PellagraFrom Wikipedia, the free encyclopedia

Pellagra

Classification and external resources

Pellagra sufferer with skin lesions

ICD-10 E 52

DiseasesDB 9730

MedlinePlus 000342

eMedicine ped/1755

MeSH C18.654.521.500.133.699.529

Pellagra is a vitamin deficiency disease most commonly caused by a chronic lack ofniacin (vitamin B3) in

the diet. It can be caused by decreased intake of niacin ortryptophan,[1] and possibly by excessive intake

of leucine.[2] It may also result from alterations in protein metabolism in disorders such as carcinoid

syndrome. A deficiency of the amino acid lysine can lead to a deficiency of niacin, as well.[3]

Contents

  [hide] 

1   History

2   Epidemiolog

y

3   Symptoms

4   Pathophysiol

ogy

5   Prognosis

6   See also

7   References

8   Further

reading

9   External

links

[edit]History

The traditional food preparation method of maize ("corn"), nixtamalization, by native New World cultivators

who had domesticated corn required treatment of the grain with lime, analkali. The lime treatment now has

been shown to make niacin nutritionally available and reduce the chance of developing pellagra.[4] When

maize cultivation was adopted worldwide, this preparation method was not accepted because the benefit

was not understood. The original cultivators, often heavily dependent on maize, did not suffer from

pellagra; it became common only when maize became a staple that was eaten without the traditional

treatment.

Pellagra was first described for its dermatological effect in Spain in 1735 by Gaspar Casal. He explained

that the disease causes dermatitis in exposed skin areas such as hands, feet and neck and that the origin

of the disease is poor diet and atmospheric influences.[5] His work published in 1762 by his friend Juan

Sevillano was titled ‘Historia Natural y Medicina del Principado de Asturias’ or Natural and Medical History

of the Principality of Asturias (1762). This led to the disease being known as "Asturian leprosy", and it is

recognized as the first modern pathological description of a syndrome.[6] It was an endemic disease in

northern Italy, where it was named pelle agra (pelle = skin; agra = sour) by Francesco Frapoli of Milan.[7] In

the 19th century Roussel started a campaign in France to restrict consumption of maize and eradicated the

disease in France, but it remained endemic in many rural areas of Europe.[8] Because pellagra outbreaks

occurred in regions where maize was a dominant food crop, the belief for centuries was that the maize

either carried a toxic substance or was a carrier of disease. Pellagra was also conjectured to be carried by

insects. Later, the lack of pellagra outbreaks in Mesoamerica, where maize is a major food crop, led

researchers to investigate processing techniques in that region.

Dr. Joseph Goldberger

Pellagra was studied mostly in Europe until the late 19th century when it became an epidemic especially in

the southern United States.[9] In the early 1900s, pellagra reached epidemic proportions in the American

South. Between 1906 and 1940 more than 3 million Americans were affected by pellagra with more than

100,000 deaths, yet the epidemic resolved itself right after dietary niacin fortification.[10] Pellagra deaths in

South Carolina numbered 1,306 during the first ten months of 1915; 100,000 Southerners were affected in

1916. At this time, the scientific community held that pellagra was probably caused by a germ or some

unknown toxin in corn.[11] The Spartanburg Pellagra Hospital in Spartanburg, South Carolina, was the

nation's first facility dedicated to discovering the cause of pellagra. It was established in 1914 with a special

congressional appropriation to the U.S. Public Health Service (PHS) and set up primarily for research. In

1915, Joseph Goldberger, assigned to study pellagra by the Surgeon General of the United States, showed

it was linked to diet by inducing the disease in prisoners, using the Spartanburg Pellagra Hospital as his

clinic. By 1926, Goldberger established that a balanced diet or a small amount of brewer's

yeast [12]  prevented pellagra.

Goldberger experimented on 11 prisoners. Before the experiment, the prisoners were eating fruits and

vegetables from the prison garden. Goldberger started feeding them only corn. About two weeks into the

experiment, the prisoners complained of headaches, confusion, and loss of appetite. In the third week,

seven of the 11 broke out in pellagra, and two prisoners begged for release. Goldberger cured them,

feeding them fruits and vegetables again, and gave them their freedom. In 1920’s he connected pellagra to

the diet of rural areas with corn-based diets rather than infection, contrary to the common medical ideas of

that time.[13][14] Despite all his efforts few physicians took up his ideas due to necessity of social reform,

especially in the land system of that time, which led to many avoidable deaths and stereotypes.

[15] Goldberger is remembered as the "unsung hero of American clinical epidemiology".[16] However, he

failed to identify a specific element whose absence caused pellagra.

