The Physiological Role of Lutein in Vision and Disease

LIM JU BOO 

BSc Post Grad Dip Nutr MSc MD PhD FRSPH

Fellow

Royal Society of Medicine

London

Chemistry of Vision:

Rhodopsin or visual purple is a sensory protein-containing pigment found in the rod cells of the retina requiring retinol or vitamin A for its synthesis.

In the event of vitamin A or carotene  deficiency (carotene is a precursor of retinol or vitamin A), the synthesis of rhodopsin is compromised, resulting in night blindness, and in severe cases lead on to xeropthalmia and keratomalacia and total blindness.

Hence the importance of an adequate intake of vitamin A or fruits and vegetables containing carotene which can be converted into retinol (vitamin A) by the body

However, retinol is not the only nutrient that ensures good vision in the dark in particular.

Lutein and Carotenoids:

There are other carotenoids that are also involved in good vision in both in the day and at night , one of which is lutein, the other zeaxanthin.

Lutein is a one of the carotenoids that acts as an antioxidant responsible for protecting the eyes. This phytochemical is found abundantly in most brightly colored fruits and leafy vegetables and in plant-based foods that have deep orange or yellow colours.

Many colorful fruits and vegetables such as kale, spinach, broccoli, water cress, kangkong, sayur manis, including mangoes, water melons, citrus fruits, in fact in most tropical fruits, and even egg yolk are rich not just in carotenes, the precursor of retinol, but are also abundant  in lutein and zeaxanthin.

Green tea too contains lutein and zeaxanthin in good amounts besides the catechins, a subgroup of the flavonoids, as well as  vitamins C and E,


So does a Chinese herb called Gou Qi Zi (Wolfberries) which has very high levels of zeaxanthin, lutein, polysaccharides and polyphenols, all of them  have been shown to improve eyesight, prevent macular degeneration and diabetic retinopathy.

Their rich presence in most colorful fruits, vegetables, teas, berries and herbs protects the eyes from oxidative stress and vision loss.

Like retinol, lutein and zeaxanthin cannot be synthesized by the human body and hence they must be obtained by the consumption of plant-based foods rich in these sources. However, lutein may also be  giving by lutein supplements.

Although it is best to source lutein naturally through foods rich in them,  other antioxidants supplements or fortified foods may also be used to help increase levels of lutein, zeaxanthin and carotene levels in order to confer the full potential of lutein in terms of disease prevention, bioavailability, metabolism and dose-response relationships

When foods rich in lutein or lutein supplement is consumed, scientists and nutritionists believe this is easily transported throughout the body, especially to the parts of the eyes called the macula and the lens where it is wanted most. Nutritional and food scientists know that there are more than 600 different types of carotenoids found in nature, but only less than two dozen find their way into the eyes.

Of these, approximately 20, lutein and zeaxanthin are the only two left that are deposited in high quantities into the macular portion of the eyes.  The macula is the central area of the retina which is the light sensitive, and it is in this area that lines the inner portion  of the eye that  gives us the ability to see an optimal “20/20”vision  and visualize the full range of colours.

Oxidative Radical Damage:

Furthermore, the antioxidant properties of lutein to block off free radical damage caused by blue light from smart phones or from other sources have been reported in the journal Nature.

A diet lacking lutein and other carotenoids may increase the risk of developing age-related vision loss or disorders related to macular degeneration and cataracts formation

Nutritionists and medical researchers are aware that lutein protects healthy cells like rods and cones in the eyes and skin cells, and its ability to arrest the growth of malignant cells.

One of the most important parts of the eye is the lens. The function of the lens is to collect and focus light onto the retina. This is exactly why the lens has to remain clear and transparent for light to enter. It has to be free from the cloudiness which is indicative of the formation of cataracts.

Energy of Light:

The main reason why the lens becomes cloudy is due to oxidation of the lipids in the lens by ultraviolet light and blue light which are shortwave ends of the light in the electromagnetic spectrum.

