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The Reality of Vitamin A Toxicity When Taking Omega 3 Supplements

Summary

Vitamin A toxicity can occur with large quantities of vitamin A supplements, large quantities of cod liver oil with or without these supplements, and large quantities of fruits and vegetables combined with vitamin A supplements or cod liver oil. Following quantities should be kept in mind for the omega-3 related vitamin A toxicity:
1. If the preformed omega-3 supplement does not contain vitamin A then there is no risk of vitamin A toxicity from taking this supplement.
2. If cod liver oil is consumed, for omega-3 and other beneficial supplements, then an acute consumption of 100x (25 tablespoons) in adults in 25x (2.5 tablespoons) in children can lead to acute toxicity.
3. For chronic toxicity data is clearer for children with 450 mcg RAE/kg of body weight daily consumed for many months or years may lead to vitamin A toxicity. The elderly seem to be more vulnerable, but an exact amount of cod liver oil quantity is not adequately studied.
4. Combining multiple sources of vitamin A can result in toxicity.

If you research omega-3 you will come across several articles describing vitamin A toxicity (hypervitaminosis A) as a potential side effect. I wanted to understand the reason, the risk, and the incidence of vitamin A toxicity in omega-3 supplement users. The following are my findings (case reports) with evidence.

Today we will discuss hypervitaminosis A (vitamin A toxicity) from taking omega 3 supplements.

Mobeen Syed MD, MSc (Comp Sci,) MSc (Comp Sci), BSc (English), Dip Entrepreneurship, Member Board of Advisors Annals of KEMU, Visiting Faculty KEMU.

Signs and symptoms of vitamin A toxicity

According to the NIH the symptoms of vitamin A toxicity include blurred vision, headaches, dry skin, hair loss, fatigue, and bone pain. Typical physical examination findings may include dryness of the conjunctiva and mucous membranes, scaly skin, alopecia, papilledema, bone tenderness, and hepatomegaly [9].

Discussion

Omega-3 can be obtained from a variety of sources. Read my article for the sources of it. Out of all sources, only cod liver oil contains large amounts of vitamin A. Other sources do not contain vitamin A. Importantly manufacturers of omega-3 supplements provide the information on the label if their product contains vitamin A. If vitamin A is present in their product, then the amount and the percentage of daily intake of vitamin A contained in each serving is mentioned as well. The question then becomes, how much cod liver oil consumed and for how long can lead to vitamin A toxicity? Turns out the answer isn’t clear. Let’s review some of the available evidence.

According to the office of dietary supplements (ODS) of the national institute of health (NIH) the daily RDA for vitamin A is 900 micrograms RAE for adult male and 700 micrograms RAE for adult females. A four-year-old child is suggested to take a 400 mcg RAE of vitamin A daily [2].

Note that one tablespoon of cod liver oil contains 13,600 IU of vitamin A [4]. This comes to 4,080 mcg RAE [5]. This amount is more than 4x or 400% of the daily RDA in adults and 10x the daily RDA for a four-year-old child.

NIH ODS writes that the daily safe upper limit for the preformed vitamin A is 3,000 micrograms RAE in adults 19 years and above [2]. NIH ODS writes:

“Getting too much preformed vitamin A (usually from supplements or certain medicines) can cause severe headache, blurred vision, nausea, dizziness, muscle aches, and problems with coordination. In severe cases, getting too much preformed vitamin A can even lead to coma and death.”

Read the nuances of hypervitaminosis A in the link provided [2]

In the above paragraph notice that a quantity and the duration of use (number of days, weeks, or months) is not provided. Instead, NIH-ODS writes a vague statement, “getting too much preformed vitamin A …” Not much help from this paragraph. This means we need to continue to search further in the evidence for the amounts and the duration of vitamin A use that can lead to vitamin A toxicity. We have already noted that one tablespoon of cod liver oil has more than four times the daily RDA for adult males and females. Let’s review if there are any studies or case reports of vitamin A toxicity after cod liver oil usage.

Vitamin A toxicity in a four-year-old child

In this case report published in 2020 a four-year-old child presents with the signs and symptoms that eventually were diagnosed as vitamin A toxicity [6]. The authors wrote:

“After the patient had spent 2 weeks in hospital, we received the results of his outstanding investigations (Box 1). His parathyroid hormone-related peptide and total 25(OH)D levels were normal, but the vitamin A level was significantly elevated at 4.1 (reference 1.0–1.6) μmol/L. Because of his elevated vitamin A level, we carefully reviewed his diet and supplement intake. He was on a predominantly plant-based diet, and we estimated his vitamin A intake to be between 1528 μg and 3304 μg of retinol activity equivalents (RAE) per day, or 31 087–63 507 international units (IU) per day (recommended intake for children at the age of our patient is 400 μg/d RAE). We referred to the US Department of Agriculture to provide the levels of vitamin A in the foods (https://fdc.nal.usda.gov/) and the conversion of factors for RAE and IU from the US National Institutes of Health (Box 2). The patient’s main sources of vitamin A included 1–2 cups of kale, 2–3 cups of green vegetables, 2–3 cups of fruit and 4 oz of meat per day (nonliver), plus a multivitamin containing vitamin A as β-carotene (28 μg RAE). He had previously been taking cod liver oil supplements (276 μg/day RAE) for more than 1 year, but had stopped many months previously.”

