Vitamin A: Friend or Foe

It is well established that high retinoic acid (RA)  levels leads to teratogenic effects both in human and experimental models. Brain abnormalities such as microcephaly, impairment of hindbrain development, mandibular and midfacial underdevelopment, and cleft palate are all implicated.[1],[2]

Ingested vitamin A, a fat-soluble vitamin, is delivered to the blood via the lymph system in chylomicrons, and excess vitamin A is taken up by the liver as retinoic acid for catabolism by CYP enzymes.[3] Any remaining retinoic acid that is not catabolised is exported inside LDL particles, and it lingers much longer as retinyl esters in the vasculature in this form.[4] Excess retinoic acid is more readily stored in this way in LDL particles in the elderly. Vitamin A toxicity can lead to fatty liver and liver fibrosis[5] as well as hypertriglyceridemia.[6]

Concerns regarding potential toxicity from hypervitaminosis A have led to the recommendation that much, if not all, of the vitamin A requirement be met by consuming pro-vitamin A carotenoids, which have been thought to be readily converted to retinoic acid as needed.

Yet Dr. Georg Lietz of Newcastle University, the senior investigator in research published April 2009 in the FASEB Journal, reported that a high percentage of women in the UK are at risk of vitamin A deficiency. Two common genetic variants greatly lessen the body’s ability to convert beta-carotene into vitamin A.[7] He followed this up in 2012 with further clarification that a range of SNPs can influence the effectiveness of using plant-based provitamin A carotenoids to increase Vitamin A Status.[8]

Food Sources of Vitamin A

Only animal-derived foods contain retinol. Highest concentrations of retinol are found in liver (106µg/g), butter (6.84µg/g), hard and cream cheeses, e.g., Swiss cheese (2.5 µg/g), cheddar (2.8µg/g) and regular (not low fat) cream cheese (3.8µg/g). Eggs contain 1.9µg/g, and cow’s milk 0.6 µg/g.

Good sources of provitamin A include carrots (24.6 µg RAE [retinal activity equivalent]/g), sweet potatoes (16.4µg RAE/g), spinach (8.2µg RAE/g), kale (7.4 µg RAE/g), and broccoli (1.4µg RAE/g). Cantaloupe (1.69µg/g), mangos (.38 μg/g), and many other dark green or orange-yellow colored fruits and vegetables are also good sources of provitamin A. In the case of mangoes, however, up to 64% of the total β-carotene is present as the cis-isomer, which is not taken up or transported as efficiently as the trans-isomer.[9]

Aging is characterised by a peculiar chronic inflammatory status for which researchers have recently coined the term, “inflammaging,” a key aspect of which is the age-dependent expansion of effector T cells with pro-inflammatory cytokine production potential. Particularly in light of vitamin A’s emergence as a pivotal inducer of oral and self-tolerant immune function, vitamin A sufficiency should be recognised as a key contributing factor to longevity.

Research into the impact of vitamin A on immunology really took off when it was found that retinoic acid, a product of vitamin A metabolism, regulates the migration and differentiation of T cells in the intestine. Dendritic cells, which activate T cells and determine their activation and migration patterns, were found[10] to express the enzyme retinaldehyde dehydrogenase, which converts retinol (the form of vitamin A required for vision) into retinoic acid. Binding of this metabolite to the retinoic-acid receptor (RAR), expressed by T cells, results in enhanced expression of surface molecules that induce the T cells to migrate to the intestinal lamina propria — a layer of the body’s mucosal linings. Retinoic acid also promotes the generation of regulatory T cells[11], which control inflammatory immune responses, and of pro-inflammatory T cells in a diseased intestinal environment.[12]

Conclusion

Large individual variations in the actual absorption of β-carotene from foods and its conversion to retinol demonstrate that reliance on current data on retinol equivalents for vitamin A sufficiency is highly misleading and that a significant percentage of the North European population may be vitamin A insufficient, despite the fact that foods containing pre-formed vitamin A and β-carotene are generally available. Given recent discoveries regarding the importance of vitamin in balancing the activities of vitamin D and its pivotal role in promoting oral and self- tolerance, thus counterbalancing the tendency to “inflammaging,” vitamin A sufficiency should be considered a key factor in healthy aging.

