Norwegian Cod Liver Oil by Pharmetics Inc.

POSSIBLY INEFFECTIVE

• Coronavirus disease 2019 (COVID-19). Oral cod liver oil does not seem to be beneficial for COVID-19 prevention. Details: A large clinical trial in adults shows that taking cod liver oil 5 mL daily for up to 6 months in winter does not prevent any or serious COVID-19 infection compared with placebo. Each 5 mL of cod liver oil provided vitamin D3 400 IU, eicosapentaenoic acid (EPA) 0.4 grams, and docosahexaenoic acid (DHA) 0.5 grams (110378).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related macular degeneration (AMD). It is unclear if oral cod liver oil prevents AMD. Details: A population study from Iceland suggests that taking oral cod liver oil supplements daily is not associated with a reduced risk of developing AMD over a 5-year period when compared to not taking cod liver oil (94753). However, since dietary fish intake is relatively high in this population, additional cod liver oil supplementation may not have been beneficial.
• Allergic rhinitis (hay fever). It is unclear if oral cod liver oil during pregnancy prevents allergic rhinitis in the child. In addition, it is unclear if oral cod liver oil during childhood prevents allergic rhinitis. Details: Population research from Norway found that taking cod liver oil at least once weekly during pregnancy or breast-feeding is not associated with a reduced risk of allergic rhinitis in the child. Also, consumption of cod liver oil at least once weekly at 2 years of age is not associated with a reduced risk of allergic rhinitis at age 6 years (101989). Since the participants in this study normally consumed high amounts of oily fish and cod liver oil, it is unclear if cod liver oil would be beneficial in populations with normally low intake.
• Arrhythmia. It is unclear if oral cod liver oil is beneficial for ventricular premature complexes (VPCs). Details: Preliminary clinical research shows that taking cod liver oil (Möller Tran) 15 mL orally daily for 16 weeks might reduce VPCs in people with moderate to low-grade ventricular arrhythmias and no significant heart failure. Approximately 44% of patients treated with cod liver oil achieved a clinically relevant reduction in VPCs, compared to only 15% taking placebo (7360). However, it is not clear if this reduction in VPCs correlates with a reduction in the risk of cardiovascular-related mortality. Other clinical research shows that taking cod liver oil 20 mL orally daily for 6 weeks does not reduce the number of ventricular extrasystoles or other arrhythmias in men with arrhythmias following myocardial infarction (MI) (94759).
• Asthma. It is unclear if oral cod liver oil during pregnancy or while breast-feeding prevents asthma in the child. In addition, it is unclear if oral cod liver oil during childhood prevents asthma. Details: Population research has found that taking cod liver oil 1-3 times weekly during pregnancy is associated with a 43% reduced risk of asthma in the child at 6 years of age. However, taking cod liver oil at least 4 times weekly during pregnancy, or taking it while breast-feeding, is not associated with a reduced risk of asthma in the child at 6 years of age. Also, consumption of cod liver oil at least once weekly at 2 years of age is not associated with a reduced risk of asthma at age 6 years (101989). Since the participants in this study normally consumed high amounts of oily fish and cod liver oil, it is unclear if cod liver oil would be more beneficial in populations with normally low intake.
• Atopic dermatitis (eczema). It is unclear if oral cod liver oil during pregnancy or while breast-feeding prevents eczema in the child. In addition, it is unclear if oral cod liver oil during childhood prevents eczema. Details: Population research has found that taking cod liver oil at least once weekly during pregnancy or breast-feeding is not associated with a reduced risk of eczema in the child. Also, consumption of cod liver oil at least once weekly at 2 years of age is not associated with a reduced risk of eczema at age 6 years (101989). However, in the infant, taking cod liver oil at least 4 times a week at one year of age is associated with a 29% reduced prevalence of eczema (101989).
• Burns. Although there has been interest in using topical cod liver oil for burns, there is insufficient reliable information about the clinical effects of cod liver oil for this condition.
• Coronary heart disease (CHD). Although there has been interest in using oral cod liver oil for CHD, there is insufficient reliable information about the clinical effects of cod liver oil for this condition.
• Depression. It is unclear if oral cod liver oil prevents depressive symptoms. Details: Evidence from a large population study including Norwegian adults aged 40-49 and 70-74 years shows that taking cod liver oil orally daily is associated with a 29% lower odds of depressive symptoms when compared with not taking cod liver oil (15648).
