Phyto-Gen Ocu-gen [Discontinued] by Genestra Brands

POSSIBLY INEFFECTIVE

• Night vision. Most research suggests that oral bilberry does not improve night vision in healthy individuals. Details: There is contradictory evidence about the effectiveness of bilberry for improving night vision; however, much of the research is of poor quality. In general, the most rigorous research shows that bilberry is not effective for improving night vision in healthy individuals (8139,9739,14280,35446). Whether bilberry can improve night vision in patients with night blindness is unclear.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. Oral bilberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study of elderly Norwegian males with subjective cognitive impairment shows that drinking 330 mL of bilberry and red grape juice twice daily for 9 weeks does not improve measures of memory or motor skills when compared with placebo (110641).
• Age-related macular degeneration (AMD). Although there has been interest in using oral bilberry for AMD, there is insufficient reliable information about the clinical effects of bilberry for this purpose.
• Asthenopia (eye strain). Small clinical studies suggest that oral bilberry fruit extract may improve objective measures of asthenopia, but it is unclear if oral bilberry improves subjective symptoms of asthenopia. Details: Two small clinical studies in adults who report general eye strain or those who look at computer or other display screens at work for long periods of time show that taking bilberry-derived anthocyanins 43.2 mg daily for 6 weeks or bilberry extract 240 mg daily for 12 weeks improves objective measures of eye strain after staring at computer screens when compared with placebo (103190,104195). However, bilberry extract did not improve subjective measures of eye strain in the study that evaluated these outcomes (104195). This study may have been underpowered to detect significant differences between groups. Bilberry has also been evaluated in combination with other ingredients for improving eye strain. A small clinical trial in patients with eye strain shows that a combination of fish oil, lutein, and bilberry extract containing bilberry anthocyanidins 59 mg, taken daily for 4 weeks, reduces dry eye, lower back pain, shoulder stiffness, and stuffy head when compared with placebo (35470). It is unclear if these effects are due to bilberry, other ingredients, or the combination.
• Atherosclerosis. Although there has been interest in using oral bilberry for atherosclerosis, there is insufficient reliable information about the clinical effects of bilberry for this purpose.
• Cataracts. Although there has been interest in using oral bilberry for cataracts, there is insufficient reliable information about the clinical effects of bilberry for this purpose.
• Chronic venous insufficiency (CVI). It is unclear if oral bilberry is beneficial in patients with CVI. Details: One small clinical study in patients with CVI shows that taking bilberry extract containing anthocyanins 173 mg daily for 30 days reduces symptoms of CVI when compared with placebo (35510).
• Diabetes. It is unclear if oral bilberry is beneficial in patients with diabetes. Details: One small clinical trial in patients with type 2 diabetes shows that taking a specific extract of bilberry fruit (Mirtoselect, Indena S.p.A) 470 mg once, prior to taking an oral glucose tolerance test, lowers plasma glucose levels when compared with placebo (91507). However, a small crossover trial in Chinese patients with type 2 diabetes shows that taking bilberry fruit extract 700 mg twice daily for 4 weeks does not improve glycated hemoglobin (HbA1c), body weight, blood pressure, or lipid levels when compared with placebo (104194). The validity of the HbA1c-related findings is limited due to the short study duration.
• Diabetic retinopathy. It is unclear if oral bilberry is beneficial in patients with diabetic retinopathy. Details: One small clinical trial in adults with diabetic and hypertensive retinopathy shows that taking bilberry fruit extract 160 mg daily for 6 months, in addition to standard management, improves edema and measures of retinal circulatory health when compared with standard management alone. Bilberry in the form of a generic, commercially available product appears to produce less dramatic improvements than a branded formulation (Mirtoselect, Indena S.p.A.) containing matching anthocyanin content. This specific product also reduced flow velocity in those with high-flow, diabetic retinopathy when compared with either the generic bilberry extract or standard management alone (97032).
• Dry eye. Oral bilberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with severe dry eye symptoms suggests that taking bilberry extract 600 mg and docosahexaenoic fish oil 240 mg once daily for 3 months may modestly improve measures of tear quality and patient-reported scores for dry eye symptoms when compared with control (112415). However, the validity of these results is limited by the lack of a statistical comparison between groups. Additionally, it is unclear if these effects are due to bilberry, fish oil, or the combination.
• Dysmenorrhea. It is unclear if oral bilberry is beneficial in patients with dysmenorrhea. Details: One small clinical study in patients with dysmenorrhea shows that a specific bilberry product (Tegens) containing bilberry anthocyanoside 160 mg, taken twice daily beginning 3 days prior to menses and continuing for 8 days, reduces pelvic pain, lumbosacral pain, breast pain, nausea, vomiting, and headache when compared with placebo (35512).
• Exercise-induced muscle soreness. It is unclear if oral bilberry is beneficial for reducing exercise-induced muscle soreness. Details: A small clinical study in trained athletes shows that drinking 200 mL of bilberry juice, containing about 744 mg phenols and 80 mg anthocyanins, twice daily for 5 days prior to running a half-marathon modestly worsens muscle soreness immediately after the run when compared with placebo. There was no longer a difference in muscle soreness between groups within 1-2 days after the run (99540).
