May 10, 2018

When Carrots Don't Cut It: Your Genes and Vitamin A

Quick Summary: Beta-Carotene is the most abundant type of Vitamin A in the plant kingdom. But, in order to use Beta-Carotene, our bodies have to convert it to retinol, the active form of vitamin A.

Common variations in the BCO1 gene can create much lower conversion rates and thus lower levels of bioavailable vitamin A from person to person. This may contribute to why some people have difficulty maintaining a vegan diet for extended periods of time.

Severe Vitamin A deficiency is rare in the developed world, but minor deficiencies often have no symptoms other than fatigue. Chronic alcohol intake depletes retinol. Liver, eggs, dairy, fish, and chicken are the top sources of active retinol.

Image result for carrots picture


What Forms Does Vitamin A Come In?


We're used to thinking of Vitamin A as Beta-Carotene. That's the type of Vitamin A that's found in carrots and other plants. Vitamin A comes in two main forms: Retinoids and Carotenoids. But, the carotenoids like beta-carotene are technically provitamin A, because they are converted into the actual bioavailable form we use called retinol.

A simple way to think about it is that only retinoids are found in animals. Plants produce only carotenoids. While beta-carotene is the most abundant in our diets, there are a number of other carotenoids that can be converted to retinol. Some of them, such as anaxathin, lutein, or lycopene also have specific antioxidant properties. In general, foods that are orange or yellow in color contain carotenoids.

For the remainder of this article, when I say vitamin A in reference to it's action in the body, you can assume I'm talking about retinol, the bio-available form of vitamin A. I'll refer to beta-carotene specifically by name.


First of all, what does Vitamin A do?


An essential nutrient for your brain, immune system, skin, eyes, teeth, bones and for the synthesis of hormones, Vitamin A/Retinol was first officially named in 1920. Before this, scientists were aware of 'unsuspected dietetic factors' in milk that had been show to promote growth in rats for roughly 100 years prior. Warning: This next section is a little bit technical, so if the jargon doesn't make sense, I'll get back to non-sciencey language in the next section.


Vitamin A Is Essential For Vitamin D and Thyroid Hormone


Vitamin A/Retinol is essential for activating RXR (retinoid X) receptors and RAR (retinoid R) receptors. These receptors form "pairs" (called dimers) with both the vitamin D receptor and Thyroid Receptors that allow them to function properly. If you are vitamin A deficient, you can take all the vitamin D you want and it will have little effect. Both RXR's and RAR's are also DNA transcription factors, so they impact your ability to modulate genetic expression as well.

So, if you're taking vitamin D and your not getting the results you want, adding vitamin A may help.


RXR combines with the Vitamin D Receptor (VDR) to receive 1,25(OH) Vitamin D


VItamin A is Essential For Hormone Production 


Pregnenolone is the main precursor to steroid hormones in your body and your body builds it out of LDL cholesterol, vitamin A, and T3 thyroid hormone. So, low pregnenalone or other hormones that are made from it could be linked to low vitamin A.


Vitamin A Influences the Immune System


Vitamin A shifts the immune system from TH1 to TH2 type cells. While this is a complex topic, TH1 dominance tends to occur in autoimmune conditions and tends to correlate with hyperactive immunity. This is especially important for gut and intestinal health, as the gut and immune system are intricately related with each other.

Vitamin A also helps increase the production of T-Regulatory cells with are essential for keeping the immune system in balance. (Reference)


The Brain and Vitamin A


Vitamin A/Retinol plays a central role in increasing neuroplasticity and neurogenesis. It’s critical to our hippocampus and hypothalamus, which controls memory and wakefulness, respectively [Reference]. It's also important for long-term potentiation (LTP), which is important to form memories [R]. Vitamin A deficiency also causes circadian disruption, which then can cause cognitive dysfunction.


Vitamin A and Circadian Rhythm


If you've followed my blog for a while, you know I'm huge on circadian rhythm. Low vitamin A status causes your circadian clock to malfunction, as the RAR's and RXR's I talked about earlier are involved in the expression of circadian clock genes. In rats, Vitamin A deficiency has been show to essentially abolish the expression of the PER1 gene, a major regulator of your circiadian biology. Without properly timed circadian rhythm, a whole host of negative health consequences are more likely to manifest. [Reference] If you'd like to learn more about circadian rhythm in general, you can check other my blog posts about it here, here, and here.