References


[1] Sulik KK, Cook CS, Webster WS. Teratogens and craniofacial malformations: relationships to cell death. Development. 1988;103 Suppl:213-31. View Abstract

[2] Clotman F, van Maele-Fabry G, Chu-Wu L, Picard JJ. Structural and gene expression abnormalities induced by retinoic acid in the forebrain. Reprod Toxicol. 1998 Mar-Apr;12(2):169-76 View Abstract

[3] Russell RM. The vitamin A spectrum: from deficiency to toxicity. Am J Clin Nutr. 2000 Apr;71(4):878-84 View Abstract

[4] Krasinski SD, Cohn JS, Schaefer EJ, Russell RM. Postprandial plasma retinyl ester response is greater in older subjects compared with younger subjects. Evidence for delayed plasma clearance of intestinal lipoproteins. J Clin Invest. 1990 Mar;85(3):883-92. View Abstract

[5] Russell RM. The vitamin A spectrum: from deficiency to toxicity. Am J Clin Nutr. 2000 Apr;71(4):878-84. View Full Paper

[6] Ellis JK, Russell RM, Makrauer FL, Schaefer EJ. Increased risk for vitamin A toxicity in severe hypertriglyceridemia. Ann Intern Med. 1986 Dec;105(6):877-9. View Abstract

[7] Leung WC, Hessel S, Méplan C, Flint J, Oberhauser V, Tourniaire F, Hesketh JE, von Lintig J, Lietz G.. Two common single nucleotide polymorphisms in the gene encoding beta-carotene 15,15′-monoxygenase alter beta-carotene metabolism in female volunteers.. FASEB J. 2009 . Apr;23(4):1041-53.
View Abstract

[8] Lietz G, Oxley A, Leung W, Hesketh J. Single nucleotide polymorphisms upstream from the β-carotene 15,15′-monoxygenase gene influence provitamin A conversion efficiency in female volunteers. J Nutr. 2012 Jan;142(1):161S-5S. View Full Paper

[9] Ross C. “Vitamin A & Carotenoids,” in Modern Nutrition in Health & Disease,10 ed. Lippincott Williams & Wilkins: New York, 2006, p. 351-375

[10] Iwata M, Hirakiyama A, Eshima Y, Kagechika H, Kato C, Song SY. Retinoic acid imprints gut-homing specificity on T cells. Immunity. 2004 Oct;21(4):527-38. View Abstract

[11] Mucida D, Park Y, Kim G, Turovskaya O, Scott I, Kronenberg M, Cheroutre H. Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science. 2007 Jul 13;317(5835):256-60. View Full Paper

[12] DePaolo RW, Abadie V, Tang F, Fehlner-Peach H, Hall JA, Wang W, Marietta EV, Kasarda DD, Waldmann TA, Murray JA, Semrad C, Kupfer SS, Belkaid Y, Guandalini S, Jabri B. Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens. Nature. 2011 Mar 10;471(7337):220-4. View Abstract

Here Comes The Sun – How Vitamin D Relaxes Blood Vessels

It’s not just your mood that the dark months of winter can influence. Low levels of sunlight also mean lower levels of vitamin D in the body. Vitamin D deficiency can trigger a range of diseases but until recently little was known about the exact biological mechanisms behind this. A research team at the University of Veterinary Medicine, Vienna has now decrypted one of these unknown molecular mechanisms. Vitamin D regulates the elasticity of blood vessels and thus also affects blood pressure amplitude. The results were published earlier this year in the journal Molecular Endocrinology.[1]

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Older Population Experiences Vit D Deficiency More Commonly – What Are The Risks?

Having severe vitamin D deficiency may put people aged 65 years and older at more than twice the risk of having self-reported respiratory disease, according to an article published online May 6 in the Journal of the American Geriatrics Society.[1] The author Dr Hirani had in 2010 identified a similar pattern in older member of the UK population, and described it as a public health problem.[2]

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Vitamin D Testing – What About Reliability?