• Diabetes. It is unclear if oral cod liver oil is beneficial in gestational or type 1 diabetes. Details: In women with gestational diabetes, clinical research shows that taking cod liver oil 500 mg daily for 4 weeks, starting at 24-28 weeks gestation, does not improve levels of glycated hemoglobin (HbA1c), fasting blood glucose, insulin resistance, or plasma lipids when compared with placebo. However, taking cod liver oil for 12-16 weeks reduces HbA1c by 8.4%, fasting blood glucose by 41%, and insulin resistance by 43%, when compared with baseline. These differences were statistically significant when compared with placebo. Taking cod liver oil also resulted in a 17.5% reduction in perinatal complications, especially postpartum infections and Caesarian section (101988). Preliminary clinical research in patients with type 1 diabetes and elevated cholesterol levels shows that taking cod liver oil (Eskisol emulsion, Pharma-Vinci A/s) 21 mL orally daily for 8 weeks does not lower total cholesterol or LDL cholesterol levels, or affect insulin requirement, HbA1c, or blood glucose levels. There was a small effect on high-density lipoprotein (HDL) cholesterol and systolic and diastolic blood pressure (3399).
• Diabetic nephropathy. Although there has been interest in using oral cod liver oil for diabetic nephropathy, there is insufficient reliable information about the clinical effects of cod liver oil for this condition.
• Diaper rash. Although there has been interest in using topical cod liver oil for diaper rash, there is insufficient reliable information about the clinical effects of cod liver oil for this condition.
• Exercise-induced muscle damage. Although there has been interest in using oral cod liver oil for exercise-induced muscle damage, there is insufficient reliable evidence about the clinical effects of cod liver oil for this purpose.
• Familial hypercholesterolemia. It is unclear if oral cod liver oil is beneficial in familial hypercholesterolemia. Details: Preliminary clinical research shows that taking cod liver oil does not lower total cholesterol, low-density lipoprotein (LDL) cholesterol, or triglyceride levels, or increase high-density lipoprotein (HDL) cholesterol levels, in patients with familial type IIa hypercholesteremia when compared to baseline (10083).
• Glaucoma. Although there has been interest in using oral cod liver oil for glaucoma, there is insufficient reliable information about the clinical effects of cod liver oil for this condition.
• Hemorrhoids. Although there has been interest in using topical cod liver oil for hemorrhoids, there is insufficient reliable information about the clinical effects of cod liver oil for this condition.
• Hypercholesterolemia. It is unclear if oral cod liver oil is beneficial for lowering lipid levels; the available research is conflicting. Details: Preliminary clinical research shows that taking cod liver oil (Eskisol emulsion, Pharma-Vinci A/s) 21 mL orally daily for 8 weeks does not lower total cholesterol or low-density lipoprotein (LDL) cholesterol levels in patients with type 1 diabetes and elevated cholesterol levels. However, it appears to increase high-density lipoprotein (HDL) cholesterol levels by 5 mg/dL when compared to baseline (3399). Other clinical research in men with a history of myocardial infarction shows that taking an Icelandic cod liver oil 20 mL orally daily for 6 weeks appears to decrease triglycerides by 18 mg/dL when compared to baseline, with no improvement in LDL cholesterol levels (94758). A large, single-blind clinical study of patients with hypercholesterolemia shows that taking oral cod liver oil 415 mg daily in conjunction with oral rosuvastatin 10 mg daily for 30 days further reduces total cholesterol and LDL cholesterol levels when compared with rosuvastatin monotherapy (107491). It is unclear if this effect is due to cod liver oil, rosuvastatin, or the combination.
• Hypertension. It is unclear if oral cod liver oil is beneficial for lowering blood pressure. Details: In adults with type 1 diabetes, albuminuria, and mild hypertension, taking cod liver oil (Eskisol emulsion, Pharma-Vinci A/s) 21 mL orally daily for 8 weeks can reduce systolic blood pressure by 7 mmHg and diastolic blood pressure by 5 mmHg when compared to baseline (3399). A small clinical study in healthy men shows that taking cod liver oil (British Cod Liver Oils, Hull, UK) 5 mL orally four times daily with meals for 6 weeks can reduce systolic blood pressure by 13 mmHg and diastolic blood pressure by 12 mmHg when compared to baseline (4026). However, the validity of these findings is limited by the lack of comparator groups.
• Hypertriglyceridemia. It is unclear if oral cod liver oil is beneficial for lowering triglyceride levels. Details: Clinical research in men with a history of myocardial infarction shows that taking cod liver oil 20 mL orally daily for 6 weeks appears to decrease triglycerides by 18 mg/dL when compared to baseline, with no improvement in LDL cholesterol levels (94758). The clinical significance of these changes in patients with hypertriglyceridemia are unclear.