The shorter the wave length or the higher the frequency, the greater the penetrating and destructive powers of the electromagnetic spectrum including light as given in the Max Planck equation:

E = hv

where,  E = energy delivered, h = Max Planck constant, and v = the frequency

Thus blue light and ultra violet of the Sun can energize molecules in the eyes, the skin  and other tissues liberating highly destructive free radicals to the cells, especially the DNA, initiation molecular lesions on the sites where the light or radiation is turned on.

However the presence of antioxidants like lutein and zeaxanthin is able to block off these highly distractive free radicals that may ultimately lead to vision impairment, both to the lens and to the retina.

Even for those who may, or may not have existing eye and vision problem other than short or long sightedness, including plenty of lutein in their diet or in supplements can prevent  vision impairmemt Thus it is important to ensure we have adequate lutein intake.

Preventative measures are the best ways to ensure that our vision and eyes remain  intact and healthy even till old age. It is thus strongly advised that both the young and the old should ensure adequate consumption of foods rich in lutein, or the use of supplements so as to minimize the risk of oxidative damage to the eyes.

Cancers and Heart Disease:

Even though lutein, zexanthin and other carotenoids are extremely crucial for vision and the eyes, their benefits is also extended to other areas of the body.


For instance, lutein is also used in the prevention of skin disorders, several types of cancer including colon or breast cancer, type 2 diabetes as well as minimizing risk factors associated with coronary heart disease.

Macular Degeneration:

Lutein may be considered a natural treatment for macular degeneration (AMD), which is probably the most common cause of blindness among older adults in countries where vitamin A intake is adequate but where lutein is deficient.  

Estimates show that more than 25 million people worldwide are affected by age-related macular degeneration or cataracts, especially people aged 55 and older living in areas where exposures to ultra violet rays of the sun is highest such as in snow covered mountains of Tibet or in the tropical sun like in Malaysia.

For instance, the incidence of AMD in the United States is predicted to triple by 2025 according to the American Optometric Association

Mechanism of Action:

Lutein protects the eyes by blocking off a portion of the short-wavelength UV light or blue light that have the most damaging effects on the most delicate parts of the eyes such as the retina and the macula.


Researchers at Harvard University have found that supplementing with 6 milligrams daily of lutein can lower the risk for macular degeneration by an average of 43 percent.

Cataract & other Studies:

Similarly, other studies have demonstrated that a higher dietary intake of lutein and zeaxanthin along with vitamin E is associated with a significantly decreased risk of cataract formation. While the research is still in its early stages, it is suggested that taking lutein three times weekly for up to two years may confer an improvement in vision in older people who already have cataracts or at risk.

Other benefits of lutein intake or its supplements include a reduction in  eye fatigue, glare and light sensitivity especially those who plays with their smart phones constantly especially in the dark. It assists the lens and retina to remain intact while strengthening the eye tissues.

Individual Variations:

However, the requirements of lutein like for all other nutrients differ from individual to individual.  No one person is biologically the same. It’s likely that even for those with a relatively high intake of antioxidant-rich foods, their blood levels might be correspondingly high in the various nutrients, and yet their levels in the tissues within their eyes and at retinal levels may still be too low.

Scientists have now devised ways of measuring macular pigment levels of lutein in the eyes to determine the risk for retinal disease. By determining the macular pigment optical density test (MPOD), nutritionists and specialist doctors can now formulate more precise dietary recommendations for lutein and other protective nutrient requirements based on individual responses, genetic predisposition and lifestyle requirements

Skin Cancers:

It was shown that carotenoids including lutein and zeaxanthin are not just present in the eyes, but also in the skin. It is postulated that lutein may be able to filter out high-energy wavelengths of visible light such as blue light and ultraviolet radiation by slowing down the rate of free radical damage and oxidative stress. A few animal studies have shown that lutein provide significant protection against light-induced skin damage, such as signs of aging, the loss of skin elasticity, and potentially skin cancer.

Lowers risk of diabetes:

It was also demonstrated in some animal studies that high levels of lutein and other carotenoids within the blood are associated with a better control of blood sugar. This may be translated to a lower risk of diabetes and its complications.


For instance, a 2000 study conducted on diabetic rats found that oral supplementation with lutein and omega-3 fatty acid or DHA was able to normalize all diabetes-induced biochemical lesions in the experimental group.

