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clear search termsUnsung Immune System Hero: Vitamin A
Vitamin Who? Alas, this essential nutrient often takes a back seat to its celebrity counterpart Vitamin D. Unfortunately Vitamin A deficiency is internationally profound, widespread, and often at play in early childhood death from infectious disease in third-world countries. While overt, life-threatening Vitamin A deficiency is rare in first world countries, most of us are unaware of the impact (and common risk) of having suboptimal or insufficient Vitamin A.
Vitamin A is a fat-soluble nutrient, an antioxidant, and a hormone. It is especially critical for the ongoing health of epithelial cells that line tissues (e.g. skin, respiratory tract, GI tract, urinary tract). It is also crucial for good vision (hence the old adage of eating carrots for healthy eyes), and insufficiency can lead to impaired vision or night blindness (keep this in mind with your older patients in particular). Vitamin A supplementation has also been shown to improve eczema, lower the incidence of kidney stones, protect against the formation of stress-related ulcers, alleviate dry skin or brittle nails, and reduce the incidence of ear infections in children.
Vitamin A also plays a major role in immune function. Vitamin A modulates the action of effector T cells and thus helps to regulate inflammation and also increases T-regulatory cells, which helps to balance immune response (pro- vs. anti-inflammatory) and prevent autoimmune activation (e.g. where Th-17 dynamics are prominent). Vitamin A is also required for secretory IgA production, the dominant mucosal antibody protection (e.g. where food and microbes meets intestinal villi in the intestines). Insufficient levels can lead to loss of immune tolerance and increased susceptibility to infections, allergies, and auto-immune illness.
Vitamin D and Vitamin A have synergistic effects on immune function, and their receptors are actually activated together (via a complex of the vitamin D receptor and the retinoic acid receptor). This means that each needs the other in order to have activated effects, and both need to be sufficient to support their mutual, optimal benefits in the body (perhaps especially as it relates to IgA function?). Given the widespread use of high-dose Vitamin D today, this raises an interesting question as to whether this practice may contribute to greater insufficiency of Vitamin A, especially in those already vulnerable to that gap.
Why are we already wrestling with suboptimal Vitamin A status? As we all well know, the typical modern diet is calorie- and chemical-rich but often lacking in nutrition due to excessive processing/refinement. Even when foods are nutrient-dense, only an estimated ~40-60% of beta carotene (the most prevalent pro-vitamin A precursor) from plant sources is absorbed. Foods such as sweet potatoes, winter squashes (e.g. butternut), carrots, and parsley are rich in beta carotene. Its conversion to Vitamin A is carried out by enzyme conversion in the gut (enterocytes) and regulated by overall Vitamin A levels. Animal foods such as whole eggs (especially from free-range chickens), beef, grass-fed butter, organ meats (e.g. liver), and oily fish (e.g. mackerel) contain notable amounts of fully formed vitamin A.
Several key populations may have poor carotene conversion to true Vitamin A. Research shows there can be notable genetic variability in our conversion capability. This critical conversion happens in the lining of your intestines and is also dependent on several nutrient co-factors; those with iron (e.g. anemia) or zinc insufficiency may struggle. Vitamin A conversion may also be impaired in individuals who have gastrointestinal issues that promote mucosal damage/dysfunction e.g. food allergies/sensitivities, parasite infection, bacterial dysbiosis, digestive enzyme deficiency, poor gallbladder emptying or bile function, inflammatory bowel disease, or celiac disease.
Conversion of beta carotene to the active form of Vitamin A is also regulated directly by thyroid hormone. As we know, subclinical hypothyroidism is quite common in our practices. Even among those being treated with standard T4-only meds, many may still have intracellular hypothyroid function due to inadequate conversion to (and/or action of) T3 thyroid hormone intracellularly (and Vitamin A is required for thyroid hormone receptor function).
Vitamin A levels may also be notably lower in those with type 2 diabetes (and is not improved by glucose- or lipid-lowering medication). Perhaps not surprisingly, vitamin A insufficiency can promote loss of pancreatic β-cell mass and hyperglycemia. Is this cause or effect or both, though, as Vitamin A may be playing a key role in supporting increased antioxidant demand from hyperglycemia?
Given all these factors at play in Vitamin A insufficiency, supplementation may be valuable for some individuals to help ensure optimal levels. Recommended intake is typically about 3000 IU/day for adults (with max regular daily intake ~10,000 IU/day). Beyond dietary sources, supplementation with a combination of beta carotene and fully-formed vitamin A (i.e. retinol palmitate) may be beneficial and should be taken with a meal that includes at least 10g fat (to ensure bile stimulation to support digestion/absorption). Beta carotene supplementation is contraindicated for smokers.
