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Vitamin A Carotenoids and Beta Carotene

Implications for health

vitamin-A-absorption-metabolism.jpg

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Vitamin-A-Carotenoids-Metabolism (Graphic above)

Intake from foods

This is either from:

  1. Preformed Vitamin-A obtained from animal sources - the major from of which is an ester and predominantly retinyl palmitate. This will then be converted to retinol and retinyl esters.

  1. Provitamin- A from plant sources - these are the carotenoids that have to be converted to vitamin-A (retinal) and only 4 are provitamin-A carotenoids out of the 600 known carotenoids produced by plants, algae and photosynthetic bacteriaLPI: alpha-carotene, beta-carotene, gamma-carotene; and the xanthophyll beta-cryptoxanthin (all of these contain beta-ionone rings) can be conveted to retinal. Retinal can then be converted to retinol and retinoic acid (RA).

Some important facts on vitamin-A

  • Approximately 50-85% of total body retinol is stored in the liver and more than 90% of this as retinyl esters (RE)157

  • Retinal plays an important part in vision – it is a structural component of rhodopsin or visual purple, which is the light sensitive pigment within rod and cone cells of the retina.

  • Retinoic acid (RA) affects the transcription of many genes158

  • Without enough protein and amino acids, transport proteins such as RBP or TTR (Transthyretin) cannot be formed and thus retinol cannot be transported. So Protein Energy Malnutrition is of concern in developed and developing countries as a cause of Vitamin-A deficiency. Up to 65% of patients in hospital could be malnourished220,222 and it has been estimated that around 33% of people over 65 years of age in the US and UK eat a diet that is deficient in both protein and calories221. This places such an individual at great risk for sepsis (infection) and increased morbidity and mortality. The British Association of Parenteral and Enteral Nutrition (BAPEN), estimates 10,000 lives could be saved if the possibility of malnutrition was actively assessed at the time of admission and then corrected221,223. A significant protein energy malnutrition will worsen a pre-existing vitamin-A deficiency putting the patient at high risk for an infective complication. All of this is worsened because any acute illness or surgical intervention will increase the need for nutritional resources greatly in an individual already depleted of nutritional resources.The triage theory of nutritional resource deployment in times of scarcity, will be working overtime - the end result, a greatly weakened individual.

  • TTR is a retinol transport protein given the initials TTR because it transports thyroxine and retinol.

  • Retinoic Acid (RA) is the most potent metabolite of Vitamin-A159 (p305)

  • Esterified retinol is the form found in greatest concentrations in most tissues159(p311)

Vitamin-A and immunity:

Vitamin-A deficiency is regarded as a
nutritionally-acquired immunodeficiency disorder!

  • The following statement pretty well sums up how critical Vitamin-A is to the immune system:

    "...no micronutrient deficiency is more synergistic with infection than that
    of vitamin A’ (Scrimshaw et al. 1968)188."

  • Hopefully the headline above says it all - that Vitamin-A deficiency is a nutritionally-acquired, immunodeficiency disorder - is summed up in the following quote:

    "Vitamin A deficiency is a nutritionally-acquired immunodeficiency disorder characterized by widespread pathological alterations of mucosal epithelia of the respiratory, gastrointestinal, and genito-urinary tracts, impaired antibody responses to protein antigens, altered cell-mediated immunity, and alterations in T-cell subsets188."

  • Longitudinal studies in preschool children demonstrated that even mild Vitamin-A deficiency could lead to respiratory and diarrhoeal disease and increased mortality188.

Redundant arguments

  • It is a pointless argument that individuals should not supplement if this is necessary to ensure an optimal level of Vitamin-A in the body.

  • There are always going to be pros and cons to the use of either a supplement or a pharmaceutical item so it comes down to the use of a nutraceutical (or pharmaceutical), within the context of an individual's clinical history.

  • The Hunter-Gatherer had staggering levels of the fat soluble vitamins A, D, E and K
Vitamin % RDA* Comment
A 858%
D 0 Negligible levels in everyday food (adequate sunshine or supplements needed)
E 331%
K 1,454%
*The Paleo Diet Revised Edition - Loren Cordain

  • That a healthy intake of fat soluble vitamins is vital for optimal health can be seen from the figures in the table above which has been determined from studying the of food intakes of the many hunter-gatherer tribes that have existed but are now extinct and the relatively few that still exist on the planet today.

