MEDICAL CONTROVERSIES: A CRITICAL READING

By: Nurul Hidayu Muhd Hatta, Nurul Aqilah Mazlan, Anis Amalina, Alif Firdaus, and Abdul

Muhaimin Hamzah

ABSTRACT

Due to the preponderous nature of the medical syllabus, students tend to memorize the

figures and facts as they are, without questioning why or how they come to be. This

leads to lack of capacity in analytical thinking that should be acquired during medical

school. Later, it gives rise to a problem once they are in position as doctors -due to the

dynamic field of medicine and its ongoing discoveries- which is the incapability to

distinguish between quality papers and those which are not. Hence, this working papers

is produced to enlighten the best approach in critical reading of medical literature. Upon

reaching this purpose, some examples of scholarly articles are mentioned to portray

general ideas of how critical reading should be conducted. This will be a stepping stone

to shift our paradigm, hoping that the future doctors would realize the importance of

such capability.

INTRODUCTION

Sources are considered primary, secondary, and tertiary based on the originality of the

information presented and their proximity or how close they are to the source of

information. In primary sources, researchers are actively participating in the research,

such as journals, thesis, conferences and reports. Interpretation of the original sources is

considered as secondary sources, which includes review journals, data compilations and

article indexes. Condensed and summarized information from primary and secondary

sources is being categorized as the third resources establishing encyclopedias, almanacs

and pocket books.

It is not uncommon for medical students nowadays to depend solely on tertiary sources

as the main references of medical knowledge. However convenient it is, they should be

woken up from such dogmatic slumber and trained to be literally proficient. We deem

this important seeing the reality of medicine as an inconclusive and ever-changing field.

Such ground breaking and rules changing discoveries as without doubt disseminated and

discussed within the primary sources. It follows that, depending to the tertiary sources

alone would render incompetence among future doctors.

Presenting three examples of controversial topics that had been debated for hundreds

of years (Helicobacter Pylori, Fluoride and Vitamin D) we come forward with some

principles in analyzing these scientific issues be it from primary, secondary or tertiary

sources. This is important for us as students to understand more details and not being

biased before we can conclude and state our stand for or against anything that had been

presented to us.

Going through the timeline history in every arising conflicts of scientific debates and

investigations, assumptions were made when some theories was brought forward

before conducting any studies, and criticizing upon the researcher's idea; all of this is

emphasized in our working paper.

METHODOLOGY

We have chosen three main topics to cover, primarily due to the controversies and

heated debates that surround them: the discovery of H. Pylori, the debate on Vitamin D,

and the fluoride and fluoridation of water. In discussing them, this paper adopts the

documentary analysis method. A timeline reference in accordance to the mainstream

narrative is established for each respectively. From there, important events and

significant milestone research papers related are enumerated which would later be

critically assessed and described so as to point out their strengths and weaknesses in

asserting their individual claims.

The aforementioned papers are searched and reviewed initially through the Jordan

University of Science and Technology (JUST) Library using a range of information sources

such as the OPAC system and Internet search engines. It is regretful that, despite the

hard work and effort trying to access them, the primary sources are not altogether

easily accessible if not unavailable. However, due to the nature of this study which

require digging back until the early 1900s where the Internet and digital documentation

was yet to be, it is considerable to our judgement that some data are of secondary type.

These would be noticed from time to time in the paper.

Although the main framework used in conducting this study is usually adopted by social

science research studies, this paper is essentially scientific. Hence, to preserve certain

standards by which scientific research papers are bounded, we have limited our analysis

and criticism as not to include political, economic nor social assumptions. It is not to

disparage these aspects, but rather, to remain purely in scientific realm. Nonetheless,

we are still students and our capability are limited to be highly data-centric. Instead, by

comparative reading, the contradicting research papers are analyzed side by side in

order to evaluate the consistency of methodology, aims, and research design. The

chronological development, framework flaw, and experimental biases are also stressed

wherever and whenever significant.

BACTERIA COCKTAIL IN SCIENCE GALA

Today, the nation has become the witness of the plot twist in the history timeline of; 1)

five hundred years discovery of peptic ulcer generally, and 2) one hundred years

discovery and rediscovery of H. Pylori particularly. It has brought a great astonishment

to the scientists with a significant change in the environment of our scientific

investigation in peptic ulcer. A miracle that hardly can be pictured that take us, as early

as the 16th century to dig upon the journey of the research in peptic ulcer. Specifically

the triangle conflict that sparks at the 19th century between A. Stone Freedberg, E.D.

Palmer and Barry Warren with Robin Marshall in order to prove that the main cause for

peptic ulcer is a bacteria that now named as H. Pylori.

In discussing the general outlook in research approach for any type of disease, it usually

starts with the research made to explain the characteristics of the particular disease,

then, the causes of the disease and finally it's treatement. However, when it comes to

the research on peptic ulcer, it is in the form of shattered pieces that the existence of

any connection from any findings are hardly being realised. This is the reason why the

most appropriate treatement of the peptic ulcer; an antibiotic for now, is discovered

one hundred years earlier before knowing it's real caused one hundred years later; H.

Pylori for now. It is believed that the inability to find the relationship between bacteria

and peptic ulcer leads to this outcome.

A Crooked Path Of Peptic Ulcer

To further discuss on this topic, it will be appropriate to first explain the timeline history

of peptic ulcer in detail.

It is divided according to; 1) up to early 19th century, 2) late 19th century, 3) during

20th century, and 4) early 21th century. However, this working paper will specifically

have it's focus in explaining further details for the timeframe of 20th century as it's the

crucial point in the history timeline of H.Pylori rediscovery which carries the main reason

of why this example is taken to be part of this working paper.

All of the researchers during up to early 19th century is focusing on describing the

alteration of gastric physiology due to the associated pathology that is found in that era.

This particular timeframe is divided into two phase; before and after the experimental

methodologies widespread1, as it exerts an effect upon the ability for the researchers to

carry out their research in more complex form of gastric disease.