Compared to the control of rats not given lutein and DHA, diabetic rats taking the supplements showed   lower oxidative stress rates and less damage to the retina of the eyes, even though they were under hyperglycemic conditions.

Lowers Risk of Cancer:

There was some evidence that people who obtain more lutein in their diet have lower rates of breast, colon, cervical and lung cancers. However, we do not know exactly how lutein and cancer formation is linked currently, even though correlational studies have shown that adults with higher levels of lutein in the blood experience a reduction of developing several forms of common cancers.

Thus it may be possible lutein could offer as a part of a natural cancer treatment because of the fact that foods rich in lutein such as broccoli,  kale, spinach,  leafy green vegetables and all highly colored fruits  with high antioxidants scores  can  lower inflammatory diseases due to oxidative stress.

But more research is still needed to help us fully understand the role lutein and other carotenoids have on cancer, immune response, hormonal and cardiovascular functions, independent of other nutrients and phytochemicals that are found in fruits and vegetables.


One possibility is their epigenetic influence on how genes express themselves in the presence of lutein and carotenoid-rich foods.

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Cardiovascular Protection:

A few  observational studies have demonstrated  that xanthophyll carotenoids including lutein can reduce the risk of cardiovascular events and  coronary heart disease and stroke However as in previous studies that show potential cancer-protective effects of lutein, we are not quite  sure as yet at this moment in time how lutein could be cardiovascular protective?  

One such possibility is lutein anti-inflammatory and antioxidant properties may inhibit inflammatory response which currently scientists and cardiologists believe is the primary cause of heart and vascular diseases.  This hypothesis is currently replacing the out-of-fashion high cholesterol theory.

Studies conducted at the University of Southern California suggest that low levels of lutein within the blood might contribute to the thickening of artery walls. This elevates the risk for arteriosclerosis development and clogging of the carotid arteries that can result in cerebrovascular accident or stroke.

The USC’s observational studies show that populations with the highest levels of lutein in the blood experience less plaque formation in their arteries, as opposed to the other group with lower levels of blood lutein.   It was shown that the lesser lutein-rich plant foods they consumed, the more clogged their arteries. Perhaps more studies are needed to confirm this observation.

 

Another interesting observation is that after the researchers tested effects of lutein on human arteries that were surgically removed, there were fewer white cells present within the arteries after lutein supplementation was added compared to the controls. We know that the presence of white cells is suggestive of   an inflammatory response, and a subsequent blockage of the arteries which has no link to high or low blood cholesterol levels.

This may suggest the actions of free radical damage prior to atherosclerotic plaques and lesions.

The Contribution of Scientist in Medicine

The Contribution of Scientists in Medicine

I wrote an article in this blog "Are Doctors Clinicians or Technocrats?" just  hours ago. 

Here, in this small article, I thought I should continue my thoughts that medical scientists should not be left out with their hard earned scientific data for the advancement of medicine

What I wrote earlier,  of course does not mean clinical practice should only be confined by just looking at the history of the patient, by just looking at the signs and symptoms, do a  clinical examination.

All these methods  are very subjective depending entirely on the clinical acumen of the doctor but without any concrete objective measurements and without any data,  and then just prescribing the treatment.

This approach in modern medicine would be grossly wrong if medical technology can come to the  aid of the doctor with their advanced objective measurements and investigations.

Clinical Data Just as Important:

Clinical data can then be collected to look at the extent of the chemical and physiopathology, which would also be very valuable for follow-up treatment and monitoring

It would be utterly unacceptable if lab technology if available to confirm a diagnosis, but denied to the patient especially if they are cheap and  cost effective

Furthermore, there are many things in medicine we do not know, such as how do we defeat cancer yet not wanting to consult our scientists colleague who have the expertise in  molecular biology, genetics and epigenetics, who can study malignant cells express themselves, the behavior of their  genetic codes, codons and switches and their highly complex signaling pathways…etc., etc.

But to understand disease,  we need to call in our scientific counterparts working silently in research laboratories, and through their R & D develop rapid diagnostic procedures and drugs that may eventually give the tools to  clinicians to effectively manage cancer and many other unsolved and difficult diseases

Scientific Medicine:

But if we do not wish to use scientific methods but  confine our practice to just history taking, and physical examination, medicine will immediately come to a standstill for everybody –  for  the doctor, the patient and  worse of all,  the public.

