Why We Age - Anti-aging and Life Extension

Definition of Retinol

Retinol is the dietary form of vitamin A and can be defined as a fat-soluble antioxidant.  It is important in both bone growth and also in vision.  We ingest vitamin A in two forms.  In plants such as carrots and spinach, vitamin A is absorbed in the form of compounds known as carotenoids (precursors of vitamin A known as Provitamin A).  From animals, we obtain vitamin A in the shape of retinoids (retinol, retinal and retinoic acid).  Vitamin A activity is always measured in relation to retinol.  Retinol can either be reversibly oxidized to retinal or irreversibly oxidized to retinoic acid.

The Molecular structure of Retinol

Definition of Carotene

Carotene is an orange photosynthetic pigment known as a terpene.  It is a dimer of vitamin A and can be found in several forms, including α and β-carotene.  These two forms of carotene are sometimes known as provitamin A carotenoids.  Excess carotene is stored in the liver and in subcutaneous fat and unlike retinol, it is non-toxic.  The α and β-carotene is converted to retinol when it is needed by the tissues of the body.  Note that this is done primarily by the tissues of the intestines and the lungs.

One thing to mention here is that of the approximately 600 carotenoids that have so far been identified in nature, 90% of them have been found not to be precursors of vitamin A.  Many of them have however been found to be powerful antioxidants.

Absorption and transportation of retinol
Retinoids are absorbed through the intestines and are then incorporated into structures known as chylomicrons (note that as vitamin A is a fat soluble vitamin, it must be ingested with fat for it to be absorbed correctly).  These chylomicrons first incorporate the retinoids in their ester form.  They then mediate the transportation of this form of vitamin A to the liver, where it is stored in the hepatocytes (liver cells) until it is required.  When the retinol is needed by the body, it is de-esterified and released in its alcohol form into the blood stream.  Retinol then binds to retinol binding protein (present in the blood stream) and is transported in this form to the target tissues.  Note that retinol binding protein synthesis is dependant on zinc.  Once this compound reaches the target cells a complex known as cellular retinoic acid binding protein then stores and transports the retinoic acid intracellularly.

General functions of Vitamin A in the body
Vitamin A (80% of which is found in the liver) plays a part in a number of processes in the human body.  Some effects of vitamin A are positive, but in some cases they can be negative (see below).  Note that the requirement for retinol in adult humans is between 500 and 1000 micrograms per day.

General Effects of vitamin A on the body

1. In the form of retinal, vitamin A plays an important role in vision.  In the retina of the eye, retinal is attached to opsin, resulting in the formation of rhodopsin.  Rhodopsin reacts with light, which then causes an amplifying chain of events, leading eventually to cGMP production and a signalling via the optic nerve.  Normal vision is therefore dependent on an adequate supply of vitamin A
2. In the cells themselves, vitamin A is important as a transcription factor.  Cellular binding proteins form a complex with vitamin A and then bind to DNA.  This triggers the transcription of important growth factors.  This mechanism is particularly important in epithelial cells, where this hormone-like process is the primary controller of cell differentiation, growth and shape 
3. Vitamin A has been found to offer some protection against chemical induced lipid peroxidation in the heart

Effects of reduced levels of vitamin A

1. Nyctalopia (night blindness) can occur if retinal is not made available to the eye for the formation of rhodopsin
2. Keratinization of epithelial cells resulting in a condition called follicular hyperkeratosis can result from vitamin A deficiency
3. Increased risk of infection
4. Impaired wound healing
5. Abnormal skeletal development in children
6. Vitamin A deficiency has also been observed to result in oxidative damage to the mitochondria in the livers of rats

Note that a deficiency in vitamin E may lead to a reduction of the availability of retinol as retinol then becomes more susceptible to oxidation.  A deficiency in either zinc, protein or iron can also result in the symptoms of retinol deficiency due to the negative affects on retinol plasma transportation and the release of retinol from the cells of the liver.

Effects of too much vitamin A

1. In severe cases of vitamin A toxicity, a patient may exhibit hydrocephalus (an increase in the amount of cerebrospinal fluid in the brain)
2. Vomiting
3. Tiredness
4. Constipation
5. Headaches
6. Hair loss
7. Brittle nails
8. Bone pain
9. Note that if a mother ingests too much vitamin A during pregnancy, then the foetus may develop abnormally

When provided as a supplement, the maximum safe level of retinol ingestion is 3, 000 micrograms per day.  Note that the consumption of high doses of carotinoids does not have the same toxic effects as the consumption of high doses of retinol.  This is due to the fact that the efficiency of carotinoid absorption decreases with increasing doses.  Also the rate of conversion into a more toxic form of vitamin A is too slow to contribute massively to overall vitamin A toxicity.

Anti-aging effects of Vitamin A

Vitamin A has been associated with many beneficial affects in the human body (as discussed previously). Most of the protective affects of vitamin A are however to do with the part that it plays in such processes as immunity, bone growth, reproduction and cell differentiation.  All very important functions.  Pro vitamin A substances such as the carotenoids have however been shown to have very potent anti-oxidant and possibly anti-aging affects.  

Beta carotene more specifically is a particularly potent anti-oxidant.  Just a single molecule of beta carotene can neutralise up to 1000 free radicals.  Beta carotene has also been shown through experimentation to offer some protection against such conditions as heart disease and cancer.  This is perhaps due to its free radical scavenging activities.  By mopping up free radicals, it could after all reduce the accumulative damage to cell membranes and DNA.  Although Beta carotene does also stimulate the immune system, which may also help to explain its general affects on health.

A number of population studies have shown that lower dietary levels of beta carotene can increase the risk of developing cancer later in life, particularly lung cancer!  Other cancers have also been associated (although evidence is less strong) with reduced levels of beta carotene.  These include breast, prostate, colorectal, ovarian and cervical cancers. 

One notable study was conducted by The Western Electric Company in the US.  This study monitored the dietary intake of a number of nutrients amongst approximately 1, 500 men through the 1950’s.  In this study, it was shown that the men who had higher intakes of beta carotene had correspondingly lower rates of cancer and cardiovascular disease.

One other study worthy of mention involves more than 120, 000 female US nurses.  This study has shown that woman who take in higher levels of beta carotene show a significantly lower risk of cardiovascular disease.

All in all Vitamin A has been shown to be very beneficial in the correct amounts and the Pro Vitamin caroteniods (particularly beta carotene) have been shown to be very conducive to a healthy life in a number of seperate studies. These substances may in fact help to retard the aging processes by a combination of mopping up free radicals and by bolstering up the immune system!

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Mark S D'Arcy