Before the era of experimental methodologies widespread; Hippocrates, Avicenna and

M. Donati are among the standing figures that are recorded in developing ideas of

gastrointestinal pathology. Hippocrates is believed to be the first to describe gastric

symptoms which is an epigastric burning and aerophagia. Avicenna follows by

succesfully describing the relationship between pain, pyrosis and acute thirst with

gastric ulcer. In 1586, a case of gastric ulcer is being recorded for the first time by an

Italian physician, M. Donati.

Right after the experimental methodologies widespread, more new findings are being

found by the researchers. One of the four most significance is in 1728, G.E. Stahl has

proposed the usage of the word gastritis with a hypothesis that it is associated with

some episode of fever that could be related to superficial inflammation of gastric

mucosa, especially if the patient has the tendency to develop ulcers.

Then, in 1765 an Italian pathologist, G.B. Morgagni has described the erosions and

mucosal flattening as signs of gastric inflammation. In 1793, M. Baillie is believed to be

the first to make a clear description of the symptoms and morbid anatomy of gastric

ulcers. Finally, in 1842 a French pathologist named as J.Cruveilhier managed to

distinguish types of ulcers to be benign, chronic and cancerous.

During the late 19th century, there are many observations that supported the

1 Investigation perform via microscopical instrument

speculation regarding a causative role of an indescribable foreign bodies in gastric

pathology. It was unclear to many of the bacteriologists whether a specific organism was

the cause of a peptic ulcer or whether it was simply an abnormal accumulation of

organisms. Surprisingly, in 1868, although the main cause of peptic ulcer is not yet

known, A. Kussmaul suggests using bismuth compounds, an antibacterial agent, to treat

peptic ulcer. The antibacterial properties of bismuth were not known until much later,

but as the recurrence of ulcer was less after bismuth treatment, it has been used as the

component in the stomach therapy in Germany, Australia and Europe.

In 1875, a gastric bacteriologists, G. Bottcher together with his French collaborator M.

Letulle found bacterial colonies in the ulcer floor and in its mucosal margins. Those

bacteria according to him have a disease-causing potential that leads to ulcer. However,

in 1881, a pathologist called C. Klebs through his experiment reported that bacillus-like

organisms both free in the gastric area2. Then in 1889, W. Jaworski noted bacteria with a

characteristic of spiral appearance that he named as Vibrio Rugula. He suggested that it

might play a possible pathogenic role in gastric disease. However, P. Cohnheim later

makes a response upon Jaworski finding. He refers the organism as a “cell” that is just a

product of gastric mucus and acid chyme through the experiment he conducted. This

leads to the conclusion that the ulcers are caused by chemical factors not by bacteria.

In 1893, an Italian anatomist, G. Bizzozero through the specimen from the gastric

mucosa of 6 dogs noted the presence of spirochete organisms in the gastric glands and

parietal cells that later extended and affecting the surface of the pyloric and fundus

mucosa. In 1896, H. Salomon performed an experiment in transferring spirochetes he

found3 to the white mice. After a week, a colonization of the bacteria is found and

infected the gastric mucosa.

2 Lumen of gastric glands and between the cells of the glands and the tunica propria with corresponding

‘interglandular small round cell infiltration’.

3 In dogs, cats and rats but he did not identify it in human

Now, let’s diverge our focus to the most crucial and significance era in peptic ulcer

history timeline which is during the 20th century. From the previous hundred years

before entering this timeframe, there are less skeptical stands that hold by any

researchers in peptic ulcer investigation. However, due to A. Kussmaul method of

intubation of stomach and creation of experimental gastric pouch by I.P. Pavlov in 1869,

researchers are able to study the mechanism of acid secretion from the stomach. In

contrary, the inability for any bacteriologist to come out with a clear way in culturing

certain microorganisms lead to the precluded of experimental investigation in

confirming the validity of bacteria associating with peptic ulcer. In this particular era, the

conflict in proving the main cause of peptic ulcer was like a tug of war. However, things

to be clarified, most of the researches in the early 20th century believe that the

increasing in acid secretion is the main reason to cause peptic ulcer.

In 1905, F.Reigel claimed that hyperchlorhydria4 affected the development of chronic

ulcer. B. Moynihan later in 1907 suggested that acid was the cause of peptic ulcer. In

1910, Turck cultured B.Coli from feces taken in ulcer patients and injected into the

uninfected dogs. Later, he found the alteration in the gastric and duodenal mucosa that

according to him is an ulcer. However, in 1910, Gibelli claimed the inability to reproduce

Turck’s study. In addition to the same year, Scwartz has published the excess acid theory

affecting the ulcer with his well-known phrase of ‘no acid no ulcer’.

E.C. Rosenow later around 1913, isolated streptococcus bacteria from infected humans

with ulcer and injected the cultures into animal. Based on his observation, he concluded

three important things; 1) streptococci had a selective affinity to the gastric mucosa and

produced a local destruction of the glandular tissue, 2) Consequent upon such damage

caused autolytic capacity of gastric acid, 3) the reservoir of this bacteria were carious

teeth. However in 1915, antacids were being the first recommended in peptic ulcer

treatment. In the year 1917, as the respond towards E.C. Rosenow, a physiologist, L. R.

4 Refers to the state in the stomach where gastric acid levels are higher than the reference range.

Dragstedt performed an experiment and concluded that the bacteria actually migrated

from alimentary canal and infected the readily damage mucosa and leads to ulcer. He

did not believe that bacteria has substantial role in the etiology of the disease.

As have been mentioned before, this working paper will be focusing on the triangle

conflict between A. Stone Freedberg, E.D. Palmer and Barry Warren with Robin

Marshall. This is the particular point in the history timeline of peptic ulcer that the

conflict begins and further criticisms and explanations will be based on this particular

part. In 1941, Freedberg with the help from Barron investigated the presence of

spirochetes in the gastric tissue from patients who had undergone partial resection

surgery. They are the first researchers recorded to use a silver stain method of DaFano

that later are used by Marshall and Warren to prove their study.

