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Human liver studies reveal more about vitamin A excess than blood tests, which can be misleading. See just how toxic we are!
“Vitamin A deficiency” receives considerable attention worldwide, particularly in children and populations affected by malnutrition. Yet a very different body of research deserves attention: studies in which researchers actually measured vitamin A stored in human livers.
Beginning decades ago, autopsy studies from countries around the world revealed enormous differences in liver vitamin A concentrations between individuals. More importantly, some studies found surprisingly large percentages of people with liver concentrations that would now be considered excessive or hypervitaminotic.
These findings raise an important question: Could vitamin A excess be more common than blood tests suggest?
The Liver, Not the Blood, Holds Most Vitamin A
Unlike water-soluble nutrients that are readily excreted, vitamin A is fat-soluble and can accumulate in the body. The liver is its principal storage location.
Researchers have recognized this for many decades. A 1962 New Zealand autopsy study explained that because the liver contains the body’s main vitamin A reserves, hepatic concentrations provide a useful measure of vitamin A status.
This creates a practical problem. We can easily draw blood, but we cannot routinely remove liver tissue from healthy people simply to measure their vitamin A reserves.
Consequently, serum retinol is commonly used to assess vitamin A status. But serum retinol and liver vitamin A are not interchangeable measurements.
One particularly revealing 1974 study measured both plasma and liver vitamin A in 84 people in Bangkok who had died in accidents. Liver concentrations ranged dramatically, from 7.5 to 3,200 μg/g, while plasma retinol showed essentially no correlation with hepatic stores.
A modern review discussing this research confirms the significance of the discrepancy. Among three people in the Bangkok study with very low plasma retinol, one had (what were considered) deficient liver reserves, another had “adequate” reserves (what could be considered on their way to being toxic), and the third actually had hypervitaminotic liver stores.
That is an important finding. Low vitamin A in the blood does not equal low vitamin A in the liver.
What Constitutes High Liver Vitamin A?
Modern research often defines hypervitaminosis A as total liver vitamin A reserves of 1 μmol/g or greater, equivalent to roughly 286 μg/g.
For simplicity, approximately 300 μg/g liver can be used when looking back at older studies.
New Zealand: Particularly High Stores in Children
The 1962 New Zealand study examined liver samples collected at autopsy in 1951 and again in 1960–61.
Across 110 subjects, the average liver vitamin A concentration was 1,006 IU/g. Children between 1 and 10 years old had considerably higher stores, with a median of 1,982 IU/g.
The researchers discussed several possible sources of vitamin A exposure, including butter, dietary carotene and preformed vitamin A, as well as fish-liver-oil preparations.
The finding is notable because the very age group we often associate with concerns about inadequate vitamin A had some of the highest liver reserves in the study.
Ghana: Almost Half Had High Liver Concentrations
A 1963 study of Ghanaians produced an even more remarkable result.
Researchers examined 49 livers. Twenty-four contained more than 300 μg of vitamin A per gram of liver. That represents approximately 49% of the samples.
The average for the group was 409 μg/g, already above the approximately 300 μg/g comparison level. The highest measured concentration was an extraordinary 3,635 μg/g.
A subsequent investigation of Ghanaian tissues again found unusually high hepatic vitamin A. The mean was approximately 490 μg/g, with values reaching 1,900 μg/g.
Diet is particularly interesting in this population because carotene-rich foods, including palm oil, were important sources of vitamin A. The findings therefore challenge the idea that very high liver vitamin A is relevant only to people taking unusually large quantities of vitamin A pills.
Washington, D.C.: High Stores in Nearly One-Quarter of Samples
Another large autopsy study was conducted in metropolitan Washington, D.C. Researchers measured vitamin A and carotene in 329 liver samples in the 1973 study.
The published distribution shows that approximately 24% had liver vitamin A concentrations of 300 μg/g or greater.
At the higher end, 11% exceeded 500 μg/g, and approximately 3% reached at least 1,000 μg/g.
One specimen contained an astonishing 4,921 μg/g.