  • The hunter-gatherer would have been able to synthesize significant amounts of Vitamin-D from cholesterol through sun exposure. Lack of sun exposure due to the use of sunscreens, clothing and working indoors therefore not having the opportunity to get sufficient sunshine is ensuring large population numbers in the Western world suffer Vitamin-D deficiencies. See the QuickGuide on Vitamin-D - Click here

  • Using the evolutionary template to try to understand what we should and should not eat, seems to be a fundamental principle we should all embrace. That evolution is dynamic and that adaptations can occur to more recently introduced food groups such as grains or dairy, is a weak argument against the premise of Dr. S. Boyd Eaton, that our genes determine our nutritional needs and that our genes were in turn shaped by evolutionary pressures including the limited, natural nutritional resources available over the aeons of human evolution.

  • Remember, to have reached this point of adaptation in a relatively short space of time over 10,000 years for grains and 5,000 years for dairy has wreaked untold misery for countless millions of people over this period of time where these poor wretched  individuals have reacted severely to either the gluten component within grains, or to the damaging effect of lectins or suffered from malnutrition due to phytate bound minerals in grains.

  • In the case of dairy,  countless millions suffered the misery of diarrhoeal disease due to lactose intolerance resulting in malabsorption, stunted growth, skeletal abnormalities and vast numbers dying before they had the ability to reproduce to enable those individuals with the lactase gene to survive and thrive through the ability to digest milk. I'm sure there is a mutation out there that will enable us to eat cheeseburgers 24/7 but at what cost?

  • In essence, we need to look back to our dietary intakes to know what we should be doing.

  • An important point though is that there is a synergy between the fat soluble vitamins that we are still learning about. To supplement one without supplementing the other is a recipe for disaster. For example, without enough Vitamin-D, Vitamin-A can be ineffective or perhaps even toxic and the liver is an important target for this toxicity. It is also important to understand that without enough Vitamin-A, Vitamin-D may be ineffective. It is a reciprocal relationship and this is important.
  • So does this mean do not supplement? Absolutely not. Many subgroups in the population such as the aged, obese, lower socioeconomic groups who make (or can only afford), the wrong choices and essentially a very large percentage of a population who have very poor intakes of fruit and vegetables, may need to supplement. We should not forget those that consume a very low fat diet in the misguided belief that this will be beneficial for weight problems. They may eat provitamin-A carotenoids, but if not enough fat is consumed with these. there will be very little absorption for conversion to Vitamin-A (remember carotenoids are fat-soluble as well). If Westerners do not eat the foods that contain preformed Vitamin-A, and then shun the provitamin-A carotenoids through fruit and vegetables, where does this leave them?  Let's not forget 3rd world countries where supplementation or fortification of food can save lives and decrease the risk of blindness.

  • Right-wing views on supplementation have no place in the argument. In fact this is disastrous and shows a distinct myopic view that can affect many lives unnecessarily. What the argument should be is that supplementation can be a critical adjunct to medical treatment and should only be undertaken by qualified professionals who can test for blood levels to ensure adequacy or toxicity of any given dose (no 'set-and-forget' mentality) and to supplement in the clinical context of that individual with follow-up. How many doctors do this? Unfortunately they are few and far between. This is more a product of training and a lack of understanding about nutrients in the pathophysiology of disease. Doctors do care and so do their patients who long for such guided information on all things related to nutrition and preventative healthcare. Perhaps the paradigm will shift in the not too distant future and institutions will include clinical nutrition as a part of the medical curriculum where nutrients are prescribed alongside pharmaceuticals and exercise in a big-picture approach to health and disease.

Vitamin-A-Carotenoids-Beta-Carotene

Vitamin A and primal intakes vs modern day dietary intakes

  • When traditional diets were studied in native populations consuming these diets rich in unprocessed natural foods, it was found that these diets were 10 times higher in Vitamin A and Vitamin D47.

  • The paleolithic diets of the hunter-gatherer were rich in beta-carotene from vegetables and fruit and beta-carotene is a precursor to Vitamin A. These provitamin-A foods were also rich in another fat-soluble vitamin, Vitamin-K  So the paleolithic diet and lifestyle provided an abundant quantity of ALL the fat-soluble vitamins - A, D, E and K.

  • When our ancient ancestors ate an animal, the organ meats were prized and for good reason as these were a rich source of omega-3 essential fatty acids and a multitude of micronutrients with the liver being a rich source of Vitamin A .