Although they are believed to have implemented the right method, it was still not easy

to identify the organisms. However, they finally managed to come out with a conclusion

that the spirochetes were more frequently presented in ulcerating stomach compared

to nonulcerated stomach (53%, 14%). Unfortunately, Freedberg findings are being

challenged by researchers in many sides including E.D. Palmer.

In 1954, Palmer obtained gastric mucosal biopsies from 1180 subjects using a vacuum

tube technique. He then used standard histological technique to check for the existence

of any spirochetes. There were no spirochetes in any of the specimens he examined. He

then concluded that the results of all previous researchers could be best explained as a

postmortem colonization of the gastric mucosa due to the effect from the oral cavity

organisms. He also postulated that spirochetes were normally occurring commensals of

the mouth. Palmer’s work thus brings a great obstacle for any researchers who are in

favour in proving the connection between bacteria and peptic ulcer. In 1979 the plot

twist in the peptic ulcer research world starts when Warren observes H. pylori in a

gastric biopsy.

Later in 1981, Marshall joined Warren and they successfully treat their first peptic ulcer

patient with antibiotics. In 1982, Marshall and Warren begin their first study to

determine the relationship between H. pylori and peptic ulcer as they make their first

successful culturing of H. pylori. Marshall later presented his and Warren's results at a

local College of Physicians meeting but he met with criticism due to the believed at that

particular time of acid as the cause of peptic ulcer. In 1983, after many attempts in

trying to publish their findings, The Lancet at last accepted their research paper. To

further proved their research, Marshall intentionally consumed H. pylori and took

antibiotics and the symptoms he experienced was relieved and finally in 1984 Marshall

published the results of his self-induced infection and his findings are being accepted.

Lastly, in the early 21th century until now, more researchers started to put more

interest in studying H.Pylori. In 2005, B. Warren and R. Marshall are awarded the Nobel

Prize in Medicine for their work on H. pylori and PUD. Therefore, the conservative

believes regarding increasing in acid secretion as the main cause of peptic ulcer, remain

silence.

CRITICAL REMARKS

The whole discussion previously is the outline in the path discoveries of the

etiopathologies of peptic ulcer. However in this section, this working paper will be

commenting on the assumptions that being raised by the researchers. In conjunction to

this, certain criticisms are established to initiate critical thinking upon reading their

published scientific papers. This section is further divided into; 1) assumptions and

criticisms in the history development of H.Pylori in peptic ulcer, 2) assumptions and

criticisms in the research papers produced by A. Stone Freedberg, E.D. Palmer and Barry

Warren with Robin Marshall.

In looking upon the history development of peptic ulcer which is the first part of

discussion in this subtopic, a few questions that play a significant role are; 1) why the

dogma of bacteria as the main cause of peptic ulcer is being rejected by many

researchers until in the early of 20th century, 2) why the doctrine of excess acid secretion

as the main cause of peptic ulcer is well received by majority since 16th century? Is there

any difference in the methods used to prove their ideas of etiopathologies in peptic

ulcer or maybe is it because of the unwillingness for any reformation of thoughts?

After a careful reading made in both the development history of H.Pylori and excess acid

secretion, the path that pictured their journey is believed to be different. There are

many bacteriologists that come forward in proving the idea of bacteria infecting the

mucosal layer of stomach that later leads to ulcer. There are also many physiologist and

pathologist that able to connect the excess gastric acid with ulcer. From all the previous

research papers, most of the bacteriologist keep on looking at the component that

present near the ulcer. They then prove that there is an existing of bacteria and assumes

that maybe the bacteria caused the ulcer.

However, the most significant failure that done by the bacteriologist are; 1) the inability

to show the mechanism of action done by the bacteria to cause ulcer, 2) the anatomical

physiology of the bacteria in producing ulcer. This is believed as the reasons of why their

ideas are not being supported. In comparison to the excess acid theory, the ability of the

researchers to explain the mechanism of low PH of the liquid present in stomach, and

the connection between the effects of low PH to the mucosal layer of stomach, make it

obvious that the idea is more concrete.

However, this stand of excess acid is really convincing until later, H. Davenport and C.

Code in 1955 through their observations suggested that mucosal injury actually occurs

regularly, but does not lead to clinical disruption due to the present of gastric mucosal

barrier coating it that consists of several protective components. So, this somehow

proves that the excess acid secretion would not easily cause ulcer due to presence of

this protective layer. But, as researchers still unable to prove the etiology from bacteria,

the notion on the main etiology of peptic ulcer remains in vain.

Next, lets move to the second aspect of our discussion in this section.

The scientific investigation world is shocked by the revolution findings made by a few

researchers started in the early 20th century that challenged the conservative thought of

peptic ulcer etiology; excess acid secretion with a definite proof. This early steps has

shaken the ignorance of many researchers who are not ready for the reformation in

peptic ulcer approach as a whole. This is why, as mentioned earlier this working paper

will put a great focus on this particular timeframe, however, without neglecting the

importance of others.

It is very crucial to look upon the researchers who play great roles in this era. Among the

most significant researchers that create a triangle conflict in this revolution of proving

H.Pylori as the main cause of peptic ulcer are; 1) A. Stone Freedberg, 2) E.D. Palmer and

3) Barry Warren with Robin Marshall. Therefore, this working paper will be describing

the assumptions made by all of the mentioned figures and establish critics that are

believed to be valid upon them.

A.S. Freedberg is a person that starts this thought twist by publishing his research paper

“The Presence Of Spirochetes In Gastric Mucosa” in 1940. This research paper is

believed has best describe the characteristics of H. Pylori that is still ‘not known who’ at

that era. The difference that carried by A.S. Freedberg compared with other

bacteriologist before him are; 1) he is trying to prove whether these organisms are

natural inhabitants of human gastric mucosa or are just post-mortem or agonal

saprophytic invaders, 2) he is using the silver impregnation method of DaFano which is

the only way in the early 20th century that is believed to make the H.pylori visible.