• Glaucoma. Small clinical studies suggest that oral bilberry fruit extract, when taken with maritime pine extract, may lower intraocular pressure in patients with glaucoma. It is unclear if oral bilberry alone is beneficial in patients with glaucoma. Details: One small, uncontrolled clinical trial in Japanese patients with open-angle glaucoma shows that taking a specific product (Sante Glagenox, Saten Pharmaceutical Co. Ltd.) containing bilberry fruit extract 90 mg and maritime pine extract 40 mg daily for 4 weeks reduces intraocular pressure by 8.7% when compared to baseline (104192). Another small clinical study in patients with high intraocular pressure shows that taking a specific product (Mirtogenol) containing bilberry fruit extract (Mirtoselect, Indena S.p.A.) 80 mg and maritime pine extract (Pycnogenol, Horphag Research) 40 mg twice daily for 6 months lowers intraocular pressure and improves intraocular blood flow when compared with no treatment (35456). It is unclear if these findings are due to bilberry, maritime pine, or the combination. A retrospective chart review of patients with normal tension glaucoma has found that taking bilberry anthocyanin 60 mg twice daily for at least 12 months is associated with improvements in visual function when compared to pretreatment (35472).
• Hemorrhoids. Although there has been interest in using oral bilberry for hemorrhoids, there is insufficient reliable information about the clinical effects of bilberry for this purpose.
• Hyperlipidemia. It is unclear if oral bilberry is beneficial in patients with hyperlipidemia. Details: A small clinical study in adults with hyperlipidemia shows that taking bilberry-derived anthocyanins 320 mg daily for 4 weeks does not improve total cholesterol, low-density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, or triglyceride levels. Further, no improvements in other biomarkers of cardiovascular disease were reported (110640). The validity of this study is limited by its short duration.
• Hypertension. Oral bilberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in adults with hypertension shows that consuming 500 mL of a juice containing bilberry, red grape, and chokeberry, with or without black currant (MANA Blue, TINE SA), daily for 12 weeks does not improve blood pressure when compared with placebo (92371).
• Hypertensive retinopathy. It is unclear if oral bilberry is beneficial in patients with hypertensive retinopathy. Details: One small clinical trial in adults with diabetic and hypertensive retinopathy shows that taking bilberry fruit extract 160 mg daily for 6 months, in addition to standard management, improves edema and measures of retinal circulatory health when compared with standard management alone. Bilberry in the form of a generic, commercially available product appears to produce less dramatic improvements than a branded formulation (Mirtoselect, Indena S.p.A.) containing matching anthocyanin content. This specific product also increased flow velocity for those with ischemic, hypertensive retinopathy when compared with either the generic bilberry extract or standard management alone (97032).
• Impaired glucose tolerance (prediabetes). Oral bilberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with impaired glucose tolerance and two markers of metabolic syndrome shows that consuming a diet high in whole grain products, fatty fish, and bilberries three times daily for 12 weeks reduces levels of plasma glucose when compared to baseline (35468). However, it is unclear if these findings are due to bilberry, another component of the diet, or the combination.
• Irritable bowel syndrome (IBS). Oral bilberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical trial in adults with IBS shows that consuming a formula containing powdered bilberry fruit, aerial agrimony parts, cinnamon quills, and slippery elm bark modestly improves bowel movement frequency and reduces symptoms such as abdominal pain, bloating, flatulence, and straining when compared to baseline (35462). It is unclear if these findings are due to bilberry, other ingredients, or the combination.
• Metabolic syndrome. It is unclear if oral bilberry is beneficial in patients with metabolic syndrome. Details: One small clinical study in patients with metabolic syndrome shows that consuming a diet containing 400 grams of fresh bilberries daily does not affect body weight, glucose metabolism, or lipid metabolism when compared with a control diet (35473).
• Myopia. It is unclear if oral bilberry is beneficial in patients with myopia. Details: One small clinical trial in adults with myopia shows that a specific fermented bilberry fruit extract (Fermented Blueberry, Ajinomoto, Co., Inc.) 200 mg, taken twice daily for 4 weeks, improves night vision as well as the eye's ability to adjust focus when compared with placebo. The amplitude of accommodation was also significantly increased from 4.62 to 5.33 (91505).
• Obesity. It is unclear if oral bilberry is beneficial in patients with obesity. Details: One small clinical study in obese and overweight females shows that consuming 100 grams of frozen, whole bilberries daily for 33-35 days decreases weight and waist circumference when compared to baseline (35463). The validity of these findings is limited by the lack of a comparator group.
• Osteoarthritis. Although there has been interest in using oral bilberry for osteoarthritis, there is insufficient reliable information about the clinical effects of bilberry for this purpose.
• Ulcerative colitis. It is unclear if oral bilberry is beneficial in patients with ulcerative colitis. Details: One small, open-label clinical study in adults with mild-to-moderate ulcerative colitis shows that consuming sieved bilberries and concentrated bilberry juice (Symrise GmbH & Co) 160 grams daily for 6 weeks induces remission in 46% of patients. Furthermore, 91% of patients achieved remission at the end of treatment, and 72% of patients achieved remission at the end of the study (91506). The validity of these findings is limited by the lack of a comparator group.
• Urinary tract infections (UTIs). Although there has been interest in using oral bilberry for UTIs, there is insufficient reliable information about the clinical effects of bilberry for this purpose.
• Varicose veins. Although there has been interest in using oral bilberry for varicose veins, there is insufficient reliable information about the clinical effects of bilberry for this purpose. More evidence is needed to rate bilberry for these uses.

