Vitamin A is an incredibly important vitamin to humans and is even more important to consume adequate amounts during your prenatal to postnatal journey and beyond. However, despire the importance of this vitamin, there seems to be alot of scarcity or fear around its use during this important time. This fear seems to stem from a study conducted in 1995 which showed that synthetic vitamin A caused an increase in birth defects.
However, this study had many flaws and many studies following it have disproven and even shown contradictory evidence. Is this article we will go over the distinction you should make between synthetic vitamin A and natural vitamin A, the flaws of this 1995 study, the risks with not getting enough vitamin A during pregnancy and solutions.
Understanding Vitamin A
There is often a lot of confusion when it comes to Vitamin A. It is an essential fat soluble vitamin which means that it is often best absorbed in the presence of fat.
Your body gets vitamin A in two main ways. The first is by consuming preformed vitamin A (retinol) which is the most bioavailable form. You will find this exclusively in wholefood animal products like beef liver, eggs and fish. The second way is through provitamin A (carotenoids like beta carotene). You will find this mostly in fruits and vegetables. Beta Carotene needs to be converted in the body to form Vitamin A.
It is important to note that many people on a plant based diet think they can get an adequate amount of vitamin A through eating enough plants and fruits rich in beta carotene. However, while this might be true for a large percentage of people, this is not the case for everyone. This is because up to 42% of people carry the BCMO1 gene mutation which makes it difficult to convert beta carotene into active vitamin A (1)(2). This is why many plant based eaters can be deficient in vitamin A without knowing why.
Regardless of your dietary pattern of eating, the population in general seems to be largely deficient in this essential fat soluble vitamin. For instance, it is estimated that over 124 million children are vitamin A deficient (3). Globally, this might equate to 30% of children (4). Vitamin A deficiency is not just a concern for children but also adults with statistics suggesting adults consume less vitamin A than young children (5).
Synthetic Vitamin A v Natural Vitamin A
The difference between natural vitamin A and synthetic vitamin A is one of the biggest oversights that health professionals overlook. Synthetic vitamin A and natural vitamin A are not the same and close to 95% of research has studied only synthetic forms.
As already mentioned, you can get natural vitamin A through two ways. By consuming either preformed vitamin A from animals products like beef liver, organ meats, eggs and fish or by converting beta carotene from fruits and vegetables into active vitamin A.
Synthetic vitamin A on the other hand is usually a vinyl or coal tar at one stage during processing. You will typically find it as reinyl acetate or retinyl palmitate in supplements. You might also find synthetic beta carotene in certain supplements. It is manufactured from benzene, which is often extracted crude oil.
The Risks of Not Getting Adequate Vitamin A For Pregnant Women
Oftentimes, many women will be told of the risks associated with supplementing with too much vitamin A but will rarely be advised about the risks of not getting enough vitamin A during this important period. This can have the effect where women come to fear vitamin A consumption entirely and consume less of it. The other overlooked part of vitamin intake during pregnancy is that the vitamin A requirements for mothers go up during this time, specifically in the third trimester where stores are being transferred to baby (6). Low consumption can not only increase your babies risk of health complications but can also impact a mums health.
Increased Maternal Mortality & Night Blindness
In fact, a vitamin A deficiency (VAD) during pregnancy is associated with an increase in maternal mortaility (7). In severe cases of VAD which is often seen in low income families or families in developing countries, maternal night blindness was associated with a 3-fold excess risk of maternal death (8).
Increased Maternal Mortality & Maternal Anaemia
However, one of the biggest risk factors for pregnant mums has to do with maternal anemia, which is a common consequence of VAD. According to statistics, maternal anaemia impacts 41.8% of women globally and increases (9) (10). Even subclinical levels of vitamin A have been associated with maternal anemia, particularly in the third trimester (11). Subclinical just means that your levels are on the low end of normal. This would make sense because nutrient stores in mums are depleted most during the third trimester and levels on the low-normal end will typically fall into the deficient zone.
Increased Risk For Multiple Health Concerns
Outside of pregnancy specific concerns, VAD generally has been connected with a host of health concerns including inflammatory conditions, skin issues, poor immune health, vision concerns, infertility, plus more (12)(13)(14)(15)(16).
So do not overlook the importance of vitamin A for mums aswell as their baby as there are risk for not consuming enough vitamin A for both parties.
The Risks of Not Getting Adequate Vitamin A For Baby
Many people will point to birth defects as the main reason to be wary of vitamin A during pregnancy. While you should not be downing vitamin A like candy, there is more solid evidence that not getting enough vitamin A during pregnancy can lead to birth defects and developmental concerns in infants.