Among the important conclusion he made through his experiment using gastric tissue

from 35 patients who were subjected for gastric resection5 are; 1) spirochetes are

rarely found in the mucosa of gastric tissue resected for duodenal ulcer, 2) spirochetes

are frequently found in those stomachs whose mucosa is ulcerated, and 3) the silver

impregnation method of DaFano will demonstrate spirochetes in the gastric tissue of

human.

5 19 patients with stomach carcinoma, 14 patients with duodenal ulcer and 2 patients with gastric ulcer.

According to the result of his experiment, he managed to prove that the bacteria are not

a natural inhabitant of gastric mucosa. However, a few crucial things that leads to his

failure in his research are; 1) the inability to prove through his specimens whether this

organisms did or not hold a pathogenic significance. He was left in astray just like the

previous researchers who were also unable to prove this relation, 2) the inability to

grow the bacteria collected from the gastric tissue resection. As he was only able to see

the bacteria by silver staining, it is difficult for him to make further investigation as he

will need more and more patients, and 3) the inability for him to convince his superiors

and colleagues upon his findings. The effect of the failure in growing the bacteria caused

him to be unable to confirm his findings. As it is an unproven paradigm of believing

bacteria as the etiology of peptic ulcer, he is being discourage by everybody and was

accused that his work was wrong. At last he abandoned his research and later he come

out with a great confession:

The longstanding attitude in the department was "if you find it

difficult to pursue a problem, drop it and switch to something

you could learn something from, because there is so much

unknown in our area and medicine."

Next, the second figure that among the individual that exert more pressure on the

finding done by A.S. Freedberg. In 1954, E.D. Palmar has made an unpredictable twist by

crashing the idea of bacteria as the etiology of peptic ulcer. Due to his prove from his

experimental investigation, he has set back the research on bacteria for more than 30

years with a famous phrase that ‘no bacteria can live in the acidic environment of

stomach’.

Palmer performed a research with 1180 gastric biopsies that he later makes a

histological investigation. Through this technique he is unable to find any single

spirochetes in the gastric biopsies. He finding is well accepted due to a few reasons, 1)

he make a research by using a huge sample that leads to a better specificity in the result

outcomes, and 2) he hold a consistency in his result by the absent of spirochetes in all

the biopsies he used. These two reasons put a great foundation on his argument.

However, there are few fallacies that he made along his experimental investigation

which we should put our focus on; 1) the reason that is believed behind his absolute

negative result is due to the histological method he used to view the bacteria. As proven

from the previous researchers that silver staining is the best method in viewing the

H.Pylori. The failure of him in using this silver staining technique could questioned the

aspects of sensitivity and the accuracy of his findings, and 2) he does not mention in

detail regarding the gastric condition of the patient he took gastric biopsies from. Are

they affected with any gastric pathology such as ulcers or carcinoma? As it has a crucial

affect in the presence of H.Pylori. Patients that are free from gastric pathology usually

but not all do not have H.Pylori existence in their stomach mucosal. Patients that are

affected by ulcers, especially stomach ulcers usually do have H.Pylori existence in their

stomach mucosal. Therefore, it could be because his patients were from the group of

individual that free from any gastric pathology, so it was possible for him to come out

with such negative result.

Finally, the two figures standing in this triangle conflict of H.Pylori research are B.

Marshall and R. Warren. After many trial of trying to publish their finding finally The

Lancet accepted their paper on “Unidentified Curved Baciili On Gastric Epithilium In

Active Chronic Disease” in 1983.

Based on 135 gastric biopsies specimen, they managed to detect H.Pylori using silver

staining method. A few significant findings that should be highlighted are; 1) they

connected bacteria (curved bacilli) with gastritis instead of directly referring bacteria

leads to ulcer. The mechanism of action in H.Pylori is by inducing inflammation, then

later leads to ulcer. By approaching the intermediate factor which is inflammation to

connect the relationship of bacteria with ulcer, it takes them one step forward in

proving the etiology of peptic ulcer, 2) They managed to explain the mechanism of

action done by the curved bacilli; H.Pylori. Through their observations, they noted that

the infiltrated area of bacteria cause reduction in mucus layer of stomach. This causes

the mucosal layer to be in direct contact with the acidic environment of the stomach

and corrodes the layer, 3) they differentiated the anatomical position of other bacteria

found in the stomach with H.Pylori. This proves is very crucial because there are a lot of

bacteria commensals in the stomach and they are proven to not cause harm. Therefore,

it’s very important to distinguish one from the other.

Through the research made by them, A.S. Freedberg finding 50 years ago starts to make

sense in two aspects; 1) Marshall and Warren managed to detect H.Pylori through the

same method used by Freedberg. Therefore, the possibility that the organism that

freedberg saw was H.Pylori, 2) they used Freedberg research paper as one of their

literature reviews in proving the etiology of bacteria as pathogen.

However, their research paper was not totally acceptable, not particularly because of

skepticism but it is believed because of certain prove that seems lacking which are; 1)

They are unable to prove how does the curved bacilli, H.Pylori survive in the acidic

environment of the stomach as the other bacteria that reside in the stomach does not

located near the acidic environment. This condition is worsening due to the claimed

made by Palmer previously that no bacteria can lives in the acidic environment of the

stomach. As Marshall and Warren themselves are unable to prove the statement of

Palmer was either wrong or right, therefore they are stricken by many criticisms, 2) The

pathogenicity of this bacteria is unproven through their experiment. They failed to

explain the identification and clinical significance of how this bacteria causing the peptic

ulcer. The only thing that they can prove is how it was connected with inflammation of

the stomach. As the main concern of that particular era is to find the etiology of the

peptic ulcer, their findings are not sufficient enough to convince other researchers.

However in 1984, as Marshall realized the only way to prove his findings is by showing

how the bacteria leads to peptic ulcer, he decided to make himself as the subject of

experiment. By confirming that he has not being affected by the H.Pylori through

endoscopy and gastric biopsy, he later consumes the H.Pylori and starts to look for any

changes. Surprisingly, he was being infected and puss like-cells were later found in his

gastric mucosal. This experiment eventually proves that the bacteria are related to the

cause of ulcer and he’s proposal is being accepted world widely.