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POSSIBLY EFFECTIVE

• Burns. Topical cream containing sea buckthorn seems to improve burn healing. Details: Clinical research in patients with second-degree burn injuries shows that topical application of sea buckthorn 40% cream once daily reduces healing time by about 4.5 days when compared with a specific cream containing silver sulfadiazine 1% (Flamexin, Sina Daru) (106091).

POSSIBLY INEFFECTIVE

• Atopic dermatitis (eczema). Neither oral nor topical sea buckthorn products seem to be beneficial for atopic dermatitis. Details: Preliminary clinical research shows that taking sea buckthorn seed and pulp oils 5 grams daily orally for 4 months may improve the severity of atopic dermatitis when compared to pretreatment; however, treatment with the same dose of sea buckthorn seed oil does not have this effect, and the effect of sea buckthorn pulp oil does not appear to be significantly different than placebo (74021). Additionally, applying sea buckthorn 10% or 20% cream topically for 4 weeks does not seem to reduce the severity of atopic dermatitis when compared with placebo in patients with mild-to-moderate atopic dermatitis (74091).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Although there is interest in using topical sea buckthorn for acne, there is insufficient reliable information about the clinical effects of sea buckthorn for this condition.
• Aging skin. Although there is interest in using oral or topical sea buckthorn for aging skin, there is insufficient reliable information about the clinical effects of sea buckthorn for this purpose.
• Asthma. Although there is interest in using oral sea buckthorn for asthma, there is insufficient reliable information about the clinical effects of sea buckthorn for this condition.
• Cancer. Although there is interest in using oral sea buckthorn for reducing morbidity related to cancer and side effects related to chemotherapy, there is insufficient reliable information about the clinical effects of sea buckthorn for these uses.
• Cirrhosis. It is unclear if oral sea buckthorn is beneficial for patients with cirrhosis. Details: Preliminary clinical research shows that taking sea buckthorn extract 15 grams three times daily for 6 months might reduce liver enzymes and markers of liver inflammation in patients with cirrhosis when compared with a control group taking vitamin B complex (16694).
• Common cold. It is unclear if oral sea buckthorn is beneficial for preventing or treating the common cold. Details: Clinical research in healthy volunteers shows that consuming sea buckthorn berries 28 grams daily in frozen puree for 90 days does not reduce the risk of developing the common cold or reduce the duration of symptoms of the common cold when compared with placebo (16692).
• Diabetes. Although there is interest in using oral sea buckthorn for diabetes, there is insufficient reliable information about the clinical effects of sea buckthorn for this condition.
• Dry eye. It is unclear if oral or topical sea buckthorn is beneficial for dry eye. Details: Preliminary clinical research in adults with dry eye shows that taking a specific sea buckthorn seed and pulp oil product (Omega-7, Aromtech Ltd.) 1 gram orally twice daily for 3 months reduces subjective assessments of eye redness and burning and reduces tear film osmolarity when compared with placebo (17406,74069). Preliminary clinical research also shows that using an eyelid spray containing sea buckthorn seed oil 0.4% and sodium hyaluronate 0.02% (Aromtech Ltd., and Finnsusp Ltd.) four times daily for 1.5 months reduces symptoms of dryness and watering by a small amount when compared to a control spray. However, there was no effect on feelings of grittiness, burning, redness, or other symptoms (102845).
• Dry skin. Although there is interest in using topical sea buckthorn for dry skin, there is insufficient reliable information about the clinical effects of sea buckthorn for this condition.