• Inflammatory bowel disease (IBD). It is unclear if oral cod liver oil is beneficial in IBD. Details: Preliminary clinical research shows that taking cod liver oil (Möller Axellus AS) 10 mL orally three times daily before meals for 14 days reduces joint pain intensity in adults with arthralgias associated with Crohn disease or ulcerative colitis when compared to baseline (94754). The validity of this finding is limited by the lack of a comparator group.
• Myocardial infarction (MI). It is unclear if oral cod liver oil is beneficial for preventing MI. Details: A large, non-blinded clinical study in patients at moderate to high risk for a cardiovascular event shows that taking oral cod liver oil 415 mg daily for up to 12 months does not affect the overall incidence of MI or the incidence of fatal or non-fatal MI when compared with no supplementation (107490). It is unclear if cod liver oil supplementation has any effect on modifiable risk factors such as hypertension and hypercholesteremia, which may impact the long-term incidence of MI.
• Osteoarthritis. It is unclear if oral cod liver oil is beneficial when used with nonsteroidal anti-inflammatory drugs (NSAIDs). Details: Preliminary clinical research shows that taking cod liver oil 10 mL orally daily for 24 weeks, in combination with NSAIDs, does not decrease pain or inflammation when compared with NSAID treatment alone (3398).
• Otitis media. It is unclear if oral cod liver oil prevents otitis media in children. Details: Preliminary clinical research shows that taking cod liver oil 5 mL orally daily, in combination with a children's multivitamin-mineral preparation containing selenium, can reduce the number of days of antibiotic therapy in an otitis media (OM) season in young children aged 0.8-4.4 years. The mean percentage of days on antibiotics in the OM season decreased by 12% when compared with the previous year's OM season, when no supplements were used (10151).
• Respiratory tract infections. It is unclear if oral cod liver oil prevents respiratory tract infections. Details: A large clinical trial in adults shows that taking cod liver oil 5 mL daily for up to 6 months in winter does not prevent acute respiratory infections compared with placebo. Each 5 mL of cod liver oil provided vitamin D3 400 IU, eicosapentaenoic acid (EPA) 0.4 grams, and docosahexaenoic acid (DHA) 0.5 grams (110378). However, preliminary clinical research shows that giving children a specific cod liver oil product (Carlson for Kids cod liver oil lemon flavor, Carlson Labs) along with a multivitamin (Carlson for Kids Scooter Rabbit Chewable Vitamins and Minerals, Carlson Labs) for about 5 months decreases the number of doctor's office visits for respiratory tract infections when compared with no supplementation. Children aged 1-5 years received 1 teaspoon of cod liver oil and half a multivitamin tablet daily; children aged 0.5-1 year received half doses (94756).
• Rheumatoid arthritis (RA). It is unclear if oral cod liver oil is beneficial in RA. Details: A preliminary, uncontrolled study suggests that taking a specific cod liver oil product (Seven Seas Neutrataste, Seven Seas Ltd.) 1 gram daily for 3 months might decrease pain, morning stiffness, and swelling in people with symptoms suggestive of RA who have not received any prior treatment (94757). Other clinical research shows that taking cod liver oil and fish oil (Seven Seas Marine Oil, Seven Seas Ltd.) 10 grams daily for 36 weeks can reduce NSAID use in patients with RA. About 4-fold more patients taking cod liver oil and fish oil can reduce NSAID intake by at least 30% when compared with placebo (65855). It is unclear if this effect is due to cod liver oil, fish oil, or the combination.
• Vitamin D deficiency. It is unclear if oral cod liver oil is beneficial as a vitamin D supplement. Details: Cod liver oil is sometimes used as a source of vitamin D. Evidence from population research shows that increased daily intake of cod liver oil supplements is associated with higher serum levels of vitamin D (94760). Also, a population study of postmenopausal women in northern Scotland shows that those taking a daily cod liver oil supplement are less likely to be vitamin D deficient during the winter and spring than those not taking a supplement (94761). However, preliminary clinical research shows that taking a low dose of cod liver oil (Möller Axellus AS) orally to provide 200 IU of vitamin D daily for 8 weeks during the winter does not maintain serum vitamin D at typical summer levels (94755).
• Wound healing. Although there has been interest in using topical cod liver oil for wound healing, there is insufficient reliable information about the clinical effects of cod liver oil for this condition. More evidence is needed to rate cod liver oil for these uses.