Then there will be many, many diseases like autoimmune disorders like SLE, lupus, polycystic ovary syndrome, multiple sclerosis, cystic fibrosis, Crohn's disease, motor neuron disease, and even the entire range of reemerging  infectious and communicable diseases becoming  unresolved, if not growing bigger and bigger a threat

The Contribution of the Scientist

If the doctor does not wish to bring in the scientist as part of the health-care provider, but only himself as the stand alone contributor, then how is he going to treat the patient?

Where then can he get the medication because all the drugs including vaccines and diagnostics are the inventions of the scientist in his research into R & D. This includes the medical engineers who invented and developed all those different types of scans and imaging machines

It is the drug scientists who not just formulate and model the drug or the vaccine, but they were actually the ones who study their actions on body as well as its chemistry of the pathology.

They are also the ones who study their therapeutic action, their toxicities, work out the dosage, their interactions with other drugs or nutrients, their indications and contraindications, pharmacodynamics (mode of action), their pharmacokinetics (absorption, distribution, retention time, mode of excretion, etc.), and teach the doctor how to use the drug besides educating them on the precautions, etc. etc.

The doctor won’t know these because the drugs are not designed or invented by them. They are just the end-users together with the patient

Drugs like TV Sets

This is exactly like a consumer who buys a television set, a house computer, a smart phone, a microwave oven, a washing machine. All the consumer needs to know is how to use them by following the manual that comes together with the product. It is not their responsibility how the gadget works or manufactured, and even if told, he is hardly likely to understand either because pharmacology is not their field with just two months lectures about drugs during their medical training

All he is interested is how to use them by reading and following the manufacture’s pamphlets enclosed with the drug.

Hence if a doctor refuses to acknowledge most of the credits  to be given to his scientist colleague, then he will stand alone forever taking only  medical history,  looking for signs and symptoms, palpating and percussion the patient body, and auscultating the patient for heart murmurs, lungs for rales, rhonchi, stridor and pleural rubs, and elsewhere for bruits and bowel sounds. 

This he will do round and round in circles forever getting nowhere for him, or of any benefit to the patient

He has no choice if he wishes to use other methods to diagnose and treat the patient,  he must give due credit to the scientist who work brought to him all the lab diagnostics and scans available for him to proceed further,  much more than mere clinical examinations round and round, benefiting no one.

Treating the Disease, the Person or the Patient:

Unfortunately, the doctor does not study or research into disease. His role is merely to diagnose and prescribe the medication, but the medication is actually administered by the nurse. Sadly he treats the disease but not the patient as a person. He looks at everything from the medical point of view and forgets the patient is actually a person, and not a biochemical machine, but  with social and spiritual needs which must also be holistically treated, and not  just by  giving the medicine

The medical scientist on the other hand, only studies the disease, its chemistry and pathology, but does not treat the patient, let alone treat the patient as a person. He is only interested in research to give something new for the doctor to use, like a manufacturer producing a smart phone or a television set,  and sell it to a user  to use it  Both are grossly guilty of their short coming 

The Clinician- Scientist Partnership:

Thus clinicians, no matter how competent  they may be, must give way to scientific methods of investigation in order for medicine to advance. They just cannot confine their practice using just  clinical methods  without lab investigations. Then  they will get nowhere, and all of us in society will also suffer too because there is no way to diagnose a complicated case effectively, and no treatment can then be offered

Clinicians have no choice but to work hand-in-glove with medical scientists and researchers who actually are the frontiers of their scientific and medical knowledge. The scientists impact these knowledge to them through their publications in learned scientific and medical journals provided the doctors read them.

But all these scientific research in medicine and medical sciences must be able to be translated from bench into bedside through the middle party called translational medicine, and emerging field of medicine so that a medical graduate will turn into not just a clinician, but a clinician-scientists capable of handling complex scientific research.

At the moment it is the scientists, not the doctor who does  99.99 percent of the research work in medicine. However, neither the clinician nor the medical scientist can work separately, ignoring each other valuable work.  

