associated with an 18% lower risk of developing non-Hodgkin lymphoma when compared with low dietary intake. However, no dose-response relationship was reported (97229). It is unknown if supplemental lutein has any effect on non-Hodgkin lymphoma risk.
Obesity. It is unclear if oral lutein is beneficial for obesity. Details: A small clinical trial in obese middle-aged individuals shows that taking lutein 20 mg daily in addition to following a low-calorie diet for 10 weeks does not affect most anthropometric or cardiometabolic indices when compared with a low-calorie diet alone. However, there was a small beneficial effect on body fat and total cholesterol levels (107107).
Pancreatic cancer. It is unclear if oral lutein is beneficial for pancreatic cancer prevention. Details: A meta-analysis of population research has found that increased dietary intake of lutein and/or zeaxanthin is not associated with a reduced risk of pancreatic cancer (97230). The effects of supplemental lutein are unclear.
Parkinson disease. It is unclear if oral lutein is beneficial for Parkinson disease prevention. Details: Population research has found that higher dietary intake of lutein is not associated with the risk of developing Parkinson disease (91164). The effects of supplemental lutein are unclear.
Pre-eclampsia. It is unclear if oral lutein is beneficial for pre-eclampsia prevention. Details: Some epidemiological research has found that high plasma concentrations of lutein are associated with a decreased risk of pre-eclampsia (60142). Other epidemiological research has found that the highest dietary intake of lutein plus zeaxanthin during pregnancy is associated with 68% reduced odds of having pre-eclampsia when compared with the lowest intake (109762). The effects of lutein supplements are unclear.
Respiratory tract infections. It is unclear if oral lutein is beneficial in respiratory tract infection prevention or treatment. Details: Epidemiological research has found that high serum levels of lutein are not associated with a decreased incidence or severity of respiratory tract infections in the elderly (60152). The effects of supplemental lutein are unclear.
Ulcerative colitis. It is unclear if oral lutein is beneficial for ulcerative colitis. Details: In patients in the remission phase of ulcerative colitis, observational research has found that a higher dietary intake of lutein plus zeaxanthin is associated with a reduced incidence of constipation, but not flatulence or feelings of urgency (tenesmus) (106362). The effects of supplemental lutein are unclear.
Visual development. It is unclear if taking oral lutein during pregnancy can improve the visual acuity of the child. Details: Some observational research has found that higher maternal lutein levels are associated with a 22% to 40% lower risk of poor visual acuity in children at 3 years of age when compared with lower maternal lutein levels (102888). However, other epidemiological research has found that dietary intake of lutein plus zeaxanthin during the first or third trimesters of pregnancy is not associated with contrast vision or visual acuity in the child at 11-12 years of age (109759). The effects of lutein supplements are unclear. More evidence is needed to rate lutein for these uses.

SAFFRON

POSSIBLY EFFECTIVE

Alzheimer disease. Oral saffron might modestly improve cognition in patients with Alzheimer disease. Details: Two small clinical trials in patients with probable Alzheimer disease living in Iran shows that taking saffron extract (Green Plants of Life, Co., previously Impiran) 15 mg orally twice daily for 16-22 weeks improves cognitive ability and disease progression when compared with placebo, and is no different for improving cognition when compared with taking donepezil (Aricept) 10 mg daily (17401,93395). Another small clinical study in adults also living in Iran with moderate to severe Alzheimer disease shows that taking saffron extract 30 mg daily for 48 weeks seems to be no different for improving cognition when compared with taking memantine (Namenda) 20 mg (105617). It is unclear if these findings are generalizable to patients in other geographic locations.
Chemotherapy-induced peripheral neuropathy. Oral saffron seems to improve symptoms of chemotherapy-induced peripheral neuropathy, although it is unclear how it compares with standard care. Details: A clinical crossover study in adults with mild to severe chemotherapy-induced peripheral neuropathy shows that taking the saffron constituent crocin 15 mg twice daily for 8 weeks progressively improves pain scores when compared with placebo, with significant improvements appearing after 5 weeks of treatment. During a 2-week washout period, pain scores in the treatment group returned to baseline, suggesting a loss of benefit after discontinuation. This study included patients who were actively receiving chemotherapy and those who had completed or discontinued treatment; however, a separate analysis for each subgroup was not conducted (108904).
Depression. Oral saffron extract seems to improve symptoms of depression when used alone or as an adjunct to conventional antidepressants. Details: Meta-analyses and clinical trials in adults with mild to moderate major depressive disorder show that taking saffron extract 30 mg daily or dried saffron stigma 100 mg daily for 6-12 weeks improves symptoms of depression when compared with control (11024,13103,72434,93399,93404,100140,103928,103931). Saffron extract also seems to be comparable to imipramine 100 mg daily, fluoxetine 10 mg twice daily, citalopram 40 mg daily, or sertraline 100 mg daily (11024,17222,19032,93399,100140,100658,103927). Furthermore, some clinical research shows that taking a specific saffron extract (affron, Pharmactive Biotech Products) 14 mg twice daily for 8 weeks or the saffron constituent, crocin, 15 mg twice daily for 4 weeks, as an adjunct to a selective serotonin reuptake inhibitor (SSRI) also modestly reduces depressive symptoms when compared with placebo (93410,103934). However, other research has produced mixed results, which may be due to the use of different depression scales. An umbrella meta-analysis consisting of 7 separate meta-analyses shows that taking saffron, either alone or with other treatments, improves symptoms of depression when compared with control in studies using the Beck depression inventory criteria, but not in those using the Hamilton depression rating scale, the depression anxiety stress scale, or mixed scales (108911). In general, the validity of the available research is limited by the variety of saffron doses and treatment durations, as well as the fact that most research has been conducted in Iran. It is unclear if saffron is beneficial for comorbid depression and anxiety. A small clinical trial in adults with this condition shows that taking saffron extract 15 mg twice daily for 8 weeks does not improve symptoms of depression, but does improve symptoms of anxiety, when compared with placebo (100137). This study may not have been adequately powered to detect smaller differences between groups. Saffron has also been studied in combination with other ingredients. One clinical trial in adults with major depressive disorder shows that taking saffron 15 mg twice daily in combination with curcumin 250 mg twice daily for 12 weeks does not reduce depressive symptoms when compared with placebo (97359). The validity of this finding may be limited by the large placebo response.