• Dyslipidemia. It is unclear if oral sea buckthorn is beneficial for hyperlipidemia. Details: Some clinical research shows that sea buckthorn berries and extracts can improve the lipid profile in people with hyperlipidemia and/or nonalcoholic fatty liver disease (NAFLD). In a meta-analysis of 11 studies from China and Finland, consuming sea buckthorn berries or extracts for between 12 days and 4 months decreased total cholesterol and low-density lipoprotein (LDL) cholesterol by about 24 mg/dL and triglycerides by about 41 mg/dL and increased high-density lipoprotein (HDL) cholesterol by about 10 mg/dL when compared with baseline or a control group (96555). The sea buckthorn doses and formulations used in these studies were not identified. Additionally, a very small clinical study in females aged 50-61 with hypercholesterolemia shows that drinking sea buckhorn juice (ZAMIO, Ltd) 100% 50 mL daily for 8 weeks modestly improves HDL by about 2 mg/dL and LDL by 10 mg/dL, but does not impact total cholesterol or triglycerides when compared to baseline (112171). However, the validity of these findings is limited by the lack of a comparator group. In contrast, clinical research in patients with hypercholesterolemia shows that taking sea buckthorn puree 30 grams three times daily for 90 days does not improve lipid markers or blood pressure when compared with placebo (106090).
• Dyspepsia. It is unclear if oral sea buckthorn is beneficial for dyspepsia. Details: Preliminary clinical research shows that taking sea buckthorn dry emulsion (prepared with the fruit juice and oil) daily for 8 weeks increases levels of the appetite regulators leptin and neuropeptide Y, which tend to be lower in children with functional dyspepsia; however, sea buckthorn does not appear to improve gastric emptying rates in these patients. Doses were administered according to age: 2.5 grams twice daily for children aged 1-3 years, 5 grams twice daily for children aged 4-6 years old, and 7.5 grams twice daily for children aged 7 years (94800).
• Gout. Although there is interest in using oral sea buckthorn for gout, there is insufficient reliable information about the clinical effects of sea buckthorn for this condition.
• Hypertension. It is unclear if oral sea buckthorn is beneficial for hypertension. Details: A meta-analysis of preliminary clinical research in patients with essential hypertension shows that taking sea buckthorn flavones 10-30 mg three times daily for 1-8 months reduces systolic and diastolic blood pressure to a similar extent as calcium channel blockers and angiotensin converting enzyme (ACE) inhibitors (74090).
• Impaired glucose tolerance (prediabetes). It is unclear if oral sea buckthorn is beneficial for prediabetes. Details: A small clinical trial in patients with impaired glucose tolerance shows that taking sea buckthorn fruit puree 90 mL daily in three divided doses for 5 weeks modestly reduces fasting levels of blood glucose when compared with taking placebo. There was no effect on postprandial glucose levels or blood pressure (106088).
• Kidney failure. It is unclear if oral sea buckthorn oil is beneficial for patients on hemodialysis. Details: Preliminary clinical research shows that taking sea buckthorn oil 2 grams daily for 8 weeks does not improve levels of urea, creatinine, or calcium, reduce markers of inflammation, or improve salivary flow rate when compared with placebo in patients with chronic kidney disease (CKD) who are receiving hemodialysis (94798).
• Melasma. Although there is interest in using topical sea buckthorn for melasma, there is insufficient reliable information about the clinical effects of sea buckthorn for this condition.
• Nephrotic syndrome. It is unclear if oral sea buckthorn is beneficial for nephrotic syndrome. Details: Preliminary clinical research in patients with idiopathic nephrotic syndrome shows that taking hydroalcoholic extract of sea buckthorn 350 mg orally twice daily for 3 months in addition to standard therapy reduces edema, anorexia, and the extent of proteinuria when compared to baseline. It is unclear if the effects of sea buckthorn plus standard therapy are significantly better than the effects of standard therapy alone (94799).