Vitamin A toxicity is possible though uncommon and has typically been found to occur in adults with high fully formed Vitamin A supplement (ongoing 50,000+ IU/day). Pregnant women are especially cautioned not take more than 10,000 IU/day from all sources. Of note, “toxicity” incidents may actually be caused/exacerbated by an imbalance of Vitamin A and D given the factors mentioned above? Common early signs of Vitamin A toxicity include itchy skin, headaches, bone pain, and nausea which resolve quickly after reducing intake.
Vitamin A is another example of a nutrient that, in our healthcare culture, is not often clinically “deficient” (and hence would be dismissed by many practitioners) but can indeed be commonly “insufficient” (meaning there is room for improvement e.g. establishing serum levels in the upper half of the normal reference range). The difference between these two terms can make the critical distinction for your client between surviving and thriving.
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31 Questions for “Unsung Immune System Hero: Vitamin A”
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15.1
The nutritional needs of each person vary based on their, age, nutritional choices, genetics, etc. There are many people who could benefit from better nutritional supplements, or better food choices or both. If you are interested in learning more about the B vitamins we recommend this post: https://schoolafm.com/ws_clinical_know/homocysteine-an-often-hidden-heart-disease-risk-factor/
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Jenny Andrade says:
What vitamin A level would you consider optimal? I had a clients vitamin A level checked and it came back at 31.6ug/dl (RR 20.1-62). Considering how low it is to the bottom of the reference range, I am assuming she is slighly deficient (also lots of illnesses), but do I want this to be in the upper half or upper 3/4 of the reference range? Thank you!
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14.1
This is a great question as the “optimal” level for this person may be unique. I agree that the levels you have measured seem to be suboptimal or even insufficient given many illnesses. You will find out through your work together if it needs to be in the upper half or even in the upper quarter of the reference range. In addition, always consider the whole picture. without hyper-focus on one single nutrient, as there are many other factors that influence immune function, such as overall psychological and physiological stress load, other nutrients, etc.
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Melanie Rodewald says:
Are you able to recommend Vitamin A dosing for children? Say, 2-8 years old? Obviously, it is always best to test don’t guess but is it reasonable to treat a child with eczema for a defined period of time?
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13.1
Vitamin A supplement and many other supplement dosages in children can vary greatly depending on their age and most importantly on their body weight. The best resource that we can recommend for working with children is this book:
https://www.amazon.com/Healing-New-Childhood-Epidemics-Groundbreaking/dp/0345494512
As for official guidelines on vitamin A supplementation here are a couple of resources:
https://www.ncbi.nlm.nih.gov/books/NBK185173/
https://pubmed.ncbi.nlm.nih.gov/28282701/
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Jordan Blackburn says:
Is there something equivalent to organic acid tests to determine the levels of intracellular retinol / retinoic acid? Can practitioners use something more reliable than a diet diary, symptoms (i.e., cravings for carrots) and related blood markers (i.e., ceruloplasmin) to determine that the body actually requires more Vitamin A?
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12.1
The test that comes to mind here is a Spectracell Micronutrient panel that measures nutrients both in plasma and also intracellular levels in white blood cells:
https://www.spectracell.com/micronutrient-test-panel
Vibrant micronutrient panel is another option:
https://www.vibrant-america.com/micronutrient/
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11
I am curious, although rare, what would cause a significantly higher than reference range level of Vit A ( I have recently come across this with testing)? Aside from screening for excessive food intake (like eggs), and making sure no intake of supplements with Vit A, potential for lab error ( would like to recheck in the future to see level again) what other reasons are there? Since Vit D and Vit A are binding to the same receptor is it possible that a suboptimal or deficiency in Vit D could make the cells bind more to Vit A and uptake it more regularly? Thank you!
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11.1
2/3 to 3/4 of the body’s Vitamin A is stored in the liver, so any dis-ease dynamic that involves higher liver tissue damage/turnover OR any healing dynamic that reduces hepatic fat (fatty liver) will likely increase measurable Vitamin A in the blood. If you want a geek dive on this topic, this may interest you: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3042718/ . Other than what you mention, another potential cause of elevated vitamin A is long-term use of certain acne treatments that contain high doses of vitamin A, such as isotretinoin. In addition, many foods are fortified with vitamin A, so a thorough dietary review of commonly eaten processed foods may reveal some hidden sources. Organ meats such as liver are exceeding high in Vitamin A, and regular intake could easily boost levels well up into or over the normal reference range.
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10
Hi Tracy,
I’ve read that beta-carotene is not recommended for the smokers and ex-smokers. Is it safe to recommend a fully formed vitamin A (retinoid) as a supplement instead (for a smoker whose cellular vitamin A levels are clinically low, as well as free T3 is low indicating poor conversion and lack of required nutrients)?