These measurements do not fully establish that one-quarter of the Washington population was suffering from clinically apparent vitamin A poisoning. But they raise that question, and they do show that very high vitamin A liver accumulation was not limited to isolated cases.
Today’s Population
How about today’s population?
Yes, it’s likely that vitamin A toxicity has increased worldwide, and that 24% of the population in the U.S. is the best case scenario. It’s more likely a much higher number.
Vitamin A was already being added to reduced-fat and skim milk by 1973, but by 1978, the Pasteurized Milk Ordinance required low-fat and skim milk to be fortified to at least 2,000 IU of vitamin A per quart. Americans subsequently shifted dramatically from whole milk toward low-fat and skim milk, meaning population exposure to added vitamin A from milk increased even if the amount added per quart remained 2,000 IU.
Many other foods were also fortified with vitamin A, and this trend increased with non-dairy milks.
Similar Findings Appeared in London and Singapore
The pattern continued in other parts of the world.
A 1982 London survey examined 364 autopsy specimens. Based on the study’s reported distribution, approximately 31% contained at least 300 mg/kg of liver vitamin A, equivalent to 300 μg/g. Eleven percent exceeded 500 mg/kg, and three subjects exceeded 1,000 mg/kg.
A 1988 study from Singapore examined 363 autopsy samples. Approximately 20% were at or above 300 mg/kg, while 9% exceeded 500 mg/kg and about 1% exceeded 1,000 mg/kg.
Taken together with the studies from Ghana, New Zealand, Thailand and the United States, these findings reveal something important: high hepatic vitamin A stores have been documented repeatedly across very different human populations.
Malnutrition Further Complicates the Picture
There is another reason to be cautious about interpreting low serum retinol as proof of inadequate vitamin A or lack of toxicity.
Vitamin A does not circulate freely in large quantities. Retinol is transported through the blood primarily by retinol-binding protein (RBP). Protein status, zinc status, infection and inflammation influence circulating retinol independently of the amount stored in the liver.
Protein-calorie malnutrition is particularly relevant in populations commonly described as vitamin A deficient. Inadequate protein can impair the production of transport proteins, while zinc deficiency can interfere with normal vitamin A mobilization.
Therefore, low serum retinol in a malnourished person may reflect a different nutritional problem (protein, zinc and taurine deficiency, to name a few).
The Bangkok findings illustrate just how important this distinction can be: People with low circulating retinol could have varying and even excessive liver stores.
What These Studies Should Change
These studies reveal our ability to determine an individual’s true vitamin A status is limited when we rely primarily on blood measurements.
The liver studies also demonstrate that human vitamin A stores span an enormous range. Some individuals contained only a few micrograms per gram of liver, while others contained concentrations in the thousands.
And unlike nutrients that must continually be replaced because they are rapidly eliminated, vitamin A accumulates.
This becomes especially relevant in a modern environment where vitamin A may come from multiple sources simultaneously: naturally vitamin A-rich foods, carotenoid-rich foods, fortified foods, supplements, infant formula, cod liver oil and other products.
The question should therefore not be, “Are we getting enough vitamin A?”
We should be asking: How much vitamin A are people already carrying in their bodies?
Human liver studies conducted across several decades suggest that, for a meaningful percentage of people, the answer may be considerably more than routine blood testing would lead us to believe.
Ongoing learning about toxicity
Much of what I’ve learned about vitamin A toxicity began with Grant Genereux’s ebooks (find his second book here) and continues through the research and teaching of Dr. Garrett Smith. For a deep dive into almost any topic related to toxicity, search Dr. Smith’s YouTube channel, Nutrition Detective.
Most of the research in this article was gathered by Dr. Smith. I’ve discussed his findings and provided links to the information he shared as well as adding my own.
My hope is that more people will continue to make the connection between vitamin A liver toxicity and general health challenges. When we reduce our intake of vitamin A from various sources, the liver begins to detox it aggressively. What followed for me and many others was astounding healing. To learn more about a low vitamin A diet and related topics, start here.
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