Cod Liver Oil

NutraPedia - Evidence-Based Supplement Research

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Research Overview

Research on cod liver oil (CLO) has been most developed in relation to its role as a dietary source of vitamin D (and, by extension, historical prevention and treatment of rickets) and, more broadly, as a “nutraceutical” containing fat-soluble nutrients and omega-3 fatty acids. The studies emphasize a long-standing evidence base linking vitamin D repletion—achieved historically via sunlight exposure or cod liver oil—to skeletal health through regulation of calcium/phosphate metabolism and bone mineralization. In contrast, more recent interest has expanded toward non-skeletal outcomes (e.g., immune/respiratory health and other chronic disease risks), but this area is characterized by mixed findings and methodological challenges, including the difficulty of applying drug-style randomized controlled trial (RCT) designs to a nutrient where baseline status, dose-response, and achieved blood levels may strongly influence outcomes.

The strongest evidence in the studies reviewed here supports cod liver oil’s historical effectiveness as an antirachitic intervention via vitamin D provision, consistent with established vitamin D biology and the well-documented prevention/cure of rickets. For acute respiratory outcomes, however, the highest-quality evidence cited is a large, quadruple-blinded RCT in Norway (n=34,601) using 5 mL/day CLO (10 µg vitamin D) over winter, which found no reduction in SARS-CoV-2 infection, serious COVID-19, or other acute respiratory infections compared with placebo; adverse effects were low grade. Additional mechanistic/preclinical work suggests potential antioxidant or protective effects in specific experimental contexts (e.g., mitigation of tartrazine-associated neurotoxicity in rat pups), and in vitro/chemical studies examine oxidation processes in lipids including cod liver oil, but these do not establish clinical efficacy in humans.

Key gaps include clarifying whether CLO confers benefits beyond correcting vitamin D deficiency and, if so, in which populations, doses, and outcome domains. More research is needed to disentangle effects attributable to vitamin D versus other CLO constituents (e.g., omega-3 fatty acids, vitamin A), to test clinically meaningful endpoints with designs that account for baseline nutrient status and achieved biomarker levels, and to evaluate longer-term outcomes and safety across subgroups. The nutraceutical review underscores that many claimed benefits for products including cod liver oil remain insufficiently clinically validated, indicating a need for well-designed human trials and rigorous evidence synthesis focused on specific indications rather than broad, non-specific health claims.

1. What conditions has Cod Liver Oil been studied for?

  • COVID-19 / SARS-CoV-2 infection and serious COVID-19 outcomes (hospitalization, dyspnoea, death) and other acute respiratory infections in adults (randomized placebo-controlled trial in Norway).

  • Rickets / vitamin D deficiency-related bone disease (historical and mechanistic context: cod liver oil and sunlight prevent/cure rickets; vitamin D2/D3 identified as antirachitic agents in cod liver oil).

  • Multiple sclerosis (MS) risk (Norwegian case-control study assessing cod liver oil/vitamin D3 supplementation at different ages).

  • Toxicant-related organ injury in animal models:

    • Tartrazine-associated neurotoxicity in rat pups (neurotransmitters, oxidative stress markers, apoptosis in brain cortex).

    • Sodium nitrite-induced liver damage in rats (liver enzymes, oxidative stress, inflammation marker MCP-1, mitochondrial function, DNA fragmentation).

  • Oxidative stability/oxidation of lipids (cod liver oil used as a lipid substrate in an in-vitro antioxidant study of saponarin; not a clinical condition but relevant to oxidation processes).

  • Contaminant exposure risk: mercury (Hg) content measured in cod liver oil supplements (food safety/toxicology assessment).

2. Does it work in treating those conditions? Summarize the evidence.

  • COVID-19 / acute respiratory infections (human RCT): No demonstrated benefit.

    • In a quadruple-blinded RCT of 34,601 adults given 5 mL/day cod liver oil (10 µg vitamin D) vs placebo for up to 6 months, cod liver oil did not reduce:

    • Positive SARS-CoV-2 test: 1.31% vs 1.32% (RR 1.00; adjusted CI 0.82–1.22).

    • Serious COVID-19: 0.70% vs 0.58% (RR 1.20; adjusted CI 0.87–1.65).

    • Self-reported acute respiratory infections: 22.94% vs 22.13% (RR 1.04; adjusted CI 0.97–1.11).

  • Rickets (historical evidence/mechanism): Strong historical support, but not tested in the provided modern trials.

    • Studies describe that cod liver oil and sunlight were observed to prevent and cure rickets, and that vitamins D2/D3 were identified as the antirachitic agents in cod liver oil.

    • These are not contemporary randomized trials in the provided text, but they support biological plausibility for rickets prevention/treatment via vitamin D repletion.

  • Multiple sclerosis risk (human observational): Associated with lower risk when used in adolescence; not proof of treatment.

    • In a case-control study (EnvIMS Norway; 953 MS cases, 1717 controls), self-reported cod liver oil use at ages 13–18 was associated with reduced MS risk (OR 0.67; 95% CI 0.52–0.86), while use in childhood was not (OR 1.01; 95% CI 0.81–1.26).