Thank you!-
10.1
SAFM Team says:
Your question is a great reminder of some key devil-in-the-detail: nutrients are synergistic and do not act alone in the body. This is a resource I recommend you review: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082716/ . In fact, in the well-known study you reference, the effect of β-carotene supplementation on smokers’ risk of cancer was further modified by dietary vitamins C and E intake and overall fruit and vegetable intake. This highlights the truth that supplements are never a substitute for real, nutrient-rich foods. Smoking modifies beta carotene (BC) metabolism which leads to decreases in plasma BC levels but increased degradation of BC into numerous cleavage products such as epoxides and aldehydes which can have various harmful effects e.g. interference with retinoid signalling. In terms of nutrient synergy, for example, Ample Vitamin C may help to reduce BC oxidation. If you have evidence of insufficient Vitamin A, then I believe addressing it directly is merited (not with BC). Just remember to check Vitamin D sufficiency (D and A are taken up together) and also zinc sufficiency (a key cofactor for synthesis of retinoid binding protein) and increase low’n’slow. As you know, zinc is also critical (along with selenium) for conversion of T4 to T3 thyroid hormone as well.
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Claudia says:
It seems like the true problem is not so much the deficiency per se, but the inability of the body to absorb it, due to insufficiency of other co-factors, like it often happens in biology.
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9.1
Yes, indeed, there can be plenty of Vit A around but if the body is limited by genetic factors, or gut issues or by lack of co-factors necessary for absorption, Vit A won’t be efficiently converted to it’s active form and absorbed.
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Tammy Valta says:
Is there any liquid form of Vit A you would recommend for teen who are not swallowing supplements?
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8.1
There are many great products on the market, here is a couple of examples of products that are widely available:
https://www.amazon.com/Vitamin-Drops-Pure-Seeking-Health/dp/B00AA1G9C2
https://www.amazon.com/Klaire-Labs-Micellized-Vitamin-Liquid/dp/B004JP675O/
https://www.swansonvitamins.com/world-organic-vitamin-a-emulsion-liquid-2-fl-oz-liquid
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Lisa Jackson says:
How much vitamin A would you recommend for acute acne and for how long?
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7.1
I would seek Vitamin A labwork and respond accordingly; excessive Vitamin A might exacerbate existing acne, so I do think caution is merited. In the absence of data, I would likely focus on increasing intake via foods (e.g. liver, egg yolks), but if not, one might do a trial in this case of 5000 IU/day for a month (ensuring sufficient D and K2 first!) and gauge effect. Keep in mind too that zinc is needed to support Vitamin A absorption, so this may be a point of interconnectedness in many individuals (given the role of zinc also in optimizing immune function and androgen balance).
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David Sander says:
Thank you for this balanced and technical report on Vitamin A. As an older runner of 63, I started reading the recent research finding on vitamin D3 years ago and worked up to taking 10,000 IU daily. This resulted in my not tripping and falling during runs along with other improvements.
I later noticed that my skin scrapes were not healing well, being still pink months afterward and I started taking 4000 IU of retinol in cod liver oil for this. My skin gradually improved and now actually looks younger and my lower back pain soreness after running started to improve and improved further with an increase to 8000 IU of retinol. Long story short…After trials with higher doses I settled on 27,000 IU as optimal (higher doses gave dry eyes). The 10,000 IU D3 to 27,000 A ratio seems to work for me (I’m 95 kg) but it would be even better to see research supporting this. Is there any good science you have found on this question of the ratio?-
6.1
Good for you, David! Indeed, I am not aware of any research on the optimal balance. And even if there were, we don’t have a way of taking account of the other sources (vs. just supplements)… Some individuals take in copious fully-formed vitamin A from foods (e.g. liver, egg yolks). Others don’t but are champion converters of beta carotene to Vitamin A. Some make final form Vitamin D readily, wile others don’t. Some have stronger Vitamin D receptor sensitivity while others don’t (and genetics can play a role here). It’s a very rich, complex mix, and there is no substitute for getting educated, following your intuition, exploring your own experience, and paying close attention to how your body responds. I would just keep in mind that Vitamin K is the third member of this trio too. If you are supplementing with the others at these high levels, I personally would consider some additional K2 (in the MK-7 or MK4 form). This is an exploratory write-up that I think you may enjoy: https://www.westonaprice.org/health-topics/abcs-of-nutrition/update-on-vitamins-a-and-d/ . Be well!
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6.2
Indeed, I certainly would agree with you that there is confusion and much more to learn about the benefits of MK-4 vs. MK-7 supplementation and optimal choices for various purposes. I didn’t share the article to imply this was “the right answer” at all, just to share more information and food for thought with regard to speculation on optimal ratios. Clearly you are well read on the topic, and most of all, I appreciate your deep review of the research and skeptical eye.