  • Vitamin A deficiency emerged after the agricultural revolution with increasing use of grains in the diet. Grains have no Vitamin A48.

  • A lack of Vitamin A will lead to a condition called 'xerophthalmia' which describes dry eyes. In its severe form, this can lead to blindness.This is a preventable disease where very inexpensive supplementation with Vitamin A can prevent this disease progressing to irreversible corneal ulceration.Up to 500,000 children become blind each year in developing countries due to malnourishment.

  • Night blindness is one of the first signs of Vitamin A deficiency.

The importance of zinc in vitamin-A sufficiency

  • Zinc deficiency often accompanies Vitamin A deficiency and this adds to the insult because zinc is needed to synthesize Retinol Binding Protein (RBP) a carrier protein required for Vitamin A transport49.

Concentration of beta-carotene in carrot juice vs raw carrots

Food Serving Beta-Carotene (mg)
Carrot Juice 1 cup (236 ml) 22
Carrot, Raw 1 Medium 5.1

Reference: LPI

  • It can be seen by the table above, that just 1 cup or 1 standard glass of  carrot juice, will supply a significant amount beta-carotene far beyond that of eating raw carrots.
  • The carotenoids are associated with proteins in the plant matrix and this lowers the bioavailability of these compounds.
  • Chopping, cooking and juicing disrupts this plant matrix thus increasing carotenoid bioavailability significantly .

Beta-carotene and Retinol Equivalents

  • In food, beta-carotene has 1/12th the activity of retinol which is pre-formed Vitamin-A
  • As a result, it would take 12 mcg (micrograms) of beta-carotene from foods to provide the equivalent of just 1 mcg (0.001 mg) of retinol. Reference: LPI

Conversion to Vitamin-A - A braking mechanism for safety

  • Vitamin-A can be toxic in high amounts and thus it is far safer to have preformed vitamin-A in recommended doses a few times a week and beta-carotene in the form of fruit and vegetable juices daily, finely chopping vegetables or pureeing the carotenoid-rich vegetable sources to increase provitamin-A carotenoid bioavailability. It is important to rotate your foods and not to have the same thing day-in and day-out due to the accumulation of compounds your body's CYP450 system cannot metabolize well. So always choose different sources of vegetables and fruit on a weekly basis and try not to have the same thing for 3 - 4 days to wash out any phytochemical you may have a problem metabolizing.

  • Many concentrated phytochemical products are in the marketplace that are rich in carotenoids and a multitude of other phytochemicals. Having these a few times a week may also be beneficial.

  • Carotenoids such as beta-carotene are regarded as safe as the body decreases the conversion of beta-carotene to retinal when the body has produced adequate amounts of Vitamin-A. The analogy is that of putting the brakes on a car to slow it down.


Beta-carotene - severe limitations in bioavailability

  • There are many arguments put forth that view vitamin-A intakes in a preformed state as being dangerous.

  • What is important to state is that both low or high vitamin-A intakes are associated with poor health. What is important is to have an adequate or optimal intake of vitamin-A as preformed vitamin-A.

  • Depending on carotenoid intake and bioconversion to vitamin-A may well result in suboptimal intakes of vitamin-A putting an individual at risk of infections, mucous membrane problems (sinusitis, dry eye, dry mouth, otitis media, bladder problems, lung infections and others) and possibly cancer and cardiovascular risk.

Responders vs nonresponders

  • However, there is great variability in the ability to absorb and covert beta-carotene and individuals are categorized as responders or nonresponders160 (poor absorption/conversion).

  • Far less nonresponders were noted if beta-carotene was emulsified in oil160. This makes sense as carotenoids are lipid soluble plant pigments165. I discussed above how very low fat diets impact on provitamin-A carotenoid absorption.

  • This may explain why there is such a problem with suboptimal vitamin-A levels in non-Western societies where the principal source of vitamin-A intake is in the form of Provitamin-A carotenoids (90%) and little animal fat161. For maximum absorption of carotenoids, fat needs to be consumed at the time of carotenoid consumption165. Only 3 - 5 grams of fat is needed to increase the bioavailability of carotenoidsLPI.

  • Dietary fibre can decrease the absorption of carotenoids and increase faecal excretion of these compounds165. Juicing once again offers this advantage of disrupting the food matrix and providing a carotenoid-rich mix (if the right fruit and vegetables are used), without the excess fibre to decrease bioavailability.