This patient had 3-4x the blood level of vitamin A and had been consuming about 4-8x the daily RDA of vitamin A for his age range for over a year.

Three cases of vitamin A overdose in children after taking chewable candies

Another case series published in 2006 mentions overdose in children who had taken 200,000 to 300,000 IU (60,000 mcg RAE to 90,000 mcg RAE) daily in the form of chewable candies that contained vitamin A. Note that consuming such large amount of vitamin A can lead to acute vitamin A toxicity over the course of hours to days. Also note that 60,000 mcg RAE translates to about 15 tablespoons of cod liver oil [7].

Vitamin A Toxicity with Acute and Chronic Consumption

Acute toxicity of vitamin A occurs within hours to days when an adult takes 100x more vitamin A than recommended. This means about 25 tablespoons of cod liver oil (considering 1 tablespoon of cod liver oil contains 4x the daily vitamin A allowance). On the other hand, acute toxicity in children can occur within hours to days at a 25x RDA. As an example, for a four-year-old child a tablespoon of cod liver oil contains 10x the daily RDA of vitamin A. This means a four-year-old child can potentially develop vitamin A toxicity with 2.5 tablespoons of cod live oil consumption[8].

Chronic toxicity in children is observed at many months to years of vitamin A consumption at 1500 IU/kg body weight (450 mcg RAE/kg/day).

The elderly may be more vulnerable to vitamin A toxicity; however, the mechanism is not fully understood. There also are no adequate studies to understand the quantities that may cause toxicity. Authors in this article write:

“Individual tolerances to different amounts of vitamin A ingested on a chronic basis have not been adequately studied. The role that genetics may play in this regard is unknown (2, 20, 42). If hypervitaminosis A is indeed a growing problem, more efforts are needed to characterize the circulation and storage of vitamin A at different stages of the life cycle.”

Our conclusion is that vitamin A toxicity can occur with large quantities of vitamin A supplements, large quantities of cod liver oil with or without these supplements, and large quantities of fruits and vegetables combined with vitamin A supplements or cod liver oil. Following quantities should be kept in mind for the omega-3 related vitamin A toxicity:

If the preformed omega-3 supplement does not contain vitamin A then there is no risk of vitamin A toxicity from taking this supplement.
If cod liver oil is consumed, for omega-3 and other beneficial supplements, then an acute consumption of 100x (25 tablespoons) in adults in 25x (2.5 tablespoons) in children can lead to acute toxicity.
For chronic toxicity data is clearer for children with 450 mcg RAE/kg of body weight daily consumed for many months or years may lead to vitamin A toxicity. The elderly seem to be more vulnerable, but an exact amount of cod liver oil quantity is not adequately studied.
Combining multiple sources of vitamin A can result in toxicity.

References

Omega-3 Fatty Acids https://ods.od.nih.gov/factsheets/Omega3FattyAcids-HealthProfessional/
Vitamin A and Carotenoids https://ods.od.nih.gov/factsheets/VitaminA-Consumer/
Regular consumption of cod liver oil is associated with reduced basal and exercise-induced C-reactive protein levels; a prospective observational trial – PMC
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240263/
Fish oil, cod liver, 1 tbsp – Health Encyclopedia – University of Rochester Medical Center
https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=76&contentid=04589-2
Vitamin A IU to mcg Conversion Calculators
https://belabelwise.org/conversion-calculator/
Refractory hypercalcemia owing to vitamin A toxicity in a 4-year-old boy – PMC https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828856/
Risk of Vitamin A Toxicity From Candy-Like Chewable Vitamin Supplements for Children | Pediatrics | American Academy of Pediatrics https://publications.aap.org/pediatrics/article-abstract/118/2/820/69014/Risk-of-Vitamin-A-Toxicity-From-Candy-Like?redirectedFrom=fulltext?autologincheck=redirected
The acute and chronic toxic effects of vitamin A – ScienceDirect
https://www.sciencedirect.com/science/article/pii/S0002916523292710?via%3Dihub
Vitamin A Toxicity – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK532916/