In 1937, Conrad Elvehjem, of Madison, Wisconsin, showed the vitamin niacin cured pellagra (manifested

as black tongue in dogs). Later studies by Dr. Tom Spies, Marion Blankenhorn, and Clark Cooper

established that niacin also cured pellagra in humans, for which Time Magazine dubbed them its 1938 Men

of the Year in comprehensive science.

Research conducted between 1900 and 1950 found the number of cases of women with pellagra was

consistently double the number of cases of afflicted men.[17] This is thought to be due to the inhibitory effect

of estrogen on the conversion of the amino acid tryptophan to niacin,[18] or to the differential and unequal

access to quality foods within the household. Some researchers of the time gave a few explanations

regarding the difference.[19] As primary wage earners, men were given consideration and preference at the

dinner table. They also had pocket money to buy food outside the household. Women gave quality protein

foods to their children first. Women also would eat after everyone else.[citation needed]

Gillman and Gillman related skeletal tissue and pellagra in their research in South African Blacks. They

provide some of the best evidence for skeletal manifestations of pellagra and the reaction of bone in

malnutrition. They claimed radiological studies of adult pellagrins demonstrated marked osteoporosis. A

negative mineral balance in pellagrins was noted, which indicated active mobilization and excretion of

endogenous mineral substances, and undoubtedly impacted the turnover of bone. Extensive dental caries

were present in over half of pellagra patients. In most cases, caries were associated with "severe gingival

retraction, sepsis, exposure ofcementum, and loosening of teeth".[20] Pellagra is no longer common in the

United States.

[edit]Epidemiology

Pellagra can be common in people who obtain most of their food energy from maize ("corn" in North

American English), notably ruralSouth America, where maize is a staple food. If maize is not nixtamalized,

it is a poor source of tryptophan, as well as niacin. Nixtamalization corrects the niacin deficiency, and is a

common practice in Native American cultures that grow corn. Following the corn cycle, the symptoms

usually appear during spring, increase in the summer due to greater sun exposure, and return the following

spring. Indeed, pellagra was once endemic in the poorer states of the U.S. South, such as Mississippi and

Alabama, as well as among the residents of jails and orphanages as studied by Dr. Joseph Goldberger.

Pellagra is common in Africa, Indonesia, North Korea,[21] and China. In affluent societies, a majority of

patients with clinical pellagra are poor, homeless, alcohol-dependent, or psychiatric patients who refuse

food.[22] In other countries such as the Netherlands and Denmark, even with sufficient intake of niacin,

cases have been reported. In this case deficiency might happen not just because of poverty or malnutrition

but secondary to alcoholism, drug interaction (psychotropic, cytostatic, tuberclostatic or analgesics), HIV,

vitamin B2 and B6 deficiency, or malabsorption syndromes such as Hartnup and carcinoid.[23][24][25][26][27][28][29]

[30] For example anti-tuberculosis medication tends to bind to vitamin B6 and reduce niacin synthesis; in

carcinoid syndrome there are neuroendocrine tumors along the GI tract that use tryptophan as the source

for serotonin production, which limits the available tryptophan for niacin synthesis. Hartnup syndrome on

the other hand reduces niacin or tryptophan absorption. Pellagra was common among prisoners of Soviet

labor camps (the Gulag). It can be found in cases of chronic alcoholism. In addition, pellagra, as a

micronutrient deficiency disease, frequently affects populations of refugees and other displaced people due

to their unique, long-term residential circumstances and dependence on food aid. Refugees typically rely

on limited sources of niacin provided to them, such as groundnuts; the instability in the nutritional content

and distribution of food aid can be the cause of pellagra in displaced populations. Despite all the knowledge

about pellagra, there are a few recent outbreaks in countries such as Angola, Zimbabwe and Nepal.[31][32]

[33] In Angola specifically, recent reports show a similar incidence of pellagra since 2002 with clinical

pellagra in 0.3% of women and 0.2% of children and niacin deficiency in 29.4% of women and 6% of

children related to high untreated corn consumption.[33] WHO reported the highest niacin deficiency related

deaths in South Africa (2.8 per million), Venezuela and Brazil in 2004.[34]

[edit]Symptoms

The dermatologic features of this disorder include desquamation, erythema, scaling, and keratosis of sun-exposed

areas, all of which this patient had.