Gastric pH and carotenoid absorption

  • Having an adequate gastric acid response and a low enough pH enhances carotenoid bioavailability165. There is an increased risk of atrophic gastritis in the elderly population (~20%) resulting in lower gastric pH and in those taking antacids and powerful proton-pump inhibitors for problems like gastro-oesophageal reflux (GORD/GERD)

Gallbladder disease or cholecystectomy on carotenoid bioavailability

  • Carotenoid absorption is dependents upon not only fat in the meal, but also the presence of bile salts to create mixed micelles (bile salt emulsification of fats)

  • With a non-functioning gallbladder or perhaps surgical removal of the gallbladder for various reasons, absorption of carotenoids will be limited.

  • With rising rates of overweight and obesity in the Western world, gall bladder disease is not that uncommon.

Carotenoid absorption from fruit and vegetables far less than once thought

  • The other major problem with depending on carotenoids to form vitamin-A, is that the bioavailability of carotenoids is far less than was once thought. According to the United Nations University (UNU) article on vitamin-A in developing countries, the vitamin-A activity of vegetables was only 23% of what was assumed and in fruits, only 50% of what was assumed. The authors thus used a factor of five (5), to adjust previous figures of plant-based vitamin-A activity161.

  • The other big problem with depending on carotenoid intakes for vitamin-A sufficiency, is that almost 80% of low and middle income countries have low fruit and vegetable intakes144.

  • In one study among 23,699 adults in 16 US states sampled in a random-digit dialing telephone survey, only 20% of those surveyed consumed the recommended intakes of fruit and vegetables. An important factor in this study was that there was lower fruit and vegetable consumption in the young and uneducated168. This low population intake and socioeconomic variability has been shown in many surveys of Western populations with regard to fruit and vegetable intakes.

  • Thus many factors conspire against provitamin-A carotenoids as being a good source of vitamin-A in societies and a good reason not to depend on these but to look at the addition of preformed vitamin-A through the consumption of liver, oily fish and fish-liver oils.

Increasing bioavailability of provitamin-A carotenoids

  • It was also found that disrupting the food matrix which is a critical bioavailability factor, could significantly increase the bioavailability of the carotenoids. For example if you were to eat spinach in its natural form to a liquefied form, the serum beta-carotene level would increase from 5.1% to 9.5%165.

  • This is why juicing can be of significant benefit freeing phytochemicals embedded in the food matrix. Boiling or steaming vegetables for too long can reduce the bioavailability of carotenoids by oxidizing them165. This is in contrast to lycopene in tomatoes a non-provitamin A carotenoid whose bioavailability is increased by heating165.

  • As mentioned above, consuming provitamin-A carotenoids in foods rich in monounsaturated and polyunsaturated fats will increase the bioavailability of these fat-soluble plant pigments.

Sources of vitamin-A in Western societies

  • In Western countries, about 50% of vitamin-A comes from animal sources and 50% from plant sources161.

  • According to the National Institutes of Health website, the Office of Dietary Supplements (ODS):

    “According to an analysis of data from the 2007–2008 National Health and Nutrition Examination Survey (NHANES), the average daily dietary vitamin A intake in Americans aged 2 years and older is 607 mcg RAE . Adult men have slightly higher intakes (649 mcg RAE) than adult women (580 mcg RAE). Although these intakes are lower than the RDAs for individual men and women, these intake levels are considered to be adequate for population groups.”

  • What is stated above as being adequate for 'population groups' could be vastly inadequate for subpopulations such as the young, uneducated, lower socioeconomic groups, the elderly and those with chronic illnesses or frequent infections of mucosal cavities (lungs, bladder, ears, bowels, sinuses).

Serum vitamin-A levels affected by infections such as measles

  • Vitamin-A levels in the blood can be severely decreased with infections as shown in children affected by measles.

    “It is now well known that measles can bring serum concentrations of vitamin A in well-nourished children to below those observed in non-infected malnourished children161

  • An article published in Lancet showed that there was a 50% reduction in maternal mortality by supplementing with beta-carotene or vitamin-A.