Age-related macular degeneration (AMD). Small studies suggest that oral saffron might slightly improve visual acuity in AMD. Details: Preliminary clinical research in adults 50 years and older with AMD shows that taking saffron extract 20 mg daily for 3 months has a modest effect on visual acuity and some other measurements of retinal health when compared with placebo. This improvement occurred in patients also taking Age-Related Eye Diseases Study (AREDS) supplements or equivalent. However, these small improvements are unlikely to be considered clinically significant (93398,100135).
Antidepressant-induced sexual dysfunction. Small studies suggest that oral saffron may reduce some symptoms of fluoxetine-induced sexual dysfunction. Details: One small clinical study in females with major depression stabilized on fluoxetine 40 mg daily shows that taking saffron extract 30 mg daily for 4 weeks improves arousal, lubrication, and pain during sexual intercourse when compared with placebo (93401). A small clinical study in males with major depression stabilized on fluoxetine 40 mg daily shows that taking saffron extract 30 mg daily improves erectile dysfunction and intercourse satisfaction when compared with placebo (93407). However, taking saffron does not appear to significantly improve desire, overall satisfaction, or orgasm in patients taking fluoxetine (93401,93407).
Antipsychotic-induced metabolic side effects. It is unclear if oral saffron reduces metabolic side effects from antipsychotic treatment. Details: A small clinical study in adults with schizophrenia who are taking olanzapine shows that taking saffron aqueous extract 30 mg daily for 12 weeks, or crocin, a constituent of saffron, 30 mg daily for 6 weeks, reduces fasting blood glucose and the risk of developing metabolic syndrome. At 6 weeks, metabolic syndrome occurred in 0% of patients taking saffron, about 9% of patients taking crocin, and about 27% of patients taking placebo. Levels of cholesterol, HBA1c, and insulin were unchanged (93397).
Anxiety. Small clinical studies suggest that oral saffron might improve anxiety. Details: One preliminary clinical study in adults with type 2 diabetes and comorbid depression-anxiety (CDA) shows that taking saffron extract 15 mg twice daily for 8 weeks improves symptoms of anxiety by 34% when compared with placebo (100137). Other preliminary clinical research in adults with mild to moderate anxiety shows that taking saffron extract 50 mg twice daily for 12 weeks improves symptoms of anxiety by 81%, compared with an improvement of 53% with placebo (93404).
Asthma. There is limited evidence on the oral use of saffron in patients with allergic asthma. Details: A small clinical study in patients with mild to moderate allergic asthma shows that taking saffron extract 100 mg daily for 8 weeks improves symptoms of asthma, but not asthma severity, when compared with placebo. The use of salbutamol was reduced by approximately 50% in patients taking saffron. Saffron also produced modest improvements in waking during the night due to asthma symptoms, shortness of breath during the night, and activity limitation (100141). However, due to the low rate of symptoms at baseline, it is difficult to determine if these improvements are clinically significant.
Athletic performance. It is unclear if oral saffron is beneficial for athletic performance. Details: A small clinical study in healthy, untrained, young adult males shows that taking dried saffron stigma powder 300 mg every evening for 10 days improves muscular force by up to 10% and might improve reaction time when compared with placebo (93406). A very small clinical study in healthy adults suggests that taking crocetin, a constituent of saffron, 15 mg daily for 8 days might improve performance on a 3.5-hour physically exhausting task in males, but not in females, when compared with placebo (19058).
Burning mouth syndrome. It is unclear if oral saffron reduces burning mouth syndrome. Details: A very small clinical study in patients with burning mouth syndrome shows that taking the saffron constituent crocin 15 mg daily for 11 weeks seems to reduce pain to a similar degree as citalopram 20 mg daily (103937).
Cancer. Although there is interest in using oral saffron for cancer, there is insufficient reliable information about the clinical effects of saffron for this condition.
Cough. Although there is interest in using oral saffron for cough, there is insufficient reliable information about the clinical effects of saffron for this purpose.
Diabetes. Research evaluating oral saffron for glycemic control is conflicting. Details: Some clinical research in patients with type 2 diabetes shows that taking saffron extract 30 mg daily, saffron powder 100 mg daily, or drinking black tea stewed with saffron powder 1 gram three times daily, for 2-3 months, does not improve glycated hemoglobin (HbA1c), but might modestly reduce fasting blood glucose, when compared with placebo (99436,100138,103936,108905). The validity of these findings is limited due to differences in glycemic control at baseline and differences in the dose and form of saffron used. A meta-analysis of clinical trials shows that taking saffron, saffron extract, or the constituent crocin for up to 3 months does not improve levels of fasting blood glucose, blood lipids, or HbA1c when compared with placebo or control. However, this research included healthy individuals, as well as patients with type 2 diabetes, metabolic syndrome, coronary artery disease (CAD), schizophrenia, or depression (100139). Patients with type 2 diabetes were not analyzed separately, limiting the applicability of this finding.
Dysmenorrhea. Oral saffron has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in students with dysmenorrhea shows that taking a specific combination product containing saffron, celery seed, and anise extracts (SCA, Gol Daro Herbal Medicine Laboratory) 500 mg three times daily for 3 days reduces the severity and duration of menstrual pain when compared with placebo (17214).
Erectile dysfunction (ED). It is unclear if oral or topical saffron improves ED; the available research is conflicting. Details: Preliminary clinical research in adults with diabetes and ED shows that applying a gel containing saffron 1% to the penis 30 minutes prior to intercourse for one month improves general symptoms when compared with placebo. ED, sexual desire, and orgasmic function improved by 37%, 14%, and 21%, respectively, for those using saffron gel compared to 2%, 2%, and 0%, respectively, for those in the placebo group (93408). A small, open-label study has also shown benefit with dried oral saffron 200 mg daily for 10 days (19057). However, in adults with ED who are naïve to treatment, one small clinical study shows that taking saffron extract 30 mg twice daily by mouth for 12 weeks does not improve symptoms when compared to baseline (93409). These conflicting results may be related to the cause of ED, as well as the route, dose, and form of saffron used.
Exercise-induced muscle soreness. It is unclear if oral saffron reduces muscle soreness from exercise. Details: Preliminary clinical research in healthy but exercise-naïve young adult males shows that taking dried saffron powder 300 mg every evening for 10 days, starting one week before a leg press exercise, reduces delayed muscle soreness about 11-fold when compared with placebo. Saffron appears to be more effective than indomethacin for reducing pain and maintaining muscle force during the 72-hour period post-exercise (93405).
Glaucoma. It is unclear if oral saffron reduces intraocular pressure in patients with glaucoma. Details: A small clinical study in patients with primary open-angle glaucoma shows that taking saffron extract 30 mg daily for 4 weeks, in conjunction with timolol and dorzolamide, reduces intraocular pressure by an additional 16.5% when compared with placebo. After a 4-week washout, intraocular pressure returned to baseline in the saffron group (93400).
Hyperlipidemia. Small studies suggest that oral saffron does not affect lipid levels in most patients; the effect of saffron in adults with diagnosed hyperlipidemia is unclear. Details: A meta-analysis of clinical trials shows that taking saffron, saffron extract, or the constituent crocin for up to 3 months does not reduce levels of total cholesterol, low density lipoprotein (LDL) cholesterol, or triglycerides, or increase levels of high-density lipoprotein (HDL) cholesterol when compared with placebo or control. However, patients evaluated in the available clinical research include those with type 2 diabetes, metabolic syndrome, coronary artery disease (CAD), schizophrenia, and depression, as well as healthy or mildly overweight individuals (100139).