To conclude, H.Pylori discovery is being used as one of the examples in this working

paper due to its significant curved path and journey that filled with a lot of debate and

conflict. It demands critical understanding in the approach of new ideas that teach a

person to analyze things instead of trusting everything.

FLUORIDE: TWO SIDES OF THE SAME COIN

A steady bombardment of scientific assays upon fluoride issue is one of the most

remarkable episodes in the history of medical controversies. Fluoride as a natural

elements embodied in rocks and soils is acknowledged to have good archives in the

dental health studies. However, many ongoing debates have given illusion to scientific

uncertainty portraying that the growing consensus of fluoride’s contribution to health

has now doubted.

Dated back in 1900s, American dentist Dr Frederick Mckay marked the start of fluoride

research and are shedding wonder on the oral health regimen measure, revealing an

astonishing connection between consumption of fluoride and resistance of teeth to

caries lesion. The discovery was in Colorado Spring,Colorado when he witnessed many

local residents exhibited brown stains on their permanent teeth; fluorosis phenomenon.

Dr Mc Kay with the help from Dr G.V Black, Dean of the Northwestern University Dental

School in Chicago in 1920 suspected that something either in or missing from the

drinking water causing the mottled teeth. Extensive research on that matter made

another significant authentication that these stained teeth were surprisingly resistant to

decay or caries. Since then, fluoride’s ability to benefit the initiation and progression of

dental caries are well documented from discrete sources.

Dental caries is an infectious disease in which bacterial byproducts such as acids dissolve

the hard surface of teeth; enamel. Left undisturbed, the bacteria would penetrate the

enamel attacking underlying tissues result in loss of teeth structure, pain and would

thereon progress to complications.

Fluoride works to caries-preventive effects through mechanism in which it abated the

corrosion of enamel and enhancing the building up process. The concentrated fluoride

in saliva are then taken up along with supporting calcium elements to establish an

improved acid resistant enamel crystal structure.

Fluorine is one of the most reactive of all chemical elements. It is not therefore

encountered in its free state naturally; only in combination with other elements as a

fluoride compounds. Fluorite (CaF2) is a common fluoride mineral of low solubility

occurring in both volcanic and sedimentary rocks. Thence, CaF2 found most abundant in

groundwater supply. Nearly every source of food and water contains at least a small

amount of fluoride. Seawater contains an average of 1.1 mg/L of fluoride and human

fresh water reserves contain an average of 0.01-0.3 parts per million. Thereupon,

implementation of fluoride in water supply has been endorsed by most of the public

health authorities.

US Centers for Disease Control hails water fluoridation as one of the top ten public

health achievements in 20th century.It is estimated that over 300 million people in 39

countries worldwide live in areas where water supplies are fluoridated. Some countries

went on installment but later on get it cut off in Netherland, Sweeden, East Germany,

Finland and more. There are also countries that never enforced water fluoridation in

Austria, Belgium, France, Norway, Italy as they prefer different fluoride mode; salt,

toothpaste etc. From American Dental Association(ADA), community water fluoridation

is only an adjustment of the naturally occurring fluoride levels in drinking water to an

ideal level recommended by the US Public Health Service; 0.7 – 1.2 parts per

million(ppm) with variation depending upon climate.

Standards regarding optimal levels of fluoride in the water supply are developed on the

basis of epidemiological data collected more than fifty years ago. The favorable level of

1 ppm was chosen, largely on an arbitrary basis to achieve the maximum reduction in

dental caries and the minimum prevalence of fluorosis. Attempts worldwide to

introduce water fluoridation are often thwarted. Nonetheless, this major public health

initiative continues to meet considerable opposition whenever it is mooted; by further

scientific works being done. This proponents and opponents ever evolving altercations

would require fair resolution to be advocated upon which of which are scientifically

coherence. Furthermore, this analyzing information from both parties would aid in favor

to pro, neutral or anti fluoride perspectives.

Fixed Variable of the Research

Public health authorities, ensure to fluoride safety on children teeth had no misgivings

about carrying out this very unusual experiment without interest about how fluoride

could affect adults. This refers to study in 1945, sodium fluoride products from industry

Alcoa Aluminium Company was added to Newburgh NY’s water supply at about 1mg/L

of water. Kingston NY as the control city for comparison purpose was left fluoride-free.

The Newburgh/Kingston study was declared a ‘success’ after 3 years observation. The

findings indicate that there is an inverse relationship between the prevalence of

dental caries and fluoride if the fluoride is taken during the years of tooth development.

Approximately 3,400 children are included in the Newburgh data and 2,800 children are

represented in the Kingston data. Adults were never tested and how would this

experiment be claimed to cover margin of safety of the wide range of individual

suspected in a large population?

The issue here is the way research experiment was being conducted concerning

relatively easy factors to be taken into consideration; age and concentration degree

intake for certain people liably prone to fluoride toxicity.The permitted water

fluoridation that to be ingested for the whole population has unheedingly exclude the

effects on adults and the affair of vulnerability of individuals to over-consumption of

fluoride. This certainly be applicable to people especially soldiers, are exposed to

substances and conditions that will interact with fluoride exposure and magnify harmful

effects; exposure to beryllium, lead, strontium, aluminum.The people with chronic

diseases; Diabetes Mellitus, kidney impaired patients that they tend to consume more

water as to nature of compensating the disease pathological essence are as well be

included. Does this study could be a safety principle index of scientifically tested

fluoride-safe population entirely?