Vitamin-A and iron deficiency anaemia

  • Vitamin-A is needed to transport iron from stores to the red blood cell163 and as such it has been shown that iron deficiency anaemia responds far more favourably when vitamin-A and iron are given together. “A study of pregnant Indonesian women showed that 100% of the anaemic women were cured by combination therapy of vitamin A with iron, whereas only 40% were cured by vitamin A alone and only 60% by iron alone161.”

Low vitamin-A levels and thyroid function 

  • Low vitamin-A levels will also lead to poor thyroid function162. Animal studies have suggested that Vitamin-A affects the hepatic conversion of T4 to T3 (the active form of thyroid hormone)166

  • Low thyroid function in turn leads to impaired carotenoid metabolism and transport162 and there are often elevations in both retinol and beta-carotene blood levels called Carotenaemia leading to a yellowing of the skin.

  • A vicious cycle will occur if there is a suboptimal intake of vitamin-A as shown in the graphic opposite.

Cod liver oil - safe if used as directed

  • Some scaremongering is occurring with regard to the use of preformed vitamin-A suggesting it is safer to use carotenoids instead because of the 'braking' mechanism described above in the conversion of carotenoids to vitamin-A.

  • This is a dangerous message to give people as this could result in low vitamin-A levels and increased morbidity and mortality. It has been shown above how variable carotenoid bioavailability is depending on a multitude of factors and provitamin-A carotenoids should not be relied upon as the sole source of vitamin-A.

  • Most cod liver oil formulations will have safe levels of preformed vitamin-A provided the recommended dose is taken. Megadoses of cod liver oil can be detrimental to health, but this is unlikely if common sense is used.

  • A safe strategy would be to use a cod liver oil supplement or preformed Vitamin-A supplement every 2nd day and to then ensure highly bioavailable carotenoid intakes through the use of juicing of fruit and vegetables, or lightly cooking the vegetables  (steaming, boiling for short periods) and to also ensure an intake of fat with carotenoid consumption by haveing some olive oil, fish oil, avocadoes, oily fish with these high carotenoid foods. By consuming foods that are high in provitamin-A carotenoids, you will also be absorbing high levels of Vitamin-K another of the fat soluble vitamins. However, as stated, most cod liver oil supplementation if taken as directed, will have about 1/3 of the RDA of preformed Vitamin-A. So taking this on a daily basis will not result in toxicity. Choose one that has a standardized dose of Vitamin-A

  • Adults need around 3000 IU per day of Vitamin-A with a tolerable upper intake of 10,000 IULPI.

  • Vitamin A like vitamin D, is stored in the body and released as needed. Body stores may be severely depleted before any change in serum markers will appear. It is thus important to ensure adequate storage levels of these important vitamins.

  • It is important to note that blood levels of vitamin-A bear no correlation to the level of stored vitamin-A, in fact, liver stores will need to be severely depleted before there is a corresponding change in circulating vitamin-A levels169.

  • If the population as a whole has suboptimal intakes, then on an individual level, vast numbers will have very low levels of dietary vitamin-A being consumed leading to significant morbidity in terms of increased infections, asthma, otitis media, dry eyes, dry mouth, bladder disorders, cancers, thyroid dysfunction and poor general health. The likelihood that such ill-health will be attributed to suboptimal intakes of vitamin-A is very low indeed.

The important message:

  • Ensure you are taking enough Vitamin-D along with Cod Liver Oil or a standardized pre-formed Vitamin-A supplement.

  • Ensure you aer also getting enough Vitamin-E and Vitamin-K as well

  • This will ensure you are getting optimal amounts of all the fat soluble vitamins.

  • The studies showing adverse effects of previtamin-A supplementation would almost certainlhy have been in individuals who had significant deficiencies in the other fat soluble vitamins (see below)

The Vitamin-A & Vitamin D Antagonism Story

  • Northern European countries have the highest rates of osteoporosis167.

  • In many Northern European countries where vitamin D levels are low due to poor sunlight exposure and higher intakes of vitamin A, the antagonistic effects of these vitamins may cause a reduction of calcium absorption due to impaired vitamin D action167.

  • The oil soluble vitamins - A, D, E and K need to be taken in a balanced way. It is important to ensure that an individual is not suffering from vitamin D deficiency before administring vitamin A or to ensure adequate intakes of both vitamins when supplementing.

  • This effect should not drive anti-supplement sentiment but it does indicate that due diligence needs to be shown when using supplements in the same manner that a medical practitioner considers the pros and cons when providing a pharmaceutical as a therapeutic modality.

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