Following a series of questions raised by colleagues concerning the accuracy of vitamin D testing we asked Doctors Data, based in the USA to respond to some of the general concerns raised, as their lab has recently undertaken an extensive review of the methodologies utilised, to prepare for the next generation of vitamin D testing.

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High-Dose Vitamin D May Alleviate Menstrual Cramps: Study

Women who experience painful menstrual cramps could find relief from high-dose vitamin D3, according to new research – which suggests the dietary supplement could provide an alternative to painkilling drugs that are currently used.[1] Women with a history of severe menstrual cramps reported significantly less pain when they took an ultra-high dose of vitamin D five days before their next expected period.

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So How Much Vitamin D do I Need?

In practice life a number of questions arise relating to all supplemental suggestions and vitamin D is no different.

•          What do I need to be healthy?

•          How do I know what my levels are now?

•          How do I raise my levels if I need to?

•          What foods, supplements or lifestyle changes do I need to do?

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The Benefits Of Vitamin D On Gait, Muscle Strength And Balance In Older Adults

The usefulness of vitamin D is increasingly being explored and as a result better studies are being collated and brought into publication. A study published the Journal of the American Geriatric Society in Dec 2011 reveals that Vit D status is linked to physical functionality and represents a suitable replacement option. Whilst the dose recommended is modest, it is able to record an improvement, higher levels may provide greater benefit depending on base line levels.

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70% of Europeans suffer from low vitamin D levels

A group of experts has prepared a report on vitamin D supplementation for menopausal women after it was revealed that Europeans have suffered an alarming decrease in their levels of this vitamin. In their opinion, the ideal would be to maintain blood levels above 30 ng/ml. Vitamin D is essential to the immune system and processes such as calcium absorption.[1]

The team of experts analysed the conditions and diseases that are associated with vitamin D deficiency and recommended the intake of supplements in postmenopausal women. As well as stimulating calcium and phosphorus absorption, the vitamin D system has numerous functions. Low vitamin D levels are linked to rickets, osteomalacia, osteoporosis and the risk of bone fracture, cardiovascular disease, diabetes, cancer, infections and degenerative diseases.

“In healthy postmenopausal women, we have seen that a good level of vitamin D is linked to good physical fitness and has an effect on body fat mass as well as muscle strength and balance,” state the authors of the article published in the Maturitas journal.

The researcher explains that patients with risk factors associated with hypovitaminosis (obesity, pigmented skin, intestinal malabsorption syndromes and living in regions close to the North and South poles) should increase their intake to up to 4,000 IU per day. There is scientific evidence that a daily dose of 4,000 IU/day is not poisonous in healthy people.

Reference


[1] Faustino R. Pérez-López, Marc Brincat, C. Tamer Erel, Florence Tremollieres, Marco Gambacciani, Irene Lambrinoudaki, Mette H. Moen, Karin Schenck-Gustafsson, Svetlana Vujovic, Serge Rozenberg, Margaret Rees. “Vitamin D and postmenopausal health”. Maturitas, 71, 83-88, Jan 2012. View Full Paper

Cod Liver Oil vs TB

In a feature article in the Christmas 2011 edition of the well-known British Medical Journal, Professor Emeritus Malcolm Green revisited an 1848 study looking at the potential benefits of Cod Liver Oil in the treatment of Tuberculosis.[1]

In the study, carried out by physicians at the Hospital for Consumption, Chelsea (now the Royal Brompton Hospital), 542 patients with consumption (tuberculosis) received standard treatment with cod liver oil. These patients were compared with 535 ‘control’ patients who received standard treatment alone (without cod liver oil).[2]

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Mega Dose Vit D – Really?

Vitamin D supplementation, and what levels to use are common discussions amongst Nutritional Therapists. I have written a number of commentaries and reviews on this subject over the last couple of years and a recent paper published in the Journal: Joint Bone Spine presents a very interesting take on mega supplementation to restore Vit D status.[1]

Rather than looking at the results as a directive for vigorous upfront Vit D supplementation, as there are obvious considerations that make this as a universal approach very questionable, it remains clinically relevant, and may provide a degree of confidence. What is of greater interest is the rapidly declining levels of serum 25-hydroxy vitamin D (25OHD) after the first month and the differences noted in the weight of the patient.

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