Hypertension. It is unclear if oral saffron reduces blood pressure; the available research is conflicting. Details: Preliminary clinical research shows that drinking black tea containing saffron 1 gram three times daily for 8 weeks does not reduce blood pressure in patients with diabetes and elevated systolic blood pressure (96669). However, another small clinical study in males with hypertension shows that taking saffron stigma 200 mg daily for 12 weeks seems to reduce blood pressure when compared with no intervention (105618).
Impaired glucose tolerance (prediabetes). It is unclear if oral saffron improves glycemic control in adults with prediabetes. Details: A small clinical study in patients with prediabetes and obesity shows that taking saffron extract 15 mg daily for 2 months modestly reduces fasting blood glucose and glycated hemoglobin (HbA1c) when compared with placebo (103933). It is unclear if this small improvement in glycemic control is maintained after 2 months.
Insomnia. It is unclear if oral saffron is beneficial for reducing sleep problems and improving sleep quality in healthy adults or those with underlying medical conditions. Details: A small clinical study in patients with self-reported sleep problems shows that taking a specific saffron extract (affron, Pharmactive Biotech Products) 14 mg twice daily for 4 weeks reduces insomnia, improves sleep quality, and increases restorative sleep when compared with placebo (103935). Another small clinical study in a similar population shows that taking this same product as 14 mg or 28 mg one hour before bedtime for 4 weeks reduces insomnia and improves sleep quality when compared with placebo, with no observed differences between dosage groups (108908). However, a small clinical study in adults with mild to moderate insomnia and anxiety shows that taking a different saffron extract (Saffr'activ SAF 3C PIM, Comercial Quimica Massó) 15.5 mg daily for 6 weeks improves most sleep quality parameters when compared with baseline, but not when compared with placebo (105624). All studies were funded by the supplement manufacturer, which may limit the validity of these findings. A meta-analysis of clinical research evaluating saffron for sleep in a variety of populations, including healthy patients, those with insomnia or type 2 diabetes, or individuals receiving methadone maintenance treatment, suggests that taking saffron or the constituent crocin improves sleep quality when compared with placebo (108912). Furthermore, a small clinical study in patients with type 2 diabetes with overweight or obesity shows that taking saffron 100 mg daily for 8 weeks improves global Pittsburgh Sleep Quality Index (PSQI) scores when compared with placebo (108905).
Labor pain. Although there is interest in using oral saffron to reduce labor pain, there is insufficient reliable information about the clinical effects of saffron for this purpose.
Male infertility. It is unclear if oral saffron is beneficial for improving sperm parameters in males with infertility. Details: Clinical research in males under 45 years of age with oligoasthenoteratozoospermia shows that taking a saffron extract 30 mg orally twice daily for 26 weeks does not increase sperm motility, density, or morphology when compared with placebo (18102). Other preliminary clinical research in males with idiopathic infertility shows that taking saffron 50 mg three times each week for 3 months improves sperm motility and morphology, but not sperm count, when compared to baseline (19033). These conflicting outcomes may be related to the cause of infertility, as well as the dose and form of saffron used.
Menopausal symptoms. It is unclear if oral saffron reduces menopausal symptoms. Details: A small clinical study in patients with menopausal symptoms shows that taking a specific saffron stigma extract (affron, Pharmactive Biotech Products) 14 mg twice daily for 12 weeks improves symptoms of depression and anxiety, but not vasomotor symptoms such as hot flashes, when compared with placebo (105622). Saffron has also been evaluated in combination with other ingredients. A small clinical study in patients with menopausal symptoms shows that taking a combination of saffron 60 mg, fennel 120 mg, and chamomile 1000 mg daily for 12 weeks modestly reduces physical, psychological, and urogenital symptom scores on the Menopause Rating Scale when compared with either placebo or lower doses of this combination (103628). The validity of this study is limited by unclear reporting of results. Also, it is unclear if reported benefits are due to saffron, other ingredients, or the combination.
Multiple sclerosis-related fatigue. It is unclear if oral saffron reduces symptoms of fatigue in patients with multiple sclerosis. Details: A small clinical study in patients with MS shows that taking one tablespoon of simple syrup containing saffron extract 0.5% every 8 hours for two months reduces fatigue when compared with baseline (103930). The validity of this finding is limited by the lack of a comparator group.
Obsessive-compulsive disorder (OCD). It is unclear if oral saffron reduces symptoms of opioid withdrawal. Details: A small clinical study in adults with OCD shows that taking crocin, a constituent of saffron, 15 mg daily for 8 weeks reduces symptoms when compared with baseline, but is no better than fluoxetine 20 mg daily (105620). This finding is limited due to small study size and the subjectivity of outcome measures.
Opioid withdrawal. It is unclear if oral saffron is beneficial for opioid withdrawal; the available research is conflicting. Details: A small clinical study in adults receiving treatment with methadone for opioid abuse shows that taking crocin, a constituent of saffron, 30 mg daily for 12 weeks modestly reduces cravings and withdrawal symptoms when compared with placebo (105616). Conversely, a small clinical study in patients with opioid dependence shows that taking a specific product (Krocina) containing crocin, a constituent of saffron, 15 mg twice daily for 6 weeks in addition to motivational counseling does not improve withdrawal symptoms, cravings, depression, anxiety, or stress during the detoxification or abstinence phase (108913). The reason for these conflicting findings is unclear but may be related to the differences in adjunctive treatments between studies.
Postpartum depression. It is unclear if oral saffron is beneficial for speeding recovery from postpartum depression. Details: Preliminary clinical research in patients experiencing symptoms of depression less than 12 weeks after giving birth shows that taking saffron 30 mg daily for 6 weeks (SaffroMood, Green Plants of Life Co. Ltd) is as effective as fluoxetine for treating depression. Both treatment groups experienced similar remission and partial response rates (93402). Another preliminary study in breastfeeding Iranian patients with mild to moderate depression shows that taking saffron 15 mg twice daily for 8 weeks improves depressive symptoms by about 50% when compared to baseline (97361). However, it is not clear if the improvement in these studies was related to saffron or the natural resolution of postpartum depression.
Premenstrual dysphoric disorder (PMDD). It is unclear if oral saffron improves PMDD symptoms. Details: A clinical study in patients with PMDD shows that taking saffron 15 mg twice daily for 14 days prior to menstruation improves patient-rated PMDD symptom severity when compared with placebo, but not when compared with taking fluoxetine 20 mg twice daily (105625).
Premenstrual syndrome (PMS). It is unclear if oral saffron improves PMS symptoms. Details: A small clinical study in patients aged 20-45 years with PMS shows that taking a specific saffron extract 15 mg twice daily throughout two menstrual cycles improves symptom severity when compared with placebo (16555).
Psoriasis. Although there is interest in using oral saffron for psoriasis, there is insufficient reliable information about the clinical effects of saffron for this condition.
Rheumatoid arthritis (RA). It is unclear if oral saffron reduces RA symptoms. Details: A small clinical study in females with RA shows that taking saffron 100 mg daily for 3 months modestly reduces the number of tender and swollen joints and reduces pain when compared with placebo (103932). The validity of this study is limited by its small size and the fact that all clinical parameters were secondary, exploratory outcomes. In contrast, a small clinical study in patients with newly diagnosed RA shows that adding saffron 100 mg daily for 3 months to standard treatment with prednisolone 5 mg daily and methotrexate 7.5 mg once weekly does not improve disease activity or quality of life when compared with placebo and standard treatment (108907). The validity of this finding is limited due to low adherence to treatment protocols.
Ulcerative colitis. It is unclear if oral saffron reduces ulcerative colitis symptoms. Details: A small clinical study in patients with ulcerative colitis shows that taking saffron extract 100 mg daily for 8 weeks reduces disease activity when compared with placebo (105626). More evidence is needed to rate saffron for these uses.