Pellagra is classically described by "the four D's": diarrhea, dermatitis, dementia anddeath.[35] A more

comprehensive list of symptoms includes:

High sensitivity to sunlight

Aggression

Dermatitis , alopecia, edema

Smooth, beefy red glossitis

Red skin lesions

Insomnia

Weakness

Mental confusion

Ataxia , paralysis of extremities, peripheral neuritis

Diarrhea

Dilated cardiomyopathy

Eventually dementia

Frostig and Spies (acc. to Cleary and Cleary) described more specific psychological symptoms of pellagra

as:[36]

Psychosensory disturbances (impressions as being painful, annoying

bright lights, odors intolerance causing nausea and vomiting, dizziness

after sudden movements)

Psychomotor disturbances (restlessness, tense and a desire to quarrel,

increased preparedness for motor action)

Emotional disturbances

Despite clinical symptoms, blood level of tryptophan or unrinary metabolites such as 2-pyridone/N-

methylniacinamide ratio <2 or NAD/NADP ratio in erythrocytes could be used to diagnose pellagra.

Diagnosis could be confirmed after rapid improvements in the symptoms in patients using high doses of

niacin (50–500 mg/day) or niacin enriched food.[37]

[edit]Pathophysiology

Pellagra can develop according to several mechanisms, all of which ultimately revolve around niacin

deficiency. The first is simple dietary lack of niacin. Second, it may result from deficiency of tryptophan,

[1] an essential amino acid found in meat, poultry, fish, and eggs.[38] that the body converts into niacin. Third,

it may be caused by excess leucine, though the relationship is unclear.[2]

Alterations in protein metabolism may also produce pellagra-like symptoms. An example is carcinoid

syndrome, a disease in whichcarcinoid tumors produce excessive serotonin. In normal patients, only one

percent of dietary tryptophan is converted to serotonin; however, in patients with carcinoid syndrome, this

value may increase to 70%. The diversion of tryptophan to making serotonin in patients with metastatic

tumors can result in tryptophan deficiency. Carcinoid syndrome thus may produce decreased protein

synthesis, niacin deficiency, and clinical manifestations of pellagra.

[edit]Prognosis

Untreated, the disease can kill within four or five years. Treatment is with nicotinamide, a chemical related

to niacin. The frequency and amount of nicotinamide administered depends on the degree to which the

condition has progressed.

[edit]See also

Central chromatolysis

Hartnup disease

Unethical human experimentation in the United States

[edit]References

1. ^ a b Pitche P (2005). "Pellagra". Sante 15 (3): 205–8.PMID 16207585.

2. ^ a b Bapurao S, Krishnaswamy K (1978). "Vitamin B6 nutritional status

of pellagrins and their leucine tolerance". Am J Clin Nutr 31 (5): 819–

24. PMID 206127.

3. ̂  "Lysine | amino acid health benefits, dietary sources, side effects".

Vitamins-supplements.org. Retrieved 2012-07-31.

4. ̂  Rajakumar, K (2000). "Pellagra in the United States: A Historical

Perspective". Southern Medical Journal 98 (3): 272–

277. ISSN 00384348. PMID 10728513.

5. ̂  Casal G. The natural and medical history of the principality of the

Asturias. In: Classic Descriptions of Disease (Major RH, ed.), 3rd edn.

Springfield, IL: Charles C Thomas Publisher, 1945; 607–12.

6. ̂  Stratigos JD, Katsambas A (1977). "Pellagra: a still existing

disease". Br. J. Dermatol. 96 (1): 99–106. doi:10.1111/j.1365-

2133.1977.tb05197.x. PMID 843444.

7. ̂  "Definition of Pellagra". MedicineNet.com. Retrieved 2007-06-18.

8. ̂  Semba, R. D. (2000). "Theophile Roussel and the elimination of

pellagra from 19th century France." Nutrition 16(3): 231-

233.http://www.ncbi.nlm.nih.gov/pubmed/10705082?dopt=Citation

9. ̂  Sydenstricker, V. P. (1958). "The history of pellagra, its recognition

as a disorder of nutrition and its conquest." Am J Clin Nutr 6(4): 409-

414.http://www.ncbi.nlm.nih.gov/pubmed/13559167?dopt=Citation

10. ̂  Bollet, A. J. (1992). "Politics and pellagra: the epidemic of pellagra in

the U.S. in the early twentieth century." Yale J Biol Med 65(3): 211-

221.http://www.ncbi.nlm.nih.gov/pubmed/1285449?dopt=Citation

11. ̂  Bollet A (1992). "Politics and pellagra: the epidemic of pellagra in

the U.S. in the early twentieth century". Yale J Biol Med 65 (3): 211–

21. PMC 2589605. PMID 1285449.

12. ̂  Swan, Patricia (2005). "Goldberger's War: The Life and Work of a

Public Health Crusader (review)". Bulletin of the History of

Medicine (The Johns Hopkins University Press) 79 (1): 146–

7. doi:10.1353/bhm.2005.0046.