    • A dose-response was reported, with strongest association at estimated vitamin D3 intake 600–800 IU/day (OR 0.46; 95% CI 0.31–0.70; p-trend = 0.001).

    • Because this is observational and self-reported, it supports an association (risk reduction) but cannot establish causality or confirm cod liver oil as a treatment for established MS.

  • Toxicant-related injury (animal studies): Protective effects shown in rats; uncertain relevance to humans.

    • Tartrazine neurotoxicity (rat pups): cod liver oil co-administration largely “retrieved” neurotransmitter levels (GABA, dopamine, serotonin), improved antioxidant markers (SOD, catalase, glutathione), reduced malondialdehyde, and reduced apoptotic cells vs tartrazine alone.

    • Sodium nitrite liver injury (rats): cod liver oil reduced liver enzymes and improved histology; lowered oxidative stress markers (e.g., malondialdehyde, hydrogen peroxide, superoxide anion), reduced MCP-1, reduced DNA fragmentation, and restored cytochrome c oxidase activity after nitrite-induced reduction.

    • These are controlled animal experiments suggesting antioxidant/anti-inflammatory effects, but do not prove clinical benefit in humans for toxin exposures.

3. What health benefits does it have?

  • Vitamin D repletion-related benefits (most established domain: bone/mineral metabolism).

    • One abstract reiterates vitamin D’s essential role in calcium and phosphate metabolism and maintaining a healthy mineralized skeleton.

    • Historical studies link cod liver oil (a vitamin D source) to prevention/cure of rickets.

  • Possible reduction in MS risk when used during adolescence (observational evidence).

    • Adolescent cod liver oil use (13–18) was associated with lower MS risk (OR 0.67), with a reported dose-response and strongest association at 600–800 IU/day vitamin D3 (OR 0.46).

  • Potential antioxidant/anti-inflammatory and tissue-protective effects (preclinical evidence).

    • In rats, cod liver oil mitigated oxidative stress and cellular injury markers in models of neurotoxicity (tartrazine) and liver injury (sodium nitrite), including reductions in malondialdehyde and DNA fragmentation and improvements in antioxidant enzymes and mitochondrial function.

  • No demonstrated benefit for preventing COVID-19 or other acute respiratory infections at the studied dose in adults.

    • The large RCT using 10 µg/day vitamin D from cod liver oil showed no reduction in SARS-CoV-2 infection, serious COVID-19, or other acute respiratory infections.

4. Does it have any downsides or side effects?

  • Side effects in the large RCT were minimal.

    • In the 34,601-person RCT, only low-grade side effects were reported in both cod liver oil and placebo groups (no signal of major harm reported in the study).

  • Potential contaminant risk (mercury) depends on product quality.

    • A study measured mercury (Hg) content in dietary supplements including cod liver oils, highlighting that oils can be contaminated due to environmental pollution and that this could pose a potential health threat depending on levels and duration of use (the study is truncated and does not show the actual Hg results).

  • Evidence limitations and practical cautions (not fully addressed in the studies).

    • The studies reviewed here do not quantify risks such as excess vitamin A, bleeding risk, or interactions; therefore, conclusions about these potential downsides cannot be drawn from the supplied text alone.

5. Is it beneficial or harmful for any genetic variations (pharmacogenomics)?

  • No direct pharmacogenomic evidence for cod liver oil is provided in these studies.

    • One historical/scientific overview notes that genetic defects in vitamin D metabolism enzymes (25-hydroxylase, 24-hydroxylase, 1α-hydroxylase) and mutations in the vitamin D receptor can cause forms of rickets (e.g., vitamin D-resistant rickets). This implies that response to vitamin D (and thus cod liver oil as a vitamin D source) could vary by genotype, but the studies do not test cod liver oil outcomes by genotype.

  • MS study did not report genotype-specific effects.

    • The EnvIMS case-control analysis reports age-window and dose associations but does not stratify by genetic variants, so no cod liver oil pharmacogenomic conclusions can be made from it.