ZEAXANTHIN

POSSIBLY EFFECTIVE

Age-related macular degeneration (AMD). Oral zeaxanthin, when used in low levels as part of multi-ingredient products containing lutein, seems to improve some aspects of vision in patient with AMD. It is unclear if oral zeaxanthin alone or in amounts similar to lutein is beneficial for slowing AMD progression. Details: Epidemiological research has found that people who consume higher amounts of zeaxanthin plus lutein in the diet have a reduced risk of developing late AMD, but not early or intermediate AMD (60238,106353,106359). However, any association between intake of zeaxanthin itself and the development of AMD is not clear. Some clinical research has assessed whether zeaxanthin alone can reduce symptoms and progression of AMD. A small clinical trial shows that taking supplemental zeaxanthin 8 mg daily for 12 months modestly improves some aspects of vision, such as macular pigment optical density, the ability to see details of near objects (near vision acuity), and resolution of scotoma (blind spot), when compared with placebo in patients with AMD (60245). Other clinical research in a healthy population shows that taking zeaxanthin alone (Optisharp) as 10 mg daily for 6-12 months increases macular pigment optical density (60175). Most clinical research in patients with AMD has assessed zeaxanthin in combination with lutein. In general, this combination has been shown to increase macular pigment optical density, as well as the ability to see under low-contrast conditions (contrast sensitivity) and visual acuity. However, most research has used much higher doses of lutein compared with zeaxanthin (60281,91160,97225,106366,108615). Use of near equal amounts, such as zeaxanthin 8-10 mg daily plus lutein 9-10 mg daily for up to 2 years, seems to improve macular density in adults with or without AMD (60175,60268,60270,106358); however, effects on vision when used for up to 2 years in patients with AMD are conflicting (60245,60268,60270,106358). Zeaxanthin has also been evaluated in combination with other ingredients, with conflicting findings. A specific supplement (AZYR SIFI) containing zeaxanthin 1 mg, lutein 10 mg, vitamin C 180 mg, vitamin E 30 mg, zinc 22.5 mg, copper 1 mg, and astaxanthin 4 mg has been used daily for 1-2 years with moderate evidence of benefit (19196,60244). Taking zeaxanthin 2 mg plus lutein 10 mg in addition to the original Age-Related Eye Disease Study (AREDS) formulation (vitamins C and E, beta-carotene, and zinc) does not seem to prevent the progression to advanced AMD more than the AREDS formulation alone. However, this progression was modestly inhibited in individuals with low dietary intakes of lutein and zeaxanthin. While progression to late AMD was only modestly inhibited at 5 years when these doses of lutein and zeaxanthin were included in a revised formulation devoid of beta-carotene (60281), results of an additional 5 years of follow up showed that this revised formulation reduces the risk of progression to late AMD by 15% when compared with the formulation containing beta-carotene (108615). Clinical research shows that adding meso-zeaxanthin 10 mg to this revised AREDS formulation (AREDS2) does not further improve contrast sensitivity in patients with non-advanced AMD (106369). In first-generation offspring of parents with neovascular AMD, taking zeaxanthin 2 mg, lutein 10 mg, vitamin C 180 mg, vitamin E 30 mg, zinc 15 mg, and copper 1 mg daily for 6 months does not improve the macular pigment optical density (106347). Reasons for these discrepancies are not clear but may relate to the patient population, zeaxanthin dose, treatment duration, or other ingredients included in combination products.