13. ̂  Goldberger, J. and G. A. Wheeler (1990). "Experimental pellagra in

the human subject brought about by a restricted diet. 1915." Nutrition

6(5): 357-360; discussion 361-

352.http://www.ncbi.nlm.nih.gov/pubmed/2134557?dopt=Citation

14. ̂  Goldberger, J. (2006). "The etiology of pellagra. 1914." Public

Health Rep 121 Suppl 1: 77-79; discussion

76.http://www.ncbi.nlm.nih.gov/pubmed/16550768?dopt=Citation

15. ̂  Wolf, R., E. Orion, et al. (2002). "Miscellaneous treatments, II: niacin

and heparin: unapproved uses, dosages, or indications." Clin

Dermatol 20(5): 547-

557.http://www.ncbi.nlm.nih.gov/pubmed/12435525?dopt=Citation

16. ̂  Elmore, J. G. and A. R. Feinstein (1994). "Joseph Goldberger: an

unsung hero of American clinical epidemiology." Ann Intern Med

121(5): 372-375.http://www.ncbi.nlm.nih.gov/pubmed/8042827?

dopt=Citation

17. ̂  Miller DF (1978). "Pellagra deaths in the United States". Am. J. Clin.

Nutr. 31 (4): 558–9. PMID 637029.

18. ̂  Brenton, Barrett (2000). "Pellagra, Sex and Gender: Biocultural

Perspectives on Differential Diets and Healths".Nutritional

Anthropology 23 (1): 20–24.doi:10.1525/nua.2000.23.1.20.

19. ̂  Carpenter, Kenneth (1981). Pellagra. Stroudsburg, Pa: Hutchinson

Ross Pub. Co. ISBN 0-87933-364-2.

20. ̂  Gillman, Joseph; Gillman, Theodore (1951). Perspectives in Human

Malnutrition: A Contribution to the Biology of Disease from a Clinical

and Pathological Study of Chronic Malnutrition and Pellagra in the

African. New York, New York: Grune and Stratton.

21. ̂  Harden, Blaine (2012). Escape from Camp 14: One Man's

Remarkable Odyssey from North Korea to Freedom in the West.

Viking Adult. ISBN 0670023329.

22. ̂  Jagielska G, Tomaszewicz-Libudzic EC, Brzozowska A (2007).

"Pellagra: a rare complication of anorexia nervosa". Eur Child Adolesc

Psychiatry 16 (7): 417–20. doi:10.1007/s00787-007-0613-

4. PMID 17712518.

23. ̂  Hegyi, J., R. A. Schwartz, et al. (2004). "Pellagra: dermatitis,

dementia, and diarrhea." Int J Dermatol 43(1): 1-

5.http://www.ncbi.nlm.nih.gov/pubmed/14693013?dopt=Citation

24. ̂  Prousky, J. E. (2003). "Pellagra may be a rare secondary

complication of anorexia nervosa: a systematic review of the

literature." Altern Med Rev 8(2): 180-185.

25. ̂  Pitsavas, S., C. Andreou, et al. (2004). "Pellagra encephalopathy

following B-complex vitamin treatment without niacin." Int J Psychiatry

Med 34(1): 91-95.http://www.ncbi.nlm.nih.gov/pubmed/15242145?

dopt=Citation

26. ̂  Monteiro, J. P., D. F. da Cunha, et al. (2004). "Niacin metabolite

excretion in alcoholic pellagra and AIDS patients with and without

diarrhea." Nutrition 20(9): 778-

782.http://www.ncbi.nlm.nih.gov/pubmed/15325687?dopt=Citation

27. ̂  Beretich, G. R., Jr. (2005). "Do high leucine/low tryptophan dieting

foods (yogurt, gelatin) with niacin supplementation cause

neuropsychiatric symptoms (depression) but not dermatological

symptoms of pellagra?" Med Hypotheses 65(3): 628-

629.http://www.ncbi.nlm.nih.gov/pubmed/15913906?dopt=Citation

28. ̂  Seal, A. J., P. I. Creeke, et al. (2007). Low and deficient niacin

status and pellagra are endemic in postwar Angola." Am J Clin Nutr

85(1): 218-224.http://www.ncbi.nlm.nih.gov/pubmed/17209199?

dopt=Citation

29. ̂  Oliveira, A., M. Sanches, et al. (2011). "Azathioprine-induced

pellagra." J Dermatol 38(10): 1035-

1037.http://www.ncbi.nlm.nih.gov/pubmed/21658113?dopt=Citation

30. ̂  Delgado-Sanchez, L., D. Godkar, et al. (2008). "Pellagra: rekindling

of an old flame." Am J Ther 15(2): 173-

175.http://www.ncbi.nlm.nih.gov/pubmed/18356638?dopt=Citation

31. ̂  Baquet S, Wuillaume F, Van Egmond K et al. Pellagra outbreak in

Kuito, Angola. Lancet 2000; 355:1829–30.