Congenital Diaphragmatic Hernia (CDH)
While vitamin A deficiency has been linked to a number of birth defects, the one which has been studied the most and is not often talked about is Congenital diaphragmatic Hernia (CDH). CDH occurs when the diaphragm fails to close during the prenatal period, allowing the contents of the abdomen to migrate into the chest, preventing the growth and development of the respiratory system. CDH is the greatest cause of respiratory failure in infants and accounts for 8% of congenital anomalies (17)(18).
The connection began in the early 2000s when researchers coined the retinoid hypothesis for CDH which was based on circumstantial and direct experience evidence (19). Since then, several studies have found and continue to find evidence that a Vitamin A deficiency might be the primary driver of this congenital defect.
Most recently, a 2022 animal study found that pregnant mice fed a low vitamin A diet over a 3 month period, lead to an increased incidence of CDH in mice, providing evidence for the retinoid hypothesis (20). This was the first study which showed that manipulating dietary intake of vitamin A strongly induced CDH in offspring.
This study supports two recent epidemiological studies in humans which have found that a low dietary intake of vitamin A during pregnancy was strongly correlated with CDH in humans (21)(22). Infants with CDH have also been shown to have low circulating levels of vitamin A (23)(24). Other studies also provide evidence for the link between vitamin A and CDH (25)(26).
CDH is not the only birth defect associated with a VAD. There are also many developmental concerns linked with not getting enough vitamin A.
Abnormal Pancreas Development Risk
Outside of CDH, VAD has also been connected with multiple variations of other birth defects. For example, animal studies have shown that VAD during pregnancy can impact the development of the pancreas in rats, potentially connecting VAD to the onset of diabetes in infants, adulthood and beyond (27)(28).
Abnormal Auditory Development Risk
Likewise, other animal studies have also shown that a VAD during pregnancy may lead to the abnormal development of the inner ear in infants (29)(30)(31). Based on these findings, researchers believe that adequate levels of vitamin a during pregnancy might offset the risk of sensorineural hearing loss in humans (32).
Abnormal Kidney Development Risk
VAD also has links with poor kidney development. In study, it was found that mild VAD led to a decrease in kidney weight and nephron numbers in newborns (33). Another study conducted on 16 mothers with VAD and 64 mothers with sufficient Vitamin A found that infants born to VAD mothers had smaller kidneys compared to infants born to mums with sufficient vitamin A (34). A systematic review also found an association between VAD during pregnancy and poor kidney function and structure in children (35).
Abnormal Congenital Spinal Deformities Risk
In one animal study where they manipulate dietary intake of vitamin A from preconception to birth, it was found that a VAD led to an increased risk of congenital scoliosis by 13.79% compared to the 0% risk in control group who were fed a normal diet during this time (36). The researchers concluded that a VAD impacted retinoid signalling pathways leading to defects.
Abnormal Anorectal Malformation Risk
In other animal studies looking at VAD, researchers have found that inadequate vitamin A during pregnancy may lead to embryonic development of anaorectal malformations in offspring (37).
Aside from VAD risk and birth defects, not getting enough vitamin A has also been connected with other conditions.
Increased Risk Of Childhood Schizophrenia
VAD, especially during the second trimester, was found to be connected with a 3x increase in the risk of developing a schizophrenia spectrum disorder in a large study looking at 19,044 births (38).
OKAY, But Doesn’t Excessive Vitamin A Also Cause Birth Defects?
The vast majority of fear and caution comes from a study conducted in 1995. Since then, this study has left a lasting imprint on vitamin A guidelines and how health professionals choose to navigate vitamin A recommendations during pregnancy.
The 1995 Study Summary:
In this study, the researchers main conclusion was that infants were at an increased risk of birth defects when the pregnant woman's intake exceeded more than 10,000IU per day in supplemental Vitamin A (39). This study had a few flaws however and since its publication, multiple other studies have shown conflicting results, with some even showing that 10,000IU daily is not just safe but may even be indicated for preventing birth defects.
Issue 1: ‘Normal’ Birth Defects Normally Occur At 3%
The conclusion of this study was that “high dietary intake of preformed vitamin A appears to be teratogenic. Among the babies born to women who took more than 10,000 IU of preformed vitamin A per day in the form of supplements, we estimate that about 1 infant in 57 had a malformation attributable to the supplement”. However, according to the CDC, 3% of births, which is around 1 in 33 births, are likely to result in a birth defect (40). Technically, you could say that the study had a protective effect based on ‘normal’ defect rates and the studies' conclusion.
Issue 2: The Conclusion Was Based Off Synthetic Vitamin A Intake
The conclusion surrounding the 10,000IU threshold was based purely on the synthetic form of vitamin A, not the natural food complex vitamin A. The majority of studies looking at vitamin A toxicity usually research the synthetic form and not food based vitamin A. They are not the same. Synthetic vitamin A is an isolated compound devoid of cofactors, minerals and other compounds which assist in the utilisation and biocompatibility of natural vitamin A. While this study did consider food based vitamin A and did see an increased prevalence in birth defects, the amount of women consuming above 10,000IU was so few, that it made “birth defect estimates from food imprecise” and some prevalence ratios “statistically unstable”.