Age-related cognitive decline. It is unclear if oral zeaxanthin is beneficial for attenuating cognitive decline in older adults. Details: Clinical research in adults 40-75 years old shows that taking zeaxanthin 2 mg with lutein 10 mg daily for 6 months improves some, but not all, measures of visual memory when compared with placebo. However, other measures of memory and cognitive function were not improved (109763). Also, preliminary clinical research in older adults shows that taking the same dose of zeaxanthin and lutein for one year modestly improves some measures of cognitive function, such as complex attention and cognitive flexibility, when compared with placebo (106367). Some observational research in patients 50 years and older has found that higher dietary lutein and zeaxanthin intake is associated with greater word recall when compared with lower intake (102891). However, clinical research in patients over 60 years old shows that taking zeaxanthin 2 mg with lutein 10 mg daily for 5 years in addition to vitamins C and E, beta-carotene, and zinc (AREDS) does not improve markers of cognitive function, such as memory and verbal fluency, when compared with AREDS alone (94702).
Alzheimer disease. Oral zeaxanthin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with mild to moderate Alzheimer disease shows that taking zeaxanthin 2 mg, lutein 10 mg, meso-zeaxanthin 10 mg, fish oil 1 gram (providing docosahexaenoic acid 500 mg and eicosapentaenoic acid 150 mg), and vitamin E 15 mg (Memory Health) daily for 12 months does not affect disease severity when compared with placebo. However, there were modest increases in the number of patients experiencing either an improvement or attenuated decline in memory and mood (109764). The effect of zeaxanthin alone is unclear.
Asthenopia (eye strain). Oral zeaxanthin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Results from one clinical trial show that taking a combination product (Cerebos Pacific Limited) containing zeaxanthin 1 mg, lutein 5 mg, and black currant extract 200 mg daily for 2 weeks modestly improves visual fatigue and eye stress when compared with placebo in patients completing a two-hour visual proof reading task (60214). The effect of zeaxanthin alone on eye strain is unclear.
Asthma. It is unclear if oral zeaxanthin is beneficial for asthma prevention. Details: Population research has found that a higher dietary intake of zeaxanthin plus lutein is associated with up to 30% lower odds of having asthma when compared with a lower dietary intake (109765). The effects of zeaxanthin intake alone or zeaxanthin supplementation are unclear.
Breast cancer. It is unclear if oral zeaxanthin is beneficial for breast cancer prevention. Details: Epidemiological research has found that higher serum levels of lutein plus zeaxanthin are associated with a reduced risk of developing breast cancer (10132). The effects of supplemental zeaxanthin are unclear.
Bronchopulmonary dysplasia. Oral zeaxanthin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that giving preterm and low birth weight infants a specific product (LUTEINofta, SOOFT Italia SpA) containing zeaxanthin 0.0006 mg and lutein 0.14 mg orally once daily, starting at birth and continuing until 36 weeks' corrected gestational age, does not decrease the incidence of bronchopulmonary dysplasia when compared with placebo (91163). The effect of zeaxanthin alone is unclear.
Cardiovascular disease (CVD). Oral zeaxanthin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in adults 50-85 years old shows that taking lutein 10 mg plus zeaxanthin 2 mg daily for an average of 4.8 years does not decrease the risk of CVD-related mortality or cardiovascular events such as stroke, myocardial infarction, or angina when compared with no supplementation (94701). Individual cardiovascular outcomes were not separately evaluated in this study. The effect of zeaxanthin alone on CVD prevention is unknown.
Cataracts. Increased levels of zeaxanthin in the blood seems to reduce the odds of developing cataracts. It is unclear if dietary or supplemental zeaxanthin is beneficial for cataract treatment or prevention. Details: Some population research has found that higher blood levels of zeaxanthin are associated with a 30% lower odds of developing age-related cataracts, and more specifically, a 37% decreased risk of developing nuclear cataracts (90944,91161). Population research has also found that higher dietary combined intake of lutein plus zeaxanthin is associated with lower odds of developing cataracts. However, any association between intake of zeaxanthin itself and the development of cataracts is unclear (91162). Clinical research shows that taking zeaxanthin 2 mg and lutein 10 mg daily orally, in addition to the Age-Related Eye Disease Study (AREDS) formulation containing vitamin C 500 mg, vitamin E 400 IU, beta-carotene 15 mg, zinc 80 mg, and copper 2 mg, for an average of 4.7 years decreases the risk of needing cataract surgery by 32% when compared with the AREDS formulation alone in patients with low dietary intake of lutein and zeaxanthin, but not in those with higher dietary intake of lutein and zeaxanthin (94703).
Child development. It is unclear if oral zeaxanthin is beneficial for child development. Details: Epidemiological research has found that a higher dietary intake of zeaxanthin in the first and second trimesters of pregnancy is associated with increased verbal intelligence and improved behavior in the child at 6-10 years of age. However, the ability to discriminate between a novel or familiar visual stimulus was reduced at about 6 months of age, and there were no effects on most cognitive outcomes in children aged 3-6 years (107106). Other epidemiological research has found that a higher dietary intake of zeaxanthin plus lutein in children aged 3-6 years may be associated with modestly improved executive function at 6-11 years. However, there were no effects on most cognitive outcomes in children aged 3-6 years or 6-11 years (109761).
Cognitive function. Oral zeaxanthin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in younger adults shows that taking zeaxanthin 2 mg and lutein 10 mg for one year modestly improves some measures of cognitive function, such as spatial memory, when compared with placebo (106348). Observational research has found that intake of choline and lutein plus zeaxanthin is positively associated with cognitive flexibility task performance speed. However, this association is not present with the intake of lutein plus zeaxanthin in the absence of choline (106354). The effect of zeaxanthin alone is unclear.
Colorectal cancer. It is unclear if oral zeaxanthin is beneficial for colorectal cancer prevention. Details: Although some individual epidemiological research disagrees (3962), most research has found that dietary intake of lutein plus zeaxanthin is not associated with a reduced risk of developing colorectal cancer (34481,106372). However, any association with intake of zeaxanthin alone, as supplements or in the diet, is unclear.
Diabetes. Observational research suggests that oral zeaxanthin may not be beneficial for the prevention of diabetes or diabetic complications. Details: Some epidemiological research has found that low serum levels of carotenoids, including zeaxanthin and lutein, are associated with impaired glucose tolerance (60161). Other population research has found that increased dietary intake of zeaxanthin plus lutein does not decrease the risk of developing type 2 diabetes (14004,97227). Other epidemiological research in patients with type 2 diabetes has found that an increased serum concentration of zeaxanthin is not associated with reduced cardiovascular mortality over 14 years (109768).