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LIKELY SAFE ...when used orally and appropriately. In clinical studies of cod liver oil in adults, a dose of 10 mL daily has been used safely for up to 24 weeks (3398), a dose of 15 mL daily has been used safely for 16 weeks (7360), and doses of 20 mL to 30 mL daily have been used with apparent safety for between 2 weeks and 8 weeks (3399,4026,10083,94758,94759,94754). Cod liver oil is a source of vitamins A and D. Dose amounts should not exceed the recommended dietary allowances (RDAs) of these vitamins. For vitamin A, the RDAs are 900 mcg (3000 units of retinol) daily for men and 700 mcg (2333 units of retinol) daily for women (7135). For vitamin D the RDAs are 15 mcg (600 units) daily for all adults up to 70 years of age, and 20 mcg (800 units) daily for older adults (91703).

POSSIBLY UNSAFE ...when used orally in excessive doses. Avoid doses of cod liver oil that contain more than the Tolerable Upper Intake levels (ULs) of vitamins A and D. For vitamin A the ULs are 3000 mcg (10,000 units of retinol) daily for adults and 2800 mcg (9333 units of retinol) daily for teenagers aged 14 years to 18 years (7135). For vitamin D, the UL is 100 mcg (4000 units) daily for everyone 9 years of age and older (91703). There is also concern that higher doses might increase bleeding risk. Cod liver oil in doses of 20-40 mL daily has been associated with prolonged bleeding time and reduced platelet aggregation in healthy volunteers (4025,4026,10083,91701,91702). There is insufficient reliable information available about the safety of cod liver oil when used topically.

CHILDREN: LIKELY SAFE
when used orally and appropriately in doses providing no more than the recommended dietary allowances (RDAs) of vitamins A and D. For vitamin A, the RDAs are 400 mcg (1333 units of retinol) daily up to age 6 months, 500 mcg (1667 units of retinol) daily for ages 6 months to 12 months, 300 mcg (1000 units of retinol) daily for ages 1 year to 3 years, 400 mcg (1333 units of retinol) daily for ages 4 years to 8 years, and 600 mcg (2000 units of retinol) daily for ages 9 years to 13 years (7135). For vitamin D, the RDAs are 10 mcg (400 units) daily for infants up to 12 months of age, and 15 mcg (600 units) daily for ages 1 year to 13 years (91703). In clinical studies, children aged 6 months to 1 year have safely received cod liver oil 2.5 mL daily for 5 months, and children aged 1 year to 5 years have safely received 5 mL daily for 5 months (94756).

CHILDREN: POSSIBLY UNSAFE
when used orally in excessive doses. Avoid doses of cod liver oil that contain more than the Tolerable Upper Intake levels (ULs) of vitamins A and D. For vitamin A, the ULs are 600 mcg (2000 units of retinol) daily for infants and children up to 3 years of age, 900 mcg (3000 units of retinol) daily for ages 4 years to 8 years, and 1700 mcg (5667 units of retinol) daily for ages 9 years to 13 years (7135). For vitamin D, the ULs are 25 mcg (1000 units) daily for infants up to 6 months, 38 mcg (1500 units) daily for ages 7 months to 12 months, 63 mcg (2500 units) daily for ages 1 year to 3 years, 75 mcg (3000 units) daily for ages 4 years to 8 years, and 100 mcg (4000 units) daily for ages 9 years and above (91703).

PREGNANCY: POSSIBLY SAFE
when used orally and appropriately in doses providing no more than the recommended dietary allowances (RDAs) of vitamins A and D. For vitamin A, the RDAs are 770 mcg (2567 units of retinol) daily for pregnant women over 18 years of age, and 750 mcg (2500 units of retinol) daily for pregnant teenagers 14 years to 18 years of age (7135). For vitamin D, the RDA is 15 mcg (600 units) daily for pregnant women of all ages (91703). In clinical research, cod liver oil (Peter Möller, Oslo, Norway) 10 mL orally daily (providing vitamin A 1170 mcg and vitamin D 10 mcg daily) has been used safely from week 17 of pregnancy until delivery, and continuing for 3 months during lactation (94763).