• Obesity. It is unclear if oral sea buckthorn is beneficial for obesity. Details: Preliminary clinical research shows that taking sea buckthorn berries, berry oil, or phenolic alcoholic extract does not reduce body weight in overweight or obese females, although it seems to reduce low-density lipoprotein (LDL) cholesterol (35463,94796).
• Peptic ulcers. Although there is interest in using oral sea buckthorn for peptic ulcers, there is insufficient reliable information about the clinical effects of sea buckthorn for this condition.
• Psoriasis. It is unclear if topical sea buckthorn is beneficial for psoriasis. Details: One small clinical study in patients with previously untreated psoriasis shows that topically applying an unknown amount of sea buckthorn fruit extract suspended in corn oil twice daily for 8 weeks reduces the severity of psoriasis lesions when compared with corn oil alone (102844).
• Radiation dermatitis. Although there is interest in using topical sea buckthorn for radiation dermatitis, there is insufficient reliable information about the clinical effects of sea buckthorn for this condition.
• Rheumatoid arthritis (RA). Although there is interest in using oral sea buckthorn for RA, there is insufficient reliable information about the clinical effects of sea buckthorn for this condition.
• Sunburn. Although there is interest in using topical sea buckthorn for sunburn prevention, there is insufficient reliable information about the clinical effects of sea buckthorn for this condition.
• Vaginal atrophy. It is unclear if oral or intravaginal sea buckthorn is beneficial for vaginal atrophy. Details: Preliminary clinical research shows that taking 3 grams of sea buckthorn oil daily for 3 months does not improve vaginal dryness, itching, burning, pH, or elasticity when compared with placebo in postmenopausal individuals with vaginal atrophy (94797). Topical sea buckthorn oil has also been evaluated, in combination with other ingredients. Clinical research in adults with postmenopausal vulvovaginal atrophy shows that intravaginal application of a specific gel (Meclon Idra Alfasigma, Giellepi) containing sea buckthorn oil, aloe vera, 18-beta-glycyrrhetic acid, hyaluronic acid, and glycogen modestly improves sexual function and reduces vaginal pain, dyspareunia, and symptoms such as vaginal dryness, itching, and burning when compared with a placebo gel. The gel was used daily for 14 days and then twice weekly for 60 days after a 2-week washout (106089). It is unclear if these benefits are due to sea buckthorn oil, other ingredients, or the combination.
• Wound healing. Although there is interest in using topical sea buckthorn for healing of pressure ulcers, skin ulcers, or other wounds, there is insufficient reliable information about the clinical effects of sea buckthorn for this purpose.
• Wrinkled skin. Oral sea buckthorn oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in people with facial photodamage and severe fine wrinkling shows that taking a specific combination product (GliSODin Skin Nutrients Advanced Anti-Aging Formula, Isocell North America Inc.) as one capsule orally three times daily for 90 days, in addition to applying tazarotene 0.1% cream, improves the appearance of wrinkles, hyperpigmentation, and photodamage when compared with using tazarotene 0.1% cream alone. Three capsules of this product contain sea buckthorn berry oil 200 mg, krill oil 600 mg, zinc 10 mg, vitamin D 400 IU, cacao bean extract 100 mg, hyaluronic acid 30 mg, red clover flower isoflavones 30 mg, and a specific proprietary ingredient called GliSODin 500 mg (91778). It is not clear if these effects are due to sea buckthorn, the other ingredients, or the combination. More evidence is needed to rate sea buckthorn for these uses.