Human-Animal Dose Correlativity

A basic dogma in medicine is that effects of substances on human body depends on the

dose to which the body is exposed. A little may be beneficial; a lot of the same can be

harmful. From 1995 paper research by Phyllis Mullenix, ‘Neurotoxicity of Sodium

Fluoride in Rats’, it is reported that brain function was speculative to fluoride, that the

effects on rats behavior depended on the age at exposure and that fluoride

accumulated in brain tissues. Rats exposed as adults displayed behavior-specific changes

typical of cognitive deficits, whereas rats exposed prenatally had dispersed behaviors

typical of hyperactivity. Criticisms of the study say that the results in rats are not

relevant to humans because the doses used were too high (75-125 ppm sodium fluoride

in drinking water). These criticisms are without merit because doses in rats produce a

level of fluoride in the plasma equivalent to that found in humans drinking fluoride in

water. The conviction that animals study were doubted in relevance to human most

matching presentation was a perversion of the scientific method as well as a major

betrayal of the most basic professional principles of public health; testing on animals

prior to humans.

However, proponents of fluoride standed up with firm evidences that the fluoride tested

in animal studies is of different type of fluoride used in the community water supply. A

pharmaceutical grade of sodium fluoride is most of the time being used in animal

studies whereas industrial grade sodium hydrofluorosilicic acid is installed in the water

supply. A crude assumption was made that once sodium hydrofluorosilicic acid is diluted

within water and the solution brought to a neutral PH, it would be equivalent in all

respects to a solution of sodium fluoride;the one use in animal studies.

Efficacy of Fluoride

When water fluoridation first began in the 1940s, dentists believed that fluoride’s main

benefit to teeth came from being swallowed during the tooth-forming years. This belief

that fluoride’s primary benefit was ‘systemic’ and ‘pre-eruptive’. A systemic benefit is

one that comes from ingesting fluoride, and a pre-eruptive benefit is one that occurs by

swallowing fluoride before the teeth erupt into the mouth. The premise underlying this

belief was that, since ingesting fluoride increased the fluoride content of the teeth, the

teeth would be more resistant to decay for life.

Now,epidemiological data from recent community water fluoridation studies supported

the current view that the caries effect of fluoride is almost exclusively ‘post-eruptive’

and the mechanism of action is ‘topical’. That’s why there are numerous dental products

being invented including toothpastes, mouth rinses, fluoride gels, fluoride varnishes,

and fluoride supplements.

These large and evolving studies of credible evidence-based investigations have been

proven that indeed the apprehension of fluoride should not be renounced after all.

Abide with all discussions and controversies to be put up with, the image of fluoride as a

medicinal substance rather than toxic contaminant has at most been verified.

Propagating the idea of how fluoride is useful and should not be abolished, advanced

scientific enquiries would one day be gaining culminated approve in a new perception of

fluoride studies.

Natural and Artificial Fluoride Resemblance Effect on Brain.

A study published in the International Journal of Environmental Studies, and led by

Roger Masters, Emeritus professor of government at Dartmouth, describes a factor that

is correlated with higher lead levels in children. Analyzing a survey of over 280,000

Massachusetts children, the investigators found that silicofluorides; artificial chemicals

widely used in treating public water supplies are associated with an increase in

children's absorption of lead. Exposure to lead is now well recognized to be an

important cause of mental impairment. In their analysis, the investigators found that

levels of lead in children's blood was significantly higher in Massachusetts communities

using the silicofluorides than in towns where water is treated with sodium fluoride or

not fluoridated at all.

However,a study conducted in China found no difference in the low blood lead

concentrations of the children in high-fluoride, lower IQ Wamiao and low-fluoride,

higher IQ Xinhuai experiment. These results thus make it very unlikely that the

differences in IQ of the children living in Wamiao and Xinhuai are the result of

differences in exposure to lead rather than to fluoride.

The highlight of these two different experiments result is that of the anticipated action

natural and artificial fluoride could possess. Silicofluorides are largely untested said

Professor Roger Masters, who pointed out that nearly all of fluoridated drinking water

supplies are treated with silicofluorides. Virtually all research on fluoridation safety has

focused on sodium fluoride,the natural fluoride available in ground water while

silicofluorides are artificial chemicals introduced in most of community water

fluoridation.

This aspect being brought up to the issue of resemblance in effects of expected result

from natural and artificial fluoride compounds. On the other hand, the brain study

support neither the possibility of adverse effects of fluoride exposures on children’s

neurodevelopment nor not having any correlations. But if digging more on reasoning

and factors to abundant study of fluoride-brain issue would help to constitute ideally

unbiased evaluations. Future research should formally evaluate dose–response relations

based on individual-level measures of exposure over time, including more precise

prenatal exposure assessment and more extensive standardized measures of

neurobehavioral performance, in addition to improving assessment and control of

potential confounders.

Fluoride on Osteoporosis

Water fluoridation has been widely proposed for its dental health benefits, but concerns

have been raised about the balance of skeletal risks and benefits of this measure.

Sodium fluoride treatment for osteoporosis was first introduced by Rich and Ensinck in

1961. They based their treatment on epidemiologic studies showing increased skeletal

radiodensity in persons exposed to high natural fluoride levels. Other investigators

proceeded to study the effects of fluoride on osteoporosis and in 1972, Jowsey et al.

recommended combined use of sodium fluoride, vitamin D, and calcium. The objective

of fluoride therapy in osteoporosis is the restoration of a normal bone mass. The main

effects are suspected to be increased bone formation due to stimulation of osteoblastic

activity and decreased bone resorption brought about by the affinity of fluoride for

becoming incorporated into the bone minerals as fluorapatite, which appears to be less

susceptible to resorption.

There are two prospective double-blind studies recently reported from the USA: one

from the Mayo Clinic and the other from the Henry Ford hospital investigating on

vertebral fractures susceptibility on postmenopousal women. Despite recent reports

concentrating on the problems associated with high-dose fluoride regimens,therapy for

established vertebral fracture syndrome in both hospitals has been shown to be of value

and associated with an increase in bone density and a reduced incidence of vertebral

fracture.

Fluoride therapy, however, remains the only known anabolic treatment for osteoporosis

apart from anabolic steroids with their well-documented side effects of liver toxicity.

Albeit concern about a possible increased incidence of hip fracture in patients on

high-dose treatment, this form of therapy should not be abandoned.