Issue 3: No Distinction Made Between Synthetic A, Fortified A and Natural A
The study also failed to distinguish between fortified foods which contained synthetic vitamin A and wholefood sources of vitamin A like liver, eggs and fish. Given fortified food cereals are full of sugar, pesticide residues, artificial colours, additives and preservatives, it would make sense that you might see an increase in birth defects for people consuming large amounts of these foods. For instance, certain diets like the western or vegetarian diet have been connected with an increased risk for birth defects (41)(42).
Issue 4: Vitamin A Status Was Determined By Questionnaire
This study also used food based questionnaires for measuring vitamin A consumption, rather than doing blood work and testing vitamin A status. For example, what did you eat last Monday? In questionnaire or survey based studies, there is the potential for both demand and recall bias where participants change their behaviour by simply being in the study or cannot accurately recall information.
Issue 5: A 1990 Study Found The Opposite
Before we jump into the post 1995 studies, one study with similar methods found that daily supplementation up to 40,000IU actually reduced the risk of birth defects by 50% compared to no supplementation. While amounts over 40,000IU increased the risk of birth defects by 2.7% (43). So yes, there might be a risk, but at levels greater than 10,000IU as concluded by the study.
What Has Research Post 1995 Shown?
Since the publication of the 1995 study, several studies have provided evidence contradicting the results. Again, it is important to note that these studies mainly looked at synthetic vitamin A and not food based.
1998 Study: “Periconceptional vitamin A use: how much is teratogenic?”
In this study, the researchers stated that no human epidemiological studies establish at what level vitamin A becomes teratogenic (44). However, the study did present data based on blood tests that showed that women taking 30,000IU of preformed vitamin A daily, were not greater than the retinoid blood levels in pregnant women during the first trimester who delivered healthy babies. The researchers also reference non human primate data showing no teratogenicity of vitamin A at doses of 30,000 IU/d. They state that if periconceptual levels up to 30,000IU occur unintentionally, animal studies support only a very low risk of teratogenicity. Based on this study, it seems that vitamin A consumption at doses up to 30,000IU present only a low risk of causing issues.
1998 Study: “Safety of vitamin A: recent results”
Again, the researchers in this study stated that the available data (1995 study) cannot convincingly define an upper safe limit for periconceptional vitamin A intake (45). In this study, researchers who evaluated blood levels of vitamin A in pregnant women found that doses of 30,000IU per day resulted in healthy blood levels of vitamin A and had no association with teratogenicity.
1999 Study: “High vitamin A intake in early pregnancy and major malformations”
In this study, 311 mothers consumed between 10,000IU-300,000IU of vitamin A during the first trimester of pregnancy with the median dose being 50,000IU (46). This study found no congenital malformations among the 120 infants exposed to more than 50,000IU of vitamin A per day.
What Can We Learn From These Studies?
Based on the overall research it seems that evidence supports intake of vitamin A of 10,000IU for protective benefit against birth defects. Of course, best practice is to always consult with your health care professional and even request to test your vitamin A status. From there, you can tailor your diet to suit your needs.
From the evidence we also know that any birth defects related to excess vitamin A, relate mainly to the synthetic form of the vitamin and not the natural food based vitamin A (not including fortified foods made with synthetic vitamin A).
Why Is Food Based Vitamin A Supreme?
The problem with nutritional studies is that they tend to study specific vitamins and nutrients in isolation and in the absence of other nutrients and cofactors. This is not just an issue with nutrition studies but medicine generally. For example, vitamin A is never found in isolation in foods like liver, eggs and fish. It is always found alongside other nutrients which help absorption, utilisation and minimise the risk of toxicity.
For example, Vitamin E, Taurine, cholestrol and Vitamin K have been shown to reduce vitamin A toxicity (47) (48) (49) (50).
However, when we study nutrients like vitamin A in isolation and disconnect them from nature, it makes sense that we might find adverse results. Humans were never supposed to consume single forms of nutrients from artificial sources.
Of course, this is not to say that you cannot overdo it with vitamin A from food because you definitely can but as is with any food, balance and moderation is key.
Vitamin A Trade Off: A Summary
Based on the research, there is far more ‘good evidence’ that consuming too little natural vitamin A can increase your baby's risk of birth defects than consuming too much vitamin A.
In Vitamin A deficiency studies, they directly manipulated vitamin A intake (e.g. they gave rats low vitamin A to see the impact versus a normal diet).
In comparison, it is not ethically feasible to manipulate vitamin A intake in humans which is why vitamin A toxicity studies mostly look at observational studies or make inferences from blood tests.
Always consult with your health care professional when making any dietary changes during your pre to postnatal period. They can help dial in a nutritional plan optimal to your unique situation and health situation.
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