Both are to be given equal tribute in the health care profession, because the doctor cannot work stand alone. Many other health care partners are also involved in a holistic approach to fight disease, pain and sufferings

The Nobel Prize in Medicine or in Physiology:

In fact all the prestigious Nobel Prizes in Medicine or in Physiology are awarded mainly to the scientists these days. They are actually the ones who work silently in their research laboratories except during clinical trials when both may emerge in public, else only the doctor and the patient are in view 

The Nobel Prize in Physiology or Medicine is widely considered to be the highest accolade in modern healthcare. Once a year, the Nobel Assembly at the Karolinska Institutet in Sweden announces a prize to recognize the significant medical contribution of up to three healthcare researchers.

The Royal Society of Medicine in London bemoans:

In a paper published by the Royal Society of Medicine in London, it was reported:

“We studied the overall trend in prizes and awardees to note that the proportion of clinicians receiving this award has been diminishing year on year. In the past 100 years of awards to medical scientists (excluding war periods where Nobel Prizes were not awarded to individuals); over 79% of Nobel Prizes in the first 30 years were awarded to clinicians. This contrasts significantly with the last 30 years, where only 26% of prizes have been awarded to clinicians”

  

(J R Soc Med. 2011 Sep; 104(9): 387–389).

Thus we can see the advancement of medicine has  now been taken over by medical researchers and medical scientists instead of by medical doctors and clinicians unlike 3 decades ago. The scientists  are deservingly  recognized as the actual frontiers  and contributors  of medical knowledge and medical advances  only possible by their hard work hiding behind the screens and  corridors of the health care profession

The Scientist Contribution:

In fact they contributed 99.99 percent of the advances in medicine by developing new diagnostics, new range of drugs, all the various scans and imaging techniques from X-rays to ultrasound, CT down to MRI and PET scans – all of them are developed by medical scientists and researchers,  and none by clinicians.

So did medical scientists find out causes of various diseases and how to prevent them? Very few of these studies came from medical doctors

The highest accolade in the form of Nobel Prizes in Medicine or in Physiology are praiseworthily given to the research scientists for their immense contribution to medicine

But if we were just to depend history taking and clinical medicine without any drugs formulated and designed by the pharmaceutical chemists, studied by the toxicologists, molecular biologists and evaluated by the pharmacologists, then absolutely no disease can be treated by the doctor. They will have nothing to offer?

The Long Dark Tunnel

The health-care industry is like a long dark tunnel

Hidden all along the sides of this tunnel are the unsung and unseen heroes, the medical researchers, scientists, inventors, and discoverers working silently towards the end of this tunnel just for two recipients to benefit their hard and unsung work

 At the end of this tunnel you will see a very bright light where you will see only two persons who are recipients  sitting in the open of a  bright glare. One is the doctor, the other the patient. The doctor gets the most limelight

But each year, the Nobel Prize Committee for Medicine or Physiology will call out just one or two most glaring contributors hidden somewhere at the side of this tunnel to come out to receive this world’s most prestigious Prize in Medicine to be in the real glare

There the tunnel is opened completely, not just at one spot at the end of this tunnel, but in broad daylight for the entire world to see the real hero

Ironically, more and more of these unsung heroes hidden in this dark tunnel are now being called out into the open to receive this most converted and glaring Prize and the doctor and his patient at end of the tunnel are asked to retreat into darkness and oblivion  

Obviously the medical community has to acknowledge and give way to the clinician’s scientific counterpart in order for them to progress for the benefit of the public. None can stand alone, as the scientific world is now multidisciplinary requiring expertise from various scientific disciplines    

lim ju boo BSc PG Dip Nutr MD PhD FRSPH

Fellow, Royal Society of Medicine

London                  

Are doctors clinicians or technocrats

Dear Prof Dr. Andrew

Thank you for agreeing with me.

A lot of diseases are Iatrogenic, caused by all these annual medical check-up, unnecessary investigations, unnecessary medications prescribed by the doctors themselves.

Let me give my frank view who makes a competent doctor.