PREGNANCY: POSSIBLY UNSAFE
when used orally in excessive doses. Avoid doses of cod liver oil which contain more than the Tolerable Upper Intake levels (ULs) of vitamins A and D. For vitamin A, the ULs are 3000 mcg (10,000 units of retinol) daily for pregnant women over 18 years of age, and 2800 mcg (9333 units of retinol) daily for pregnant teenagers aged 14 years to 18 years (7135). For vitamin D, the UL is 100 mcg (4000 units) daily for pregnant women of all ages (91703).

LACTATION: POSSIBLY SAFE
when used orally and appropriately in doses providing no more than the recommended dietary allowances (RDAs) of vitamins A and D. For vitamin A, the RDAs are 1300 mcg (4333 units of retinol) daily for lactating women over 18 years of age, and 1200 mcg (4000 units of retinol) daily for pregnant teenagers aged 14 years to 18 years (7135). For vitamin D, the RDA is 15 mcg (600 units) daily for lactating women of all ages (91703). An Icelandic cod liver oil, 10 mL daily, has been used safely for 4 months during lactation (94764).

LACTATION: POSSIBLY UNSAFE
when used orally in excessive doses. Avoid doses of cod liver oil which contain more than the Tolerable Upper Intake levels (ULs) of vitamins A and D. For vitamin A, the ULs are 3000 mcg (10,000 units of retinol) daily for lactating women over 18 years of age, and 2800 mcg (9333 units of retinol) daily for lactating teenagers aged 14 years to 18 years (7135). For vitamin D, the UL is 100 mcg (4000 units) daily for lactating women of all ages (91703).

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, cod liver oil may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details High doses of cod liver oil, 20-40 mL daily, have been associated with prolonged bleeding time and reduced platelet aggregation in healthy volunteers (4025,4026,10083,91701,91702).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = A Theoretically, taking cod liver oil with antidiabetes drugs might increase the risk of hypoglycemia.  Details Some clinical research shows that cod liver oil may lower blood glucose levels in women with gestational diabetes who are already taking antidiabetes drugs when used for at least 12 weeks. However, it does not appear to have any effect on blood glucose when used for shorter durations (101988). Until more is known, use caution.

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Theoretically, taking cod liver oil with antihypertensive drugs might increase the risk of hypotension.  Details Cod liver oil can lower blood pressure and might have additive effects in patients treated with antihypertensives (1001,1020,3399); use with caution.

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General ...Orally, cod liver oil is generally well tolerated. Topically, adverse effects are rare. However, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Flatulence, gastrointestinal upset, heartburn, and nausea.
Serious Adverse Effects (Rare):
Orally: There are rare reports of lipoid pneumonia.

Gastrointestinal ...Orally, flatulence, heartburn, nausea, and gastrointestinal upset are the most frequently reported adverse effects of cod liver oil (3398,94757). Diarrhea also been reported rarely (101990).

Hematologic ...Orally, there is a case report of melena, bleeding duodenal ulcer, and anemia in a 60 year old man who was taking cod liver oil 5 mL daily in combination with other supplements, including fish oil, flaxseed oil, chlorella, and sea buckthorn, which increased his intake of omega-3 fatty acids to more than 21 grams daily (94751).

Immunologic ...Topically, cod liver oil may cause allergic contact dermatitis. There is a case report of allergic contact dermatitis in an 80-year-old woman being treated for leg ulcers with various topical products including 40% cod liver oil ointment (Dermovitamina, Pasquale SRL). She developed severe itchy papules and vesicles requiring treatment with topical corticosteroids and antihistamines, and had a positive skin test to cod liver oil but no other ingredients in the various topical products used (94762).

Neurologic/CNS ...Orally, headache and dizziness have been reported in a single patient each after a single dose of cod liver oil (101990).

Pulmonary/Respiratory ...Data from population surveys of adults in Norway conducted in the 1990s suggests that daily consumption of cod liver oil for at least a month is associated with a 1. 6-fold increase in the odds of adult-onset asthma about 11 years later, when adjusted for several confounding factors (94752). However, the cod liver oil that was commercially available in the 1990s in Norway contained high levels of vitamin A (1000 mcg per 5 mL; equivalent to 3333 units of retinol). It is thought that accumulation of vitamin A in the lungs contributed to the development of asthma.
A case report describes a 63-year-old white woman with a history of smoking and polyarthropathy who underwent a lobectomy after identification of a mass in her lung. This was identified as lipoid pneumonia, thought to be due to her regular intake of cod liver oil capsules (3396).

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