Furthermore, Vitamin A is essential to the function of the suprachiasmatic nucleus in the brain, which is known as the "central clock" in the body. The study referenced here refers to Vitamin A/Retinol as "mediators of rhythm in the brain."


Vitamin A and Insulin


Vitamin A is also essential to function of beta-cells in the pancreas, which are responsible for the release of insulin in response to blood glucose levels. [Reference]


Image result for vitamin A and bco1


How do we make Retinol?


Our bodies convert beta-carotene into retinol through the Beta-Carotene Oxygenase 1 (BCO1) enzyme. When beta-carotene comes into contact with this molecule in our bodies, it is transformed into the usable form. Roughly 95% of retinoids arising from beta-carotene are produced by the BCO1 pathway, making it exceptionally important for vitamin metabolism. But here's the deal: Some people have a more or less functional BCO1 gene. This means some people convert very little beta-carotene into usable retinol.


Genetic Variations


People that carry the T allele in either of two identified coding SNPs in the BCMO1 gene have roughly a 32% lower ability to convert beta carotene into retinol. Those with T alleles in both SNPs have about a 69% lowered ability to convert beta carotene into retinol and an increased plasma beta carotene concentration due to the lowered conversion. [Reference]

For a full primer on what a SNP is and how to use them, see my article here.

If you have your 23andMe data, you can look up the following SNPs. T is the risk allele for both.

rs12934922 and rs7501331

And, beyond those variations, there are several SNPs outside the coding region of the gene, known as "promoter SNPs" which further impact how much of the BCO1 enzyme your body makes. [Reference] The exact function of these SNPs isn't known, but the G allele of rs11645428 and A allele of rs6420424 are known to further reduce conversion each by about 50%.

So, with compounding SNPs, it seems that at least a portion of the population is at risk for poor beta-carotene conversion.


Other Health Factors


Other factors that can impact low vitamin A status include poor bile production, too little fat in the diet (Vitamin A is a fat soluble vitamin and requires dietary fat to absorb) and an abnormal circadian rhythm.

Certain people predisposed to true Vitamin A deficiency include:

  • People with illnesses affecting the way food is absorbed from the gut (bowel) into the body, such as:
    • Coeliac disease.
    • Crohn's disease.
    • Cystic fibrosis.
    • Some diseases affecting the liver or pancreas.
  • People who have a strict vegan diet
  • Alcoholics
  • Some long term prescription drug users
  • Children in poverty and developing countries

And here are symptoms associated with low vitamin A status:

  • Fatigue
  • Bad night vision
  • Vision problems in general
  • Negative effects from the sun
  • Skin problems
  • Hair Thinning/Falling Out
  • Brittle teeth/Nails
  • Infections, including throat and chest infections, and gastroenteritis.
  • Infertility.
  • Miscarriage.
  • High LDL Cholesterol

What to do if I have these SNPs?


So, if you have these SNPs, getting extra retinol in your diet is important.

Realistically, if you have just one of those SNPs showing lower conversion, you probably don't have to worry too much about it, but if you have multiple low functioning SNPs stacked on top of each other, or have low functioning SNPs and meet any of the risk factors listed above, you might be wise to consider adding in a source of retinol to your diet. You can get retinol in supplemental form, and it is often listed as palmitate in a multivitamin. Or, consider eating liver or eggs or taking desiccated liver capsules.

In general, if you can get vitamin A from your food, do that before taking a supplement. 

Here's a list of top retinol sources:

"One of the best sources of retinol is beef liver, which has 4,208 micrograms in a 3-ounce serving. The next highest sources, eggs and dairy products, drop down to 80 micrograms in a large egg, 66 micrograms in 1 cup of 2 percent milk and 60 to 72 micrograms in 1-ounce of most cheeses, such as cheddar, Swiss and Parmesan. A 3-ounce serving of shrimp has 46 micrograms, while salmon, flounder and chicken breast are in the range of 6 to 10 micrograms per 3-ounce serving. You'll only get 2 micrograms of retinol from the same portion of light-meat turkey or roast beef." [Reference]


Image result for liver pate

Liver is an acquired taste but one of the best sources of retinol.