32. ̂  Dhakak, M., B. Limbu, et al. (2003). "A typical case of pellagra."

Kathmandu Univ Med J (KUMJ) 1(1): 36-

37.http://www.ncbi.nlm.nih.gov/pubmed/16340260?dopt=Citation

33. ^ a b Seal, A. J., P. I. Creeke, et al. (2007). "Low and deficient niacin

status and pellagra are endemic in postwar Angola." Am J Clin Nutr

85(1): 218-224.http://www.ncbi.nlm.nih.gov/pubmed/17209199?

dopt=Citation

34. ̂  World Health Organization. Pellagra and Its Prevention and Control

in Major Emergencies. WHO ⁄NHD ⁄ 00.10. Geneva, Switzerland:

World Health Organization, 2000.

35. ̂  Hegyi J, Schwartz R, Hegyi V (2004). "Pellagra: dermatitis,

dementia, and diarrhea". Int J Dermatol 43 (1): 1–

5.doi:10.1111/j.1365-4632.2004.01959.x. PMID 14693013.

36. ̂  Cleary MJ, Cleary JP (1989). "Anorexia nervosa: a form of

subclinical pellagra". Int Clin Nutr Rev 9: 137–143. ISSN 0813-9008.

37. ̂  Gehring, W. (2004). "Nicotinic acid/niacinamide and the skin."

Journal of Cosmetic Dermatology 3: 88–93.

38. ̂  Haas EM. "Vitamin B3—Niacin". Excepted from: Staying Healthy

with Nutrition: The Complete Guide to Diet and Nutritional Medicine.

Retrieved 2007-06-18.

[edit]Further reading

Hampl JS, Hampl WS (1 November 1997). "Pellagra and the origin of a

myth: evidence from European literature and folklore". J Roy Soc

Med. 90 (11): 636–9. PMC 1296679. PMID 9496281.

"Reports and Resolutions of the General Assembly of the State of

South Carolina, Regular Session Commencing January 11,

1916". Annual Report of the State Board of Health (1915-

1916). (Columbia, S.C.: Gonzales and Bryan, state printers) 4. 1916.

Beardsley E (2006). The Spartanburg Pellagra Hospital. In: The South

Carolina Encyclopedia. Columbia, S.C: University of South Carolina

Press. ISBN 1-57003-598-9.

Swain CP, Tavill AS, Neale G (September 1976). "Studies of

tryptophan and albumin metabolism in a patient with carcinoid

syndrome, pellagra, and hypoproteinemia". Gastroenterology 71 (3):

484–9. PMID 133045.

Hendrick, Burton J. (April 1916). "The Mastery Of Pellagra: The

Mysterious Disease, Almost Unknown In This Country Fifteen Years

Ago, That Now Claims 7,500 Victims A Year And Is Spreading

Rapidly". The World's Work: A History of Our Time XXXI: 633–639.

Retrieved 2009-08-04.

Kraut, Alan. "Dr. Joseph Goldberger and the War on Pellagra, By Alan

Kraut, Ph.D." Office of History, National Institutes of Health. Web. 03

Sept. 2010.

<http://history.nih.gov/exhibits/goldberger/docs/pellegra_5.htm>.

[edit]External links

wholegrain.umn.edu

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Hypoalimentation/

malnutrition

Protein-energy

malnutritionKwashiorkor · Marasmus · Catabolysis

Avitaminosis

B vitamins

B1: Beriberi/Wernicke's

encephalopathy (Thiamine deficiency) · B2: Ariboflavinosis ·B3: Pellagra (Niacin deficiency) · B6:

deficiency · B7: Biotin deficiency ·B9: Folate deficiency · B12: Vitamin B12  deficiency

Other

vitamins

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E deficiency · K: Vitamin K deficiency

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Sodium · Potassium · Magnesium · Calcium · Iron · Zinc · Manganese · Copper · Iodine · Chromium ·Molybdenum

disease)

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M: NUT cof, enz, met noco, nuvi, sysi/epon, met drug (A8

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Lecture 5: DISCOVERING NUTRITIONAL DEFICIENCY DISEASES

(Stories in the History of Medicine)

AdamBlatner, M.D.