Evidence relating water fluoridation to hip fracture is based upon pharmacological

assessment and therefore several studies suggest the data on the relationship

between water fluoride intake and hip fracture risk at the individual level, and data

relating fluoridation to bone mineral density are required. Until these become available,

the burden of evidence suggesting that water fluoridation might be a risk factor for hip

fracture is weak and not sufficient to end the progress of the water fluoridation

programme.

In conclusion to community water fluoridation practice,as the arguments of both parties

proponents and opponents of fluoridation are continuously rejustified by scientific

hypothesis, the readers should account two-sided presentation of information as to

avert any biased media reporting. On the one hand, the qualitative researchers need to

remain close and intimate to their collected narrative. However, hierarchies of evidence

and trustworthiness criteria and all demand that the researchers maintaining distant

and balanced on the collected data. Personally, I think that both count. It is a must to

implement measures such as cross-checking, counter-checking, using qualitative

software (whenever it is appropriate)in order to deter doubts. This would eventually

help qualitative researchers remain objective and unbiased when providing her/his

interpretation of results.

THE SAGA OF VITAMIN D FROM MISNOMER TO CANCER

The major circulating form of Vitamin D is 25-hydroxyvitamin D, often abbreviated as

25(OH)D. Nevertheless, it is biologically inactive and needs to be transported to the

kidney where it will be converted to its active form, 1,25-dihydroxyvitamin D,

abbreviated as 1,25(OH)2D. 1,25(OH)2D is being produced within a specific finite

amount, regulated by the serum concentration of parathyroid hormone, calcium, and

phosphorus. The Vitamin D status of a person plays big role in maintaining bone health

and health in general. The role it assumes in bone calcium absorption from the intestine

is known and requires no further discussion. It is well documented that Vitamin D is

associated with lowering risk for cancer and multiple other diseases like sclerosis,

diabetes, pneumonia and hypertension. It should also be recognized that every tissue in

human body possesses a Vitamin D receptor – which hints some insights to the

mechanism by which it operates.

ONCE UPON A SCIENCE

Historically, the beginning of acknowledging vitamins as integral to promoting health

could be traced back to two discoveries. One of them, was conducted by Eijkman (1980)

to study beriberi in Indonesia (then called East Dutch Indies). The disease, characterized

by lower limbs numbness and paralysis, was rather new in the Malay Archipelago,

Indonesia. Eijkman observed that the fowl raised in his laboratory, which were given

polished rice before, recovered from beriberi when the diet was changed to unpolished

rice. He then surmised that some dietary factor was missing from the polished rice

which causes beriberi. He called it the anti-beriberi or the antineuritic which

corresponds to nowadays Vitamin B1. The study demarcates a new angle of thought

that “many of the commoner disease of civilized man had a dietetic factor as a

basis”Error! Reference source not found.

Sifting through the history, in the beginning of the 20th century Industrial Revolution, a

pandemic was observed: more than 80% of the children in Europe developed a

grotesque health condition known as rachitis or rickets. Responding to the situation,

researchers started to focus on curbing the issue. It was Mellanby (1920) who first

described Vitamin D in an experiment designed by raising up dogs in captivity. He found

out that the dogs developed beriberi, marked by the poor function of hind limb, when

fed on diet of porridge. The condition, however, could be remedied by starting them on

cod liver oil. Using the same logic that of Eijkman’s, he drew a conclusion from these

observations that rickets was due to the lacking of certain dietetic factor, the Vitamin D.

In 1921, Hess and Unger demonstrated that children suffering from rickets improved

significantly when exposed to sunlight on the roof of New York City hospital. In a quite

similar way, Goldblatt and Soames (1923) proved that rachitic rodents heal at par with

their counter partners on cod liver oil, when treated with by irradiation with an

ultraviolet lamp. With these discoveries as the basis, it was later confirmed that Vitamin

D is both nutrient and pro-hormone – it was a misnomer.

The irradiation technique later expanded to human before venturing to food. Initially

milk was directly irradiated with ultraviolet light before further discoveries make way to

an easier production of vitamin D from irradiation of yeast. This is the beginning of the

milk fortification program which contributed greatly to eradicating rickets. Holick (2010)

noted that this is along with the widespread of cod liver oil and that the program was so

popular that “it was added to custards, hotdogs and even beer in the US”. Later during

the 1950s, the outbreak of hypercalcemia in infants in Great Britain led to banning of

Vitamin D fortification of most food, despite being ill- to non-proven. All European

countries soon exemplify. In the following years, some classic papers which drew

conclusion of Vitamin D intoxication were produced such as paper from Narang NK

(1984); report by J. S. Adams and Gene Lee (1997); and editorial by Bernadette M.

Marriot (1997). R. Vieth (1999) from University of Toronto greatly challenges the idea of

Vitamin D intoxication by enumerating at least four experiments which agreed that as

far as 10,000 IU/d is physiologic to the human body. From here, things started to change

and people revisited the experiments and new regulations were made. Finally in 2010,

the Institute of Medicine (IOM) issued a report which acts as a guideline to Vitamin D

dosing.

From this narrative as a reference, we will examine in relatively detailed overview, few

of the aforementioned papers to have an insight on the dosing of vitamin D

recommended.

REVISITING THE SCIENCE

(i) Narang et al designed an experiment whereby 6 tuberculosis patient were given

3,800 IU/d of Vitamin D as part of the treatment for 3 months. The study reported a

mean of serum calcium more than 11mg/dL or 2.25 mmol/L (mild hypercalcemia is

defined as >2.5 mmol/L) being observed. The intake was defined as the lowest observed

adverse effect level (LOAEL). It was later lowered by 20% and became the no observe

adverse effect level (NOAEL). The report, The role of Vitamin D in Tuberculosis was

published in 1984. It was believed that low Vitamin D concentration in TB patient make

way for the its progression since it is dealt with through the type IV immunity which

requires adequate Vitamin D to perform wellError! Reference source not found..