By merely taking the medical history of a patient, and asking him a lot of questions, a competent doctor with very good clinical acumen would already be able to analyze and differential diagnose a patient’s illness without resorting to all those unnecessary and expensive lab tests, imaging and scans which to me all these images are just shadows on a film with no definitive diagnosis.  I only agree lab examinations provide some data of blood levels of a pathology which is not possible with just clinical examination

Thus,  I am not saying lab support is unnecessary. What I am trying to drive home to doctors is that these  blood, urine and serological-immunological tests  should be reserved for difficult cases where the clinical presentations  may mimic other conditions or disorders sharing the same signs and symptoms unless the signs and symptoms are presented as a group typical of the classical features (syndromes) of a specific disease.

In which case lab tests (biochemical, serological, haematological, microbiological, nutritional, molecular-biological assays…etc., etc.) may be necessary to confirm, or to monitor the progression of a disease or a treatment. These tests are just adjuncts to clinical examinations.

A physical examination is thus extremely important to diagnosis besides history taking. What about doctors who work in rural environment and among primitive societies where sophisticated lab technology and molecular-biological assays are completely not available? They will be sunk if they do not have the clinical skill

History taking and physical examinations are all non-invasive. They are cheap, reliable, and traditionally used since medicine was practiced by all cultures and civilizations long, long before all these sophisticated medical technology was invented by scientists in research laboratories to help the doctors.

History taking, listening carefully what a patient tells you (the patient is our mentor) and just some basic but relevant clinical examinations would already give a doctor with competent clinical acumen  almost 90 percent accuracy in his diagnosis without resorting to all those scans and elaborate lab investigations which are just  adjunct to support a diagnosis.

 I only respect a clinician who is a good diagnostician using  just his hands, ears, and eyes to assess (palpate, percuss and auscultate) without using all those unnecessary lab examination as “diagnostic clutches” This is my frank opinion on who makes a competent  clinician and a first class diagnostician

   

Just ask ourselves how did doctors diagnose well before all these sophisticated medical technology was developed by the scientists to help the doctors?  Yet these “ancient” doctors can make brilliant diagnosis, and also document and publish papers to describe the features, pathology, causes, outcome and prognosis of any disease s so accurately and so beautifully and have their description  published in standard textbooks of clinical medicine which even today modern doctors and medical students  read, learn and get their training

They  all learn from  these books written by doctors in the 18^th Century where all these lab tests and imaging technology were not available? They must be genus to describe, diagnose and treat disorders almost the same way doctors do today except they do not need lab tests 

The text books they wrote,  such as Sir Stanley Davidson textbook on The Principle and Practice of Medicine is not much different from the current Oxford or Price Textbooks on Medicine (just to quote two examples among hundreds of modern medical textbooks)

In fact the modern textbooks merely expand existing chapters of the older books without altering the  original  content. How did these “non-technological” doctors describe the pathology and diagnosis so many diseases  so accurately decades before all these lab tests, radiological and histology examinations became available? They must be genus, and we need to salute them.  Currently doctors need technological clutches to help them diagnose.  They “must” have all those lab data, without them they are sunk.  

 Ask ourselves this question that even today; despite impressive medical imaging and molecular medical tests, just history taking and physical examination remain indispensable in many contexts. Before the 19th century, the history and physical examination were nearly the only diagnostic tools the physician had, which explains why tactile skill and ingenious appreciation in the exam were so highly valued in the definition of what made for a good physician.

Even as late as 1890, the world had no radiography or fluoroscopy, only early and limited forms of electrophysiologic testing, and definitely no molecular biology to help doctors as we know it today.

Ever since this peak of the importance of the physical examination, reviewers have warned that clinical practice and medical education need to remain vigilant in appreciating the continuing need for physical examination and effectively teaching the skills to perform it; this call is ongoing, as the 21st-century literature shows.

To me, this is what makes a very competent, and an extremely skillful doctor who is an excellent diagnostician by using just his eyes, ears, hands and his brilliant analytical brain to differential diagnose even a mixture of complicated disorders. Can we do that?   

The rest who depends on lab and medical technological support are all brainless robots

This is my view Professor Dr.  Andrew.  I am sure you agree as an eminent medical-surgical specialist from prestigious John Hopkins School of Medicine

A Non Robot