Esophageal cancer. It is unclear if oral zeaxanthin is beneficial for esophageal cancer prevention. Details: Population research has found that people who consume higher combined amounts of zeaxanthin and lutein in the diet have a 29% lower risk of developing esophageal squamous cell cancer when compared with lower intake (91159). The effects of supplemental zeaxanthin are unclear.
Fractures. It is unclear if oral zeaxanthin is beneficial for fracture prevention. Details: A meta-analysis of observational research has found that increased dietary intake of zeaxanthin and/or lutein is not associated with a reduced risk of hip fractures (97228). The effects of supplemental zeaxanthin are unclear.
Gastric cancer. It is unclear if oral zeaxanthin is beneficial for gastric cancer prevention. Details: A meta-analysis of observational research has found that increased dietary intake of lutein and/or zeaxanthin is not associated with a reduced risk of developing gastric cancer (97231). The effects of supplemental zeaxanthin are unclear.
Glaucoma. Oral zeaxanthin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with open-angle glaucoma shows that taking oral zeaxanthin 2 mg, lutein 10 mg, and meso-zeaxanthin 10 mg daily for 18 months increases macular pigment density, but does not affect visual function, when compared with placebo (109756).
Hyperlipidemia. Although there has been interest in using oral zeaxanthin for hyperlipidemia, there is insufficient reliable information about the clinical effects of zeaxanthin for this condition.
Lung cancer. It is unclear if oral zeaxanthin is beneficial for lung cancer prevention. Details: Epidemiological research has found that low serum levels of carotenoids, including zeaxanthin, are associated with an increased risk of lung cancer (12874). However, other epidemiological research has found that higher serum levels of zeaxanthin are not associated with a reduced risk of dying from lung cancer (39690,60160).
Macular telangiectasia type 2. It is unclear if oral zeaxanthin is beneficial for macular telangiectasia type 2. Details: In patients with macular telangiectasia type 2, observational research has found that taking a specific combination of lutein 10 mg, meso-zeaxanthin 10 mg, and zeaxanthin 2 mg (MacuShield; Alliance Pharmaceuticals) for at least 6 months, with an average duration of 15.7 months, was associated with a stabilization of visual acuity. Also, the number and size of cavitations in the macula were reduced (106355).
Metabolic syndrome. Oral zeaxanthin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Population research in females shows that the highest dietary intake of zeaxanthin plus lutein is associated with 54% reduced odds of developing metabolic syndrome when compared with the lowest intake. However, when supplements containing zeaxanthin plus lutein were included in the total intake, there was no association with metabolic syndrome (109760).
Necrotizing enterocolitis (NEC). Oral zeaxanthin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that giving preterm and low birth weight infants a specific product (LUTEINofta, SOOFT Italia SpA) containing zeaxanthin 0.0006 mg and lutein 0.14 mg orally once daily, starting at birth and continuing until 36 weeks' corrected gestational age, does not decrease the incidence of NEC when compared with placebo (91163).
Non-Hodgkin lymphoma. It is unclear if oral zeaxanthin is beneficial for non-Hodgkin lymphoma prevention. Details: A meta-analysis of observational research has found that increased intake of zeaxanthin/lutein in the diet is associated with an 18% lower risk of developing non-Hodgkin lymphoma when compared with low dietary intake. However, no dose-response relationship was reported (97229). It is unknown if supplemental zeaxanthin has any effect on non-Hodgkin lymphoma risk.
Pancreatic cancer. It is unclear if oral zeaxanthin is beneficial for pancreatic cancer prevention. Details: A meta-analysis of population research has found that increased dietary intake of zeaxanthin and/or lutein is not associated with a reduced risk of pancreatic cancer (97230). The effects of supplemental zeaxanthin are unclear.
Parkinson disease. It is unclear if oral zeaxanthin is beneficial for Parkinson disease prevention. Details: Population research has found that people who consume higher amounts of zeaxanthin in the diet do not have a lower risk of developing Parkinson disease (91164). The effects of supplemental zeaxanthin are unclear.
Pre-eclampsia. It is unclear if oral zeaxanthin is beneficial for the prevention of pre-eclampsia. Details: Some epidemiological research has found that the highest intake of lutein plus zeaxanthin during pregnancy is associated with 68% reduced odds of having pre-eclampsia when compared with the lowest intake (109762). The effects of zeaxanthin supplements are unclear.
Prostate cancer. It is unclear if oral zeaxanthin is beneficial for prostate cancer prevention. Details: Epidemiological research has found that low serum levels of carotenoids, including zeaxanthin, are not associated with an increased risk of prostate cancer (12874). The effects of supplemental zeaxanthin are unclear.
Respiratory tract infections. It is unclear if oral zeaxanthin is beneficial for the treatment or prevention of respiratory tract infections. Details: Epidemiological research has found that high serum levels of zeaxanthin are not associated with decreased incidence or severity of respiratory tract infections in the elderly (60152). The effects of supplemental zeaxanthin are unclear.
Retinopathy of prematurity. Oral zeaxanthin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in preterm and low birth weight infants shows that giving a specific product (LUTEINofta, SOOFT Italia SpA) providing lutein 0.14 mg or 0.5 mg/kg plus zeaxanthin 0.0006 mg or 0.02 mg/kg orally once daily, starting at birth and continuing until 36-40 weeks' corrected gestational age, does not decrease the incidence or severity of retinopathy of prematurity when compared with placebo (60240,60243,91163,102889).
Ulcerative colitis. It is unclear if oral zeaxanthin is beneficial for ulcerative colitis. Details: In patients in the remission phase of ulcerative colitis, observational research has found that a higher dietary intake of lutein plus zeaxanthin is associated with a reduced incidence of constipation, but not flatulence or feelings of urgency (tenesmus) (106362). The effects of supplemental zeaxanthin are unclear.
Visual development. It is unclear if taking oral zeaxanthin during pregnancy can improve the visual acuity of the child. Details: Some observational research has found that the highest maternal plasma zeaxanthin levels at delivery are associated with a 38% lower risk of poor visual acuity in children at 3 years of age when compared with the lowest maternal zeaxanthin levels (102888). However, other epidemiological research has found that dietary intake of zeaxanthin plus lutein during the first or third trimesters of pregnancy is not associated with contrast vision or visual acuity in the child at 11-12 years of age (109759). The effects of zeaxanthin supplements are unclear. More evidence is needed to rate zeaxanthin for these uses.