References

  1. Vitamin D for skeletal and non-skeletal health: What we should know.
    Nipith Charoenngam, Arash Shirvani, Michael F Holick (2019) - Journal of clinical orthopaedics and trauma
  2. Prevention of covid-19 and other acute respiratory infections with cod liver oil supplementation, a low dose vitamin D supplement: quadruple blinded, randomised placebo controlled trial.
    Sonja H Brunvoll, Anders B Nygaard, Merete Ellingjord-Dale, Petter Holland, Mette Stausland Istre, Karl Trygve Kalleberg, Camilla L Søraas, Kirsten B Holven, Stine M Ulven, Anette Hjartåker, Trond Haider, Fridtjof Lund-Johansen, John Arne Dahl, Haakon E Meyer, Arne Søraas (2022) - BMJ (Clinical research ed.)
  3. Vitamin D and bone health: What vitamin D can and cannot do.
    Michael F Holick (2024) - Advances in food and nutrition research
  4. Why do so many trials of vitamin D supplementation fail?
    Barbara J Boucher (2020) - Endocrine connections
  5. Comparative protective effects of royal jelly and cod liver oil against neurotoxic impact of tartrazine on male rat pups brain.
    Amany Abdel-Rahman Mohamed, Azza A A Galal, Yaser H A Elewa (2015) - Acta histochemica
  6. Flavonoids with potent antioxidant activity found in young green barley leaves.
    Masumi Kamiyama, Takayuki Shibamoto (2012) - Journal of agricultural and food chemistry
  7. What Is New in the Preventive and Therapeutic Role of Dairy Products as Nutraceuticals and Functional Foods?
    Ahmad Taha Khalaf, Yuanyuan Wei, Sadiq Jaafir Aziz Alneamah, Sarmad Ghazi Al-Shawi, Samiah Yasmin Abdul Kadir, Jamaludin Zainol, Xiaoming Liu (2021) - BioMed research international
  8. Rickets, Vitamin D, and Ca/P Metabolism.
    Walter L Miller, Erik A Imel (2022) - Hormone research in paediatrics
  9. Timing of use of cod liver oil, a vitamin D source, and multiple sclerosis risk: The EnvIMS study.
    Marianna Cortese, Trond Riise, Kjetil Bjørnevik, Trygve Holmøy, Margitta T Kampman, Sandra Magalhaes, Maura Pugliatti, Christina Wolfson, Kjell-Morten Myhr (2015) - Multiple sclerosis (Houndmills, Basingstoke, England)
  10. Hepatoprotective effects of cod liver oil against sodium nitrite toxicity in rats.
    Mohamed F Salama, Ahmed Abbas, Mohamed M Darweish, Amany A El-Hawwary, Mohammed M H Al-Gayyar (2013) - Pharmaceutical biology
  11. Mercury Exposure from the Consumption of Dietary Supplements Containing Vegetable, Cod Liver, and Shark Liver Oils.
    Barbara Brodziak-Dopierała, Agnieszka Fischer, Martyna Chrzanowska, Bożena Ahnert (2023) - International journal of environmental research and public health
  12. The comparison of the effect of soybean and fish oil on supplementation on menopausal symptoms in postmenopausal women: A randomized, double-blind, placebo-controlled trial.
    Bahareh Purzand, Samaneh Rokhgireh, Mansoore Shabani Zanjani, Nooshin Eshraghi, Mahdiss Mohamadianamiri, Arezoo Esmailzadeh, Ibrahim Alkatout, Georgios Gitas, Leila Allahqoli (2020) - Complementary therapies in clinical practice
  13. The causal effects of lifestyle, circulating, pigment, and metabolic factors on early age-related macular degeneration: a comprehensive Mendelian randomization study.
    Gang Shen, Yaqiong Chen, Jiahao Chen, Lingling Wang, Huanhuan Cheng, Bo Hu, Jiao Gong (2024) - Journal of translational medicine
  14. Polyunsaturated lipids and vitamin A oxidation during cod liver oil in vitro gastrointestinal digestion. Antioxidant effect of added BHT.
    Bárbara Nieva-Echevarría, Encarnación Goicoechea, María D Guillén (2017) - Food chemistry
  15. The historical evolution of thought regarding multiple micronutrient nutrition.
    Richard D Semba (2012) - The Journal of nutrition
  16. Maternal food-avoidance diets and dietary supplements during breastfeeding.
    Live S Nordhagen, Vibeke S Løfsgaard, Milada C Småstuen, Kari Glavin, Kai-Håkon Carlsen, Monica Hauger Carlsen, Berit Granum, Malén Gubrandsgard, Guttorm Haugen, Gunilla Hedlin, Christine M Jonassen, Björn Nordlund, Eva Maria Rehbinder, Knut Rudi, Carina M Saunders, Håvard O Skjerven, Anne Cathrine Staff, Cilla Söderhäll, Riyas Vettukattil, Hilde Aaneland, Karin C Lødrup Carlsen (2023) - Nursing open
  17. Risk factors for vitamin D deficiency in Abu Dhabi Emirati population.
    Amal Abdul Rahim Al Zarooni, Nico Nagelkerke, Fatima Ibrahim Al Marzouqi, Salma Hamad Al Darmaki (2022) - PloS one
  18. Vitamin D, cod liver oil, sunshine, and phototherapy: Safe, effective and forgotten tools for treating and curing tuberculosis infections - A comprehensive review.
    Patrick J McCullough, Douglas S Lehrer (2018) - The Journal of steroid biochemistry and molecular biology
  19. Cod liver oil intake and incidence of asthma in Norwegian adults--the HUNT study.
    Xiao-Mei Mai, Arnulf Langhammer, Yue Chen, Carlos A Camargo (2013) - Thorax
  20. Chemometric tools for the authentication of cod liver oil based on nuclear magnetic resonance and infrared spectroscopy data.
    Editha Giese, Sascha Rohn, Jan Fritsche (2019) - Analytical and bioanalytical chemistry


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This article summarizes published research for educational purposes. It is not medical advice. Talk to your doctor before starting, stopping, or changing any supplement or medication.

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