It's important to note that you can take too much vitamin A in the retinol form, so don't oversupplement. And, you only need to eat about liver once a week (only if you like it) because it is so high in retinol comparatively to other sources. The human body actually stores most of it's retinol in the liver as well. Typically, amounts in most multivitamins aren't going to cause an excess but it is a good idea to get a balance between retinol and provitamin A forms.

Here's a chart looking at the upper limits of retinol intake. It's advised not to intake levels beyond these.

Also, vitamin A/retinol competes with vitamin D and vitamin K2, so if supplement with A you should generally also supplement with D and K2 to keep things balanced.


Vegans take note.


Is it possible to get enough retinol on a Vegan diet? Sure, but a a low conversion status makes it more difficult. Most healthy vegan diets (i.e. that focus on vegetables and not vegan mac n cheese and soy everything) are high enough in beta-carotene that even with a moderately lowered conversion status you're likely getting enough. However, it's well known that strict adherence to veganism in the long run can create health issues in certain people. Eating vegan works amazingly for some people, but there's quite a bit of speculation from the health community that these SNPs could play a role in have difficulty with vegan diets in the long run. This is much less of a problem for vegetarians that consume dairy or eggs since those both contain retinol.

Chris Masterjohn, a well-known health expert and nutritionist, is a good anectdotal example of this. He was vegan for a number of years in his teens and twenties and after realizing he was symptoms of vitamin A deficiency, began eating liver, and was so amazed with his health turnaround he ended up doing his PhD dissertation on Vitamin A. He's contributed tremendously to the field but he's a classic example of someone trying to eat a "healthy" diet that simply wasn't matched well with his biology.

From an ancestral health perspective, the way most people eat only the muscle meat of an animal today was not how our forebearers ate meat. The liver was always consumed along with other organs, leading to higher consumption of retinol than most meat eaters today get.


Fine Vs Optimal


While severe Vitamin A deficiency is rare in the developed world, getting enough doesn't mean you're getting the optimal amount. There are degrees of health, not just "you're sick" or "you're fine". If you're a low converter, dialing in the right amount of retinol in your diet could help make the difference between fine and great. 

Mild Vitamin A deficiency often has no symptoms apart from fatigue. This is especially true for people with BCO1 polymorphisms.


Individual Metabolism = Individual Dietary Needs


When I was researching this, I came across a video from a very angry vegan claiming this research was invalid, funded by meat supporters, and "anti-vegan spin." Let me be clearn, I'm not opposed to vegan diets, I think they work great for certain people. But, I am opposed to people claiming that veganism is right for everyone the same way I'm opposed to claiming everyone should eat meat. In the video, he made the point that severe problems with this are probably found in less than 5% of the population. But, isn't that the point of real nutrition? If there is a portion of the population that does poorly with something, we owe it to them to NOT ignore them and say they don't matter. I'm not sure what the actual percentage of poor vitamin converters are out there, but rejecting this data because it throws a wrench in your diet dogma doesn't sit well with me.

In my opinion, this information is great common ground to understand why vegan diets don't work for everyone all the time, and an excellent way to illustrate the biological differences we have. Personally, I find these differences to be a point of compassion for understanding why people make different choices for their body. Dogma and diet don't mix in real life. 

And, if you are vegan, I think this is essential information to incorporate into your understanding of how to get the most out of your nutrition.


Final Thoughts  


So, check out what BCO1 genes you have and consider doing some lab testing to assess your vitamin A status if you suspect you have a deficiency. The bottom line is that although Vitamin A deficiency is rare, low converters are more likely to experience issues. If you're experiencing issues with energy, skin, eyesight, or hair, especially if you're vegan, you may be in need of more retinol.


May your carrots be vibrant and your liver palatable.


Want to optimize your health? I look at hundreds of genes like BCO1 that can help guide you in the right nutritional direction.  Send me a message and we'll set up a free 30 minute consultation and discuss how to make your goals become reality.




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