Safety view details

Below is general information about the safety of the known ingredients contained in the product RBI Vision Performance. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

ASTAXANTHIN

LIKELY SAFE ...when used in amounts found in foods. Astaxanthin has Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when taken orally and appropriately. Astaxanthin 4-18 mg daily has been used with apparent safety for up to 12 weeks. Doses of 40 mg daily have been used with apparent safety for up to 4 weeks (19165,19167,19197,32621,96884,105100).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using in amounts greater than those typically found in foods.

LIKELY SAFE ...when used orally and appropriately. Black currant juice, leaves, and flowers have Generally Recognized As Safe (GRAS) status in the US (4912). Black currant juice up to 3000 mL daily for up to 3 weeks (17636,35987), black currant extracts 1080 mg daily for 8 weeks (17635,93695), and black currant seed oil products up to 10.5 grams daily for 24 weeks (4016,17634,17638,35990) have also been used safely in clinical research. There is insufficient reliable information about the safety of black currant when used topically.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

LUTEIN

LIKELY SAFE ...when used orally and appropriately. Consuming up to 20 mg of lutein daily from both dietary and supplemental sources appears to be safe (3219,3220,60167). Lutein supplements have been safely used in clinical trials at doses of up to 20 mg daily for up to 10 years (11798,60133,60177,94703,94701,100986,104570,107107,108615,109763).

CHILDREN: LIKELY SAFE
when used orally and appropriately. A specific product containing lutein (LUTEINofta, SOOFT Italia SpA) has been used with apparent safety in infants at a dose of 0.14 mg daily for 36 weeks (91163).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately in amounts found in foods. The high end of dietary lutein intake ranges from 6.9-11.7 mg/day (3219,3220).

SAFFRON

LIKELY SAFE ...when used orally in amounts commonly found in foods. Saffron has Generally Recognized as Safe (GRAS) status in the US for use as a spice or food coloring agent (4912).

POSSIBLY SAFE ...when used orally and appropriately in larger amounts, short-term. Saffron extracts have been used with apparent safety in clinical trials at doses of up to 100 mg daily for up to 26 weeks (11024,13103,16555,17214,17401,18102,93395,93397,93400,93403)(93407,97359,99436,100135,100138,100140,100658,100659). The saffron constituent crocin has been used with apparent safety at a dose of up to 30 mg daily for up to 3 months (93410,100139,105616).

POSSIBLY UNSAFE ...when used orally in high doses or for longer than 26 weeks. Taking 5 grams or more of saffron can cause severe side effects. Doses of 12-20 grams can be lethal (12,18). There is insufficient reliable information available about the safety of saffron when used topically.

PREGNANCY: LIKELY UNSAFE
when used orally in amounts exceeding those commonly found in foods. Larger amounts of saffron have uterine stimulant and abortifacient effects (18); avoid using.

LACTATION:
Insufficient reliable information available; avoid using.

ZEAXANTHIN

LIKELY SAFE ...when used orally and appropriately in doses of up to 2 mg daily. Zeaxanthin supplements have been safely used in clinical trials at doses of up to 2 mg daily for up to 10 years (94701,94702,94703,108615).

POSSIBLY SAFE ...when used orally and appropriately in amounts greater than 2 mg daily. Zeaxanthin supplements in doses of 8-10 mg daily for up to 12 months have been used with apparent safety in clinical trials (60175,60245).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately. A specific product containing zeaxanthin (LUTEINofta, SOOFT Italia SpA) has been used with apparent safety in infants at a dose of 0.0006 mg daily for 36 weeks (91163). There is insufficient reliable information available about the safety of zeaxanthin at higher doses or in older children.

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately in amounts found in foods. Zeaxanthin is found in breast milk and levels correlate with infant status (106365). There is insufficient reliable information available about the safety of supplemental zeaxanthin.

Interactions with Drugs view details

Below is general information about the interactions of the known ingredients contained in the product RBI Vision Performance. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

ASTAXANTHIN

CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, astaxanthin may decrease levels of drugs metabolized by CYP2B6.

Details

In vitro research shows that astaxanthin induces cytochrome CYP2B6 enzyme activity in human hepatocytes (32613). This effect has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, astaxanthin may decrease levels of drugs metabolized by CYP3A4.

Details

In vitro research shows that astaxanthin induces CYP3A4 enzyme activity in human hepatocytes (32613). This effect has not been reported in humans.

ANTICOAGULANT/ANTIPLATELET DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, black currant seed oil might increase the risk of bleeding if used in combination with anticoagulant or antiplatelet drugs.

Details

Gamma-linolenic acid (GLA), a constituent of black currant seed oil, appears to have antiplatelet effects (1979,35995).

PHENOTHIAZINES

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, black currant seed oil might increase the risk of seizure in patients receiving phenothiazines.

Details

Black currant seed oil contains gamma-linolenic acid (GLA). There is some concern that taking supplements containing GLA might cause seizures, or lower the seizure threshold, when taken with phenothiazines, although there is no evidence that black currant seed oil causes seizures (88187). In one report, three patients with schizophrenia who had received phenothiazines developed EEG changes suggestive of temporal lobe epilepsy after starting treatment with GLA, although none experienced an actual seizure (21013). In another report, two patients with schizophrenia who were stabilized on phenothiazines developed seizures when evening primrose 4 grams daily, which contains GLA, was added. One of these patients had a prior history of seizures (21010).

LUTEIN

None known.

SAFFRON

ANTIDIABETES DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = B

Theoretically, concomitant use of saffron with antidiabetes drugs might increase the risk of hypoglycemia.

Details

Some clinical research shows that taking saffron extract reduces fasting levels of glucose when used in addition to hypoglycemic agents (100138). However, saffron powder itself has not been shown to reduce fasting glucose levels (99436).