The paper however reported only the electrolyte changes without explicitly verifying the

changes to the concentration of 25(OH)D which led to questioning the integrity of the

experiment. Previously, however, an equivalent study reported by Subhash C. Sharma

reported the distinction between TB and COPD patients’ reaction to vitamin D intake.

About 15.5% of the TB patient developed hypercalcemia (>2.63 mmol/L in 2 or more

occasions) while the rest did not. It should be noted here, however, those hypercalcemic

patients were on higher supplements than the rest, up to 3,800 IU/d , compared with

400 IU/d. Alternative explanation like involvement of bone and renal TB; or increase

bone resorption due to decrease in Prostaglandin E degradation out of intensive lung

deterioration was not supported since not every patient developed the condition. A

positive relationship between higher Vitamin D supplement and hypercalcemia, hence,

was established along with Vitamin D sensitivity. However, this is true pertaining to the

TB patients only since none of the COPD counter partners being hypercalcemic. This was

reported in Serum calcium in pulmonary tuberculosis year 1981.

(ii) In 1997, Adams and Lee produced a paper reporting a research designed by case

series conducted between November 1992 and November 1993, surveying a total of 39

patients referred to Bone Centre, Los Angeles. 4 of them were found to have

hypercalciuria and elevated serum 25(OH)D with values ranging from 132 – 222 nmol/L.

None of the patients were unknowingly consumed more than 1200 IU/d (30μg) of

vitamin D or took other medication known to alter skeletal metabolism. After correction

were made, the hypercalciuria resolved; serum level of 25(OH)D returned to normal and

prospective study about 3 years showed increase in bone density with exclusive calcium

supplement.

It should be notified that Adam and Lee had lowered the upper limit of normal serum

level of 25(OH)D from >200 nmol/L to 125 nmol/L; and the lower limit were assigned at

22 nmol/L. Although there are numerous studies that contradict this such that the upper

limit were set at >200 nmol/L and lower limit no less than 30 nmol/L, it is of technical

definition which should not be overly debated as it could be mathematically

appropriated. Instead, a better appreciation should be given to the relationship

portrayed by the research between vitamin D intake, the serum level of 25(OH)D, and

hypercalciuria events. It is established that the first sign of hypervitaminosis D is

hypercalciuria; and since the condition subsided when the vitamin D supplements were

stopped; and the bone did gain steady mass increment with exclusive calcium

supplement; it could be said that a positive correlation is observed between them.

However, another study conducted by Melissa K. Thomas et al showed that a routine

vitamin D intake of >20μg led to the serum level of 25(OH)D around 22ng/ml or 55

nmol/L. In fact, out of 290 subjects, 164 (57%) of them developed hypovitaminosis D,

which is in contradiction to Adam and Lee’s findings. Nevertheless, the target of these

two experiment were different. Melissa et al focused on inpatient in seasonal nadir

while Adams and Lee followed their subjects for three years which underline the normal

activity of the patients. Hence, it is sound to say that that of Adam and Lee’s is more

convincing.

(iii) Finally in our historical scope comes The 2011 Report on Dietary Reference Intakes

for Calcium and Vitamin D from the Institute of Medicine: What Clinicians Need to Know

done by the Chair of the Institute of Medicine Committee to Review Dietary Reference

Intakes for Vitamin D and Calcium herself, Dr. A. Catharine Ross. The report was done to

update the 1997 issue. It includes 14 scientists assisted with experienced IOM staff

members. From March 2009 to November 2010, the Committee conducted extensive

and comprehensive review of existing evidence of calcium and vitamin D benefit in

relation to various health outcomes.

It was summarized that the Committee supports key role of calcium and vitamin D in

skeletal health but holds that there is insufficiency to establish any extraskeletal

benefits. Thus, the recommendation was that, no more than 600 IU/d were given to

those 1 – 70 years old and 800 IU/d for 71 and older. This corresponds to 50 nmol/L of

25(OH)D which, according to them, meet the requirement of 97.5% of the population,

with minimal sun exposure being factored in. Greater dosage does not necessarily bring

about any benefits and might cause detrimental effects as curvilinear associations were

observed with greater vitamin D intake. The report also concluded that the prevalence

of vitamin D deficiency has been overestimated.

It should be noted here that, whenever the term ‘benefit’ is used within the IOM report,

it refers exclusively to the positive impact onto the bone health which justifies such

lower dosage recommended. However, taken at face value, it seems that the Committee

is suggesting that babies and adults having the exact same dose of vitamin D

supplement. This is something quite bizarre taking into consideration the growth spurts

in babies which requires more calcium for bone building.

CONCLUSION

The objective of this paperwork is to induce critical thinking among the medical students

upon countering controversial medical issues. In order to achieve it, the key principles to

critically read the medical journals are extracted from the 3 topics discussed before.

In the discussion regarding the controversy of h. pylori discovery, the key principle being

used is criticizing the history development of acid against bacteria in their contribution

to peptic ulcer disease. Then, the focus was on the triangle conflict between A. Stone

Freedberg, E. D. Palmer and Marshall with Barren. We highlighted their method of

experiment's investigation, way of proving their research and fallacy in proving the

association between the inflammation caused by the bacteria and manifestation of

peptic ulcer.

After that, we presented fluoride as the topic of discussion. In this topic, our main

attentions are the relevant factors affecting the validity of the finding of the

experiments. The factors mentioned are the age of the subjects, human-animal dose

relativity, efficacy of fluoride now and then and form of fluoride received by the subject

in different circumstances.

The last topic chosen was the determination of valid dosage of vitamin D required in

human. Here, the measured item must resemble the objective of the experiment.

Furthermore, it is advisable for us to cross-check for there may be equivalent

paperworks with contradicting results. We must check for the governing principle that

explains the contradiction. Lastly, we need to justify recommendations and conclusions

based on initial assertion of the paper.

These are some of the key principles outlined by us in order to manifest the way of

thinking critically upon countering controversial medical issues. We hope most of the

medical students are enlightened in the field of critical reading due to the result of

finishing this paperwork.

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