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LIKELY SAFE ...when used orally and appropriately in amounts commonly found in foods. Bilberry has Generally Recognized As Safe status (GRAS) for use in foods in the US (4912).

POSSIBLY SAFE ...when used orally and appropriately for medicinal purposes. Bilberry fruit extracts have been used with apparent safety in clinical trials at a dose of up to 160 mg daily for up to 6 months (39,40,8139,9739,14280,35472,35510,35512,103190,104192,104195). A higher bilberry extract dose of 1.4 grams daily has been used with apparent safety for up to 4 weeks (104194). Whole bilberries or bilberry juice have also been consumed with apparent safety in quantities of 100-160 grams daily for up to 35 days (35463,91506).

POSSIBLY UNSAFE ...when the leaves are used orally in high doses or for a prolonged period. Death can occur with chronic use of 1.5 gram/kg daily (2).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in the amounts commonly found in foods. However, there is insufficient reliable information available about the safety of bilberry when used in medicinal amounts during pregnancy and lactation; avoid using.

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LIKELY SAFE ...when sea buckthorn fruit is consumed as food. Sea buckthorn fruit is used in jams, jellies, pies, juices, and sauces (9898).

POSSIBLY SAFE ...when sea buckthorn fruit or fruit extract is used orally and appropriately for medicinal purposes. The oil extract of the fruit and seed have been used with apparent safety in doses of up to 2 grams daily for up to 3 months (16692,17406). ...when sea buckthorn fruit is used topically and appropriately. A cream containing sea buckthorn fruit 40% daily has been used with apparent safety for up to 13 days (106091). There is insufficient reliable information available about the safety of sea buckthorn leaf or leaf extracts when used orally or topically.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately for medicinal purposes. Sea buckthorn dry emulsion (prepared with the fruit juice and oil) 5-15 grams daily for 8 weeks has been used with apparent safety in children 1-7 years of age (94800).