Lecture given February, 2009; Re-posted on website August 4, 2010

This is the fifth in a series of presentations given to the February-March, 2009 session of our local lifelong learning program, Senior University Georgetown.)Other lectures in this series include: 1. Introduction and Germ Theory, plus supplementary webpages on a brief overview of the history of medicine before 1500, a brief overview of the history of medicine after 1500, and the history of microscopy. 2: Contagion, Infection, Antisepsis ; 3: The Early History of Immunology ; 4. The Discovery of Anesthesia. .. 5. This webpage (title above), and: 6: Hygiene: Cholera, Hookworm & Sanitation . 6a. Dental Hygiene and Plaque Control (Flossing)

Today we'll address the history of nutritional deficiencies. A theme here is the opening of previously unrecognized horizons. People didn't know there were subtle substances in food. We came to realize that there are stars beyond what we can see with the naked eye and forms of life too small, and similarly, there were many other subtleties that await technological enhancements to appreciate. In the field of nutrition, this involves the continuing development of equipment for testing or assaying tiny amounts of chemicals. Many of the breakthroughs in medicine were made not by physicians, but by chemists and biochemists. (Biochemistry as a field emerged only in the early 1800s when it became apparent that the chemistry of living matter was more complicated and based mainly on the properties of the carbon atom.) Before that, though, what some pioneers did was more a job for Sherlock Holmes, a process of deduction, experiment, but not fully understanding why or how it works.

The topics to be addressed today include basic protein deficiency in starvation; iron deficiency anemia; scruvy; iodine-deficiency and subsequent low thyroid functin; rickets from vitamin D deficiency; beriberi from Vitamin B1 deficiency; and pellagra from niacin deficiency---and some of the stories of the discovery of their existence. It should be noted thought that new subtle nutrients are still being discovered, or research is revealing that more or less of this or that is optimal. For example, only about 17 years ago evidence accumulated that mothers need increased folic acid to reduce the incidence of certain birth defects such as spina bifida. Now it's being added to foods!

Protein Deficiency

Our first condition to be noted is that of kwashiorkor, a disease of protein deficiency. Generally, this is associated with many other

types of nutritional deficiency, but the lack of protein has its own consequences. The muscles shrink, the hair develops a reddish tint, the liver swells

and its fat content grows to compensate for the lack of protein, which gives the impression of a fat belly---but that is not fat, it represents a liver that is diseased and not functioning properly.

One cause of kwashiorkor is of course simple famine, one of the four horsemen of the apocalypse. Let's note a point here, though: A person can become malnourished even if they are getting enough general foodstuffs in the form of simple calories. This is because there are three main categories of food: carbohydrates, fats and

proteins. Carbohdrates are mainly used for basic calories, for fuel for the cells to live. Fats are used also mainly for fuel, but also some of its components are important as building blocks; Proteins are broken down into amino acids that are mainly used for building blocks in growing new tissues or replacing old cells. We need all three types.

It's possible to have a diet that is made up mainly of calories, interestingly enough. The second is used both for fuel , the fuel and the building blocks. We need both. In the picture of the baby on the right, it was probably fed on corn mush or what some might call "empty calories." They're not empty in the sense of providing nutrition as fuel, but it doesn't adequately provide the variety of proteins and other nutrients to keep up health. This baby also has kwashiorkor, even though she isn't starving. Sadly, there are babies in poor families (and even some pampered babies in rich families who get fine sweets!) who don't get a truly balanced diet and get sick as a result!

Thus, being a little fat in cheeks and elsewhere isn't a reliable guide. This baby may have been fed mainly on corn mush. The raw creases at the edges of the mouth is called cheilosis. Other signs include the reddish hair and empty vision. Protein deficiency, kwashiorkor, leads to mild mental retardation, because the brain lacks the nutrients to work with. Thus part

of prevention is education of parents about good nutrition, and some teen parents aren't bothering to learn what they need to about child care---their babies are thus a population at risk. Indeed, one of the points of this and the next lecture is an appreciation of the nature of public health as a preventive force in society.

Iron Deficiency

In the last several centuries it seemed to be profitable to slave-owners or managers of institutions to cut costs and maximize profit by feeding their charges with the cheapest foods. As a result, children, the insane, prisoners, slaves, often soldiers and sailors too, received the most meagre rations compatible

with life.

The picture on the left shows native Indian slaves in 17th century Florida planting and hoeing. (Yes, the Spanish Conquistadores enslaved the aboriginal population! They felt entitled to do so because they were possessors of truth and goodness and the Indians were heathens who, by not being baptized, didn't merit the privileges of full humanity---i.e., it was okay to make them into slaves.) Whereas the Indians ate a varied diet based on a hunter-gatherer cultural practice, as slaves their diet became mainly maize corn, which lacks a number of nutrients---iron being one of them.