ANTIHYPERTENSIVE DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, concomitant use of saffron with antihypertensive drugs might have additive effects.

Details

Animal and human research suggests that saffron extract can decrease blood pressure (72518,72365,72473,93409).

CAFFEINE

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = B

Theoretically, saffron might inhibit the metabolism of caffeine.

Details

A small clinical study suggests that taking saffron powder 300 mg in 150 mL water daily for 5 days and then taking caffeine 200 mg seems to reduce caffeine metabolite levels in the saliva and urine in males, but not females. Theoretically, this may be due to the inhibition of cytochrome P450 1A2 by saffron (100130).

CNS DEPRESSANTS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, concomitant use of saffron and CNS depressants might have additive sedative effects.

Details

Clinical research shows that taking saffron extract 60 mg orally daily for 26 weeks can cause drowsiness and sedation (18102). Animal research suggests that adding saffron to hexobarbital further increases sleeping and slows motor activity (72544).

ZEAXANTHIN

ANTIDIABETES DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, taking zeaxanthin with antidiabetes drugs might increase the risk of hypoglycemia.

Details

In an animal diabetic model, zeaxanthin has hypoglycemic effects (106363). However, population research has found that increasing intake of dietary zeaxanthin plus lutein does not decrease the risk of developing type 2 diabetes (14004,97227).

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Adverse Effects view details

Below is general information about the adverse effects of the known ingredients contained in the product RBI Vision Performance. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

ASTAXANTHIN

General ...Orally, astaxanthin seems to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, diarrhea, red fecal color.

Gastrointestinal ...Orally, astaxanthin 6 mg daily has caused two cases of increased bowel movements and two cases of red fecal color (91736). A higher dose of astaxanthin (AstaCarox, AstaReal AB) 40 mg daily has caused severe stomach/abdominal pain in two patients (19165).

Ocular/Otic ...Canthaxanthin, another carotenoid substance that is chemically related to astaxanthin, has caused crystals in the retina and loss of visual acuity in one patient (8455). This effect has not been observed with astaxanthin, but patients who have visual changes while taking astaxanthin should stop taking it immediately.

General ...Orally, black currant is generally well-tolerated. Topically, there is a limited amount of information on the adverse effects of black currant.

Gastrointestinal ...Of 2154 patients with hyperlipidemia taking black currant seed oil 1. 8 grams twice daily for 6 weeks, 8 reports of mild diarrhea were considered related to the supplement. These adverse reactions were reported 2-10 days after beginning treatment with black currant seed oil (17638).

LUTEIN

General ...Orally, dietary and supplemental lutein is generally well tolerated. Doses up to 20 mg daily have not resulted in adverse effects.

SAFFRON

General ...Orally, saffron extract seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal complaints, nausea, sedation, vomiting.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis.

Dermatologic ...Orally, sweating and flushing have been reported in clinical research for patients taking saffron 30-60 mg daily (93402,93409). Saffron poisoning can occur with oral intake of doses of 5 grams or more and symptoms include yellow appearance of the skin (2,11).

Gastrointestinal ...Orally, saffron has been associated with changes in appetite, nausea, and vomiting when given at doses of 30 mg twice daily for 26 weeks, or when the saffron constituent crocin was given as 15 mg twice daily for 12 weeks (18102,105616). At lower doses of 30 mg daily, the occurrence rate of these and other adverse events such as dry mouth, dyspepsia, diarrhea, and constipation was rare or similar to placebo (13103,93395,93402,93409). Saffron poisoning can occur with oral intake of doses of 5 grams or more and symptoms include yellow appearance of the mucous membranes (mimicking icterus), vomiting, and bloody diarrhea (2,11).

Genitourinary ...One report of excessive uterine bleeding occurred in a clinical trial. The patient was taking the saffron constituent crocin 15 mg twice daily. It is unclear whether this event was related to treatment with the saffron constituent (93410).
Saffron poisoning can occur with oral intake of doses of 5 grams or more; symptoms include bleeding from the uterus (2,11).

Hematologic ...Orally, saffron extract has been reported to cause decreases in platelet, white blood cell, and red blood cell counts after 7 days to 12 weeks of use with doses of 60-200 mg daily. Many of these decreases were only significant when compared to baseline but did not maintain significance when compared to placebo. These reductions were not considered clinically significant (18102,72473,93403,93409).
Saffron poisoning can occur with oral intake of doses of 5 grams or more; symptoms include bloody diarrhea, hematuria, bleeding from the nose, lips, eyelids or uterus, and thrombocytopenic purpura (2,11).

Immunologic ...Allergy to oral saffron has been reported in clinical trials (93404). Anaphylactic reactions can occur within minutes of eating food prepared with saffron (4107,72555). Occupational exposure to saffron has been associated with the development of rhinoconjunctivitis and allergy-induced asthma (4106).

Neurologic/CNS ...Orally, saffron has been reported to cause drowsiness, headache, agitation, and sedation when given at doses of 30 mg twice daily for up to 26 weeks or when crocin is given as 15 mg twice daily for 12 weeks (18102,105616). At doses of 30 mg daily for 6 weeks, the side effect occurrence rate was similar to placebo (13103). Saffron poisoning can occur with oral intake of doses of 5 grams or more; symptoms include vertigo and numbness (2,11).

Ocular/Otic ...Orally, saffron poisoning with oral intake of doses of 5 grams or more can cause ocular symptoms such as yellow appearance of the sclera (2,11).

Psychiatric ...Orally, saffron has been reported to cause anxiety and hypomania when given at doses of 30 mg twice daily for 26 weeks (18102). At doses of 30 mg daily for 6 weeks, the occurrence rate was similar to placebo (13103,93395). One report of agitation occurred in a clinical trial. The patient was taking the saffron constituent crocin 15 mg twice daily. It is unclear whether this event was related to treatment with the saffron constituent (93410).

Renal ...Orally, the saffron constituent crocin given as 15 mg twice daily for 12 week was associated with one case of urinary incontinence (105616). Saffron poisoning can occur with oral intake of doses of 5 grams or more; symptoms include hematuria and uremic collapse (2,11).

ZEAXANTHIN

General ...Orally, dietary and supplemental zeaxanthin are generally well tolerated. No adverse effects have been reported in clinical research.

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