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I have case of documented severe vitamin A deficiency (via labs), despite animal intake and trial of Green Pastures fermented cod liver oil AND trial of Vital Proteins grass fed beef liver capsules, (labs show vitamin A continuing to decline despite these). How long do you recommend supplementing with actual vitamin A/retinyl palmitate before re-testing? Hashimoto’s is part of the picture, inhibiting conversion from beta carotene, but near normal antibodies and ideal thyroid labs, including Free T4, Free T3 and Reverse T3.
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5.1
Indeed, there may be poor conversion, as you well state. However, given the ongoing intake of these sources of Vitamin A, I would consider the likelihood of fat malabsorption in the intestines (perhaps combined with fat maldigestion e.g. low lipase secondary to poor pancreatic output and/or low bile output usually secondary to congestion in the bile duct system). And indeed a hypothyroid state can contribute to suboptimal digestive secretions in a circular, debilitating fashion. For you personally, this seems unlikely given your thyroid panel results (though the impact can be erratic). You certainly could supplement with retinol palmitate for six weeks (what I would choose as well – toward the goal of prioritizing getting the body in an optimal place, especially if there are B/L chronic autoimmune activation concerns) and then retest to help differentiate between gut dysfunction and poor conversion.
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4
Tracy,
Are there any foods (coffee included, drugs, or lifestyle habits that wipe out Vitamin A in the body?
Thanks.
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4.1
Well, first of all, I would reference explicit items implied by the article above. Excessive Vitamin D intake can deplete Vitamin A. Chronic stress (high cortisol) that impairs conversion of T4 to T3 thyroid hormone is also a harmful choice in this vein given its potential impact on poor beta carotene conversion; choices that create physiological stress (e.g. eating of one’s food sensitivities, ongoing insufficient sleep) would do the same. Having poor fat absorption in the gut will also have an impact (e.g. those without a gallbladder, persistent diarrhea, overuse of laxatives). There are only a few drugs of known impact e.g. http://pennstatehershey.adam.com/content.aspx?productId=107&pid=33&gid=000716 . I am not aware of any study explicitly looking at the impact of coffee, though a negative effect has not been found wrt other fat-soluble vitamins; of course, if coffee causes diarrhea or excessive transit time, then the vitamin may be negatively affected simply due to malabsorption.
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Dawn says:
Thank you. I have an account with Pure Encapsulations so that recommendation is perfect. I am not familiar with vitamin A acetate. How does that differ from retinyl palmitate?
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3.1
Two different forms of Vitamin A. And semantics. Retinyl (or “retinol” or “Vitamin A”) palmitate or retinyl acetate. Chemically, they are ester forms of retinol. Pure retinol is easily oxidized and needs a stabilizer for supplement manufacture. This may be of interest to you for further learning: http://lpi.oregonstate.edu/mic/vitamins/vitamin-A .
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Do you have a specific vitamin A supplement to recommend? Most of my clients have autoimmunity (especially Hashimoto’s) and digestive issues so ones that would be good for those situations would be helpful.
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2.1
There are many excellent choices. I have often recommended Pure Encapsulations Vitamin A plus Carotenoids: http://www.pureencapsulations.com/vitamin-a-carotenoids.html. This gives a 5000 IU dose of fully-formed Vitamin A along with other key antioxidant carotenoids (good for countering all oxidative stress, though particularly helpful for eye health). Especially for those with digestion/absorption limitations (and those with chronic AI also often have sensitivities/allergies), I am a fan of Pure Encapsulations and Thorne Research. Two brands certified gluten-free and which contain no binders or fillers at all in any of their products. Typically more expensive but worth it, given you want to be confident that the nutrient in question is actually being absorbed and put to good use!
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Tracy, I am just wondering why on the EWG skindeep website, when you type retinol, they consider it toxic. Isn’t retinol Vitamin A. It is an 8 in toxicity there. Thanks.
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1.1
Yes, I can see how this might be confusing. While Vitamin A within the body is a necessary vitamin, the article correctly points out that excessive Vitamin A (as is true with every fat-soluble vitamin) can be harmful. It also highlights that Vitamin A used on the skin (topically, as opposed to ingested internally) and then exposed to sunlight is vulnerable to free-radical damage (which can be harmful). Again, this is true of many nutrients and is why most good-quality supplements will have antioxidants added to their formulations to protect the raw ingredients from the damaging effects of sunlight, air, and oxygen – even when designed for internal consumption. Most high-quality skin creams I have seen including retinol for purposes of skin healing will specifically warn the consumer not to expose themselves to direct sunlight right afterward. I think this is good guidance.
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Managing a busy household requires constant energy. I’ve been taking a Vitamin B complex, but the Vitamin A details are eye-opening. How do you see the combination of Vitamin B complex and Vitamin A benefiting individuals like me who juggle family responsibilities and need sustained energy and immune support?