As a result, children struggle with chronic iron deficiency. Iron is needed to build blood cells, and if there isn't enough in the diet, the body works overtime. The bone marrow where blood cells are manufactured expands. For example, while the skull doesn't usually have much space for marrow between the outer and inner

external plates, in chronic anemia this space expands and the bone becomes strangely porous---a condition known as porotic hyperostosis (bony overgrowth). To the right is a picture of the skull of one of the children of those 17th century Florida Indians, indicating that chronic iron-deficiency anemia had become common.

Iron and Hemoglobin

The mineral iron is quite common, and indeed is one of the main components of the planet's core, accounting in great part for the Earth's magnetic field. The iron atom figures in a number of biological key compounds and enzymes, especially those that derive from the "porphyrin" molecule shown on the left. (I have always been

impressed with beauty of the form of this molecule!) The iron is the red part surrounded by the blue nitrogen atoms, and located so that depending on minute fluctuations of acidity or alkalinity, it tends to either attract a molecule of oxygen and release carbon-dioxide (as happens in the slightly less acidic environment of the lungs) or vice versa: In the slightly more acidic environment of the tissues, where new oxygen is needed and carbon dioxide is building up, there the hemoglobin molecule lets go of its loosely bound oxygen and binds instead to carbon dioxide. Thus, hemoglobin is the key messenger substance of blood, the blood corpuscle is its package, and iron is its core component. If there isn't enough iron, the body can't easily build up the rest of the system, the blood cells become pale---not enough red-colored molecules of hemoglobin---and the result is anemia.

In anemia, the tissues aren't getting enough oxygen and the person feels bad, tired, and exertion quickly becomes exhausting. Not understanding that slaves and other poorly nourished people really were suffering with a handicap of low blood hemoglobin, their seeming sluggishness was interpreted as laziness, "shiftlessness," and proof that they were unworth

of respect. This reinforced the illusions of righteousness of the class of people who exploited their labor. This dynamic still goes on in many parts of the world today.

With anemia, the problem is fatigue. Since no one listened to complaints, the fatigue was interpreted as what? Right, laziness. That proves these people are unworthy, not energetic, and therefore unworthy of moral respect. It’s right that they be treated as less than full persons. No-account, lazy, worthless, blame-worthy—bad, not sick.

Treatment

Here and there in the history of medicine there were physicians who prescribed something containing iron.

The astute 17th century English physician Thomas Sydenham was wary of many traditional theories and treatments---generally tried to avoid bleeding, leeches, the use of mercury-containing drugs, and the like. He found that pale, weak people would often respond well to a tonic made by steeping iron filings into a kind of tea.

Gradually, though, mainly near the beginning of the 20th century, when a variety of biochemists were exploring all sorts of nutrients, the value of iron became more established as a remedy for anemia. This was found to be fairly common, in fact. Some girls in the 19th century were diagnosed with "chlorosis"---a condition that has not been diagnosed for over eighty years! It is based on the greenish color of chlorine---related also to the green of the biological enzyme chlorophyl (remember those green gums in the 1950s?) . In retrospect, this condition may have been a mixture of psychosomatic symptoms, some

anorexia, anemia due to menstruation without a compensatory diet, tight clothing, and so forth. Some of these symptoms may have been overlooked also because bleeding was still a common treatment, and being somewhat anemic was even a little fashionable.

Scurvy: Vitamin C Deficiency

Another condition described centuries ago and not correctly understood was the disease called scurvy. It was prevalent among a variety of groups of people who had been restricted to a narrow range of food, generally not including fresh fruits and vegetables. Prisoners, slaves, soldiers

on long campaigns, poor people or children living in asylums, orphanages, or institutions, and especially sailors---all were not uncommonly afflicted with scurvy. It's been estimated that, reviewing the losses on returning ships, possibly more than a million sailors died from scurvy during the thousands of voyages that were undertaken between 1500 and 1830! Their diet had little that would provide the proper nutrients, you see: It consisted of salted meats (bacon or fish), old cheese, dried beans or lentils, occasional oatmeal or other cereals, hardtack (a dense, dry biscuit), water, beer, or "grog," which had a higher level of alcohol than beer.

Vitamin C is needed for connective tissues to form with some strength. So one sign is that the

skin has little blue-red places where blood leaks out from fragile capillaries, or larger areas of subdermal (under-the-skin) bleeding that looks like a bad bruise. The gums become tender---there's just little resistence to the prevalence of gum disease (see the explanation of that in the next lecture-addendum).

Really, only small amounts of vitamin C are needed, and a deficiency takes months to appear, unless one has already been marginally malnourished.

For soldiers and especially sailors on many month-long or longer expeditions, biscuits can give enough calories, but those in themselves are not sufficient. Gradually, they begin to tire easier, and have other symptoms. As with iron deficiency, their upper-class commanders just thought they were lazy. After six months, the deficiencies show: The body’s capacity to resist infection plummets. Folks die from secondary infection, and sometimes from internal bleeding, because Vitamin C helps the tissues be firm. Without it, tiny blood vessels break down and people start to get small bruises spontaneously, bruise easier, and periodontal disease—gums—also bleed and get infected. As teeth have problems, other types of malnutrition also occur.