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

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, bilberry fruit extract might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.  Details In vitro, animal, and clinical research suggest that anthocyanidin extracts from bilberry can inhibit platelet aggregation (16631,35455,35503,35504,35505).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, bilberry leaf or fruit extract may increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details Animal research suggests that bilberry leaf extract might have blood glucose-lowering activity (1264). Also, one small clinical trial in patients with type 2 diabetes shows that taking bilberry fruit extract 470 mg as a single dose prior to an oral glucose tolerance test lowers plasma glucose levels when compared with placebo (91507).

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, bilberry fruit extract might decrease levels of drugs metabolized by CYP2E1.  Details Animal research shows that exposure to small concentrations of bilberry extract in drinking water for around one month increased CYP2E1 activity by 31%. However, exposure over a 2-month period did not increase CYP2E1 activity (103191). This effect has not been reported in humans.

ERLOTINIB (Tarceva) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, bilberry fruit extract might reduce the efficacy of erlotinib.  Details In vitro research suggests that bilberry fruit extract and its constituents, delphinidin and delphinidin-3-O-glucoside, inhibit the activity of erlotinib (97031). This interaction has not been reported in humans.

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, sea buckthorn may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details Clinical research suggests that sea buckthorn fruit extracts can inhibit platelet aggregation and adhesion to collagen and fibrinogen (10208,96554).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking sea buckthorn with antihypertensive drugs might increase the risk of hypotension.  Details Taking sea buckthorn appears to reduce blood pressure in some patients (74090).

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General ...Orally, bilberry fruit, juice, and extracts seem to be well tolerated.
Most Common Adverse Effects:
Orally: Dark-colored stools, flatulence, and gastrointestinal discomfort.

Gastrointestinal ...In one small clinical trial, mild-to-moderate flatulence was reported in 33% of patients taking sieved bilberries and concentrated bilberry juice (91506). However, the patients in this study had ulcerative colitis, and the study lacked a control group, limiting the validity of this finding. In another small clinical study of males with age-related cognitive impairment, temporary adverse gastrointestinal (GI) effects were reported in 13% of patients drinking a combination of bilberry and grape juice. However, the adverse GI effect rate was identical in patients drinking a placebo juice (110641). A post-marketing surveillance report of 2295 patients using bilberry extract (Tegens) found that 1% of patients complained of GI discomfort and less than 1% experienced nausea or heartburn (35500).
Theoretically, fresh bilberry fruit may have laxative effects. One clinical trial noted an increased frequency of bowel movements following the administration of a combination formulation containing aerial agrimony parts, cinnamon quills, powdered bilberry fruit, and slippery elm bark (35462). It is unclear if these effects were due to bilberry, other ingredients, or the combination.

Other ...Orally, bilberry may cause discoloration of feces and the tongue. In one study, a dark-bluish to black discoloration of both the feces and the tongue was observed following consumption of sieved bilberries and concentrated bilberry juice. In one patient, a slight discoloration of the teeth has also been observed (91506). In another study, 50% of patients reported dark green stools after taking bilberry extract 700 mg twice daily for 4 weeks (104194).

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General ...Orally, sea buckthorn is well tolerated. Topically, sea buckthorn fruit seems to be well tolerated.
Most Common Adverse Effects:
Topically: Irritation and rash.

Dermatologic ...Orally, high doses of sea buckthorn may cause yellow staining of the skin. One case of generalized yellow skin has been reported for a patient who consumed sea buckthorn 100 grams daily for 6 months (74072). Topically, sea buckthorn oil has been associated with dryness, irritation, redness, and rash (74077,102845). Rash occurred in 4% of patients in one clinical study (74077). When used intravaginally, severe burning and itching have been reported rarely (106089).

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