I recently read a case study about an overly picky and obsessive child — a toddler, actually—who was permitted by his conflict-avoiding parents to restrict his diet. He'd tantrum if pushed to eat beyond his familiar range. As a result, this child developed a variety of symptoms for which he was medically evaluated thoroughly at some of the top hospitals in the area. They came up with a variety of rather rare diagnoses. But no one had taken a careful dietary history until finally someone did and recognized that scurvy should be included in the differential diagnosis. A trial of larger amounts of vitamin C began to reverse his symptoms, and this was then organized into a continuing recovery program that also included psychiatric treatment for his obsessions.

Another case I heard of is that of one of these silicon valley geeks who

worked late hours and relied on those cheese and cracker snacks and coffee that you can get from the machines in the break room— and he, too, came down with early symptoms of scurvy—and was misdiagnosed for a time and finally correctly diagnosed. But a few hundred years ago they didn’t know about nutritional deficiencies at all.

James Lind (1716-1794)

This pioneer in the history of medicine was a ship's surgeon in the British Royal Navy for nine years (1739-48), then shifting over to work in the Royal Naval Hospital. Lind became interested in scurvy, did some research, considered that it might have to do with the diet, and tried a variety of different diets. The ones that included fresh citrus juices clearly had the best response. Lind acknowledged in his 1754 treatise that others had also come to think this way

about fresh fruits, such as Sir Richard Hawkins 1593, Commodore James Lancaster in 1636 and others. I'm not sure if Lind

knew of the experience of the explorer Jacques Cartier in northeast Canada in 1535 (picture at right): Many of his men were afflicted with scurvy, and the local indigenous tribes knew a treatment for this: A tea of pine needles. It worked because all sorts of fresh fruits and vegetables are fairly rich in ascorbic acid---though at the time we didn't know what that substance was!.

At any rate, Lind did a number of experiments on sailors with scurvy, trying different diets:

An associated story is that his findings were not immediately accepted, and indeed, were not really implemented until over forty years later, when the Admiralty made a rule that all sailors would henceforth have citrus fruits included in their diets---whence comes the nickname for English sailors as "limeys" ! This shift may well have had a positive impact on the status of the naval forces that struggled with Napoleon's navy at the battle of Trafalgar and in other naval battles. Other countries such as France had not made this adjustment and continued to suffer from scurvy.

Another interesting twist: Around 1800 the potato came into much wider use in the diet of people in Ireland and Great Britain: Potatoes have only a small amount of Vitamin C, but this can be enough to sustain the body's needs, so again, scurvy began to drop away as a condition. (One of the consequences of the great potato blight in Ireland was not only famine, but also scurvy.)

Scurvy was also a danger on the arctic explorations in the late 19th

and early 20th century, and here is a picture of some men in 1875 getting their lime juice rations: Casimir Funk in 1912 worked on the idea of vitamins, noting their amine base, and

the need small amounts of these substances---he was originally writing about thiamine (the suffix -amine tends to refer to a chemical with an active nitrogen-hydrogen component), as will be discussed further on in the section on beriberi. But Funk also presciently suggested that a lack of

these substances might well be at the root of such conditions as beriberi, scurvy, pellagra, and rickets!

Interestingly, it wasn’t until the late 1920s and 1930s that ascorbic acid was identifiedAlbert Szent-Györgyi (his 1948 photo on the right) was awarded the 1937 Nobel Prize in Medicine "for his

discoveries in connection with the biological combustion processes, with special reference to vitamin C and the catalysis of fumaric acid". He also identified many components and reactions of the citric acid cycle independently from Hans Adolf Krebs.

Iodine deficiency and Thyroid Function

Another previously unappreciated mineral deficiency involves the element of iodine. This lack makes it difficult for the thyroid gland to manufacture enough thyroxin, a horomone that helps in the process of basic metabolism, the chemical processes that maintain life. Too little thyroxine and the person develops hypothyroidism or myxedema, a sluggishness

of mind and body that comes from a reduced metabolism. Iodine is a common element in seawater and fish, but in inland areas, the iodine tends to have been washed away with the

millennia of rain and rivers, so areas such as Switzerland in Europe or Michigan in the United States have little iodine in the soil or the growing foods. Before iodine fortification of salt and food, people in such regions (and even today in many other areas of the world that don't have iodine supplementation), people would get large lumps in their neck (which comes from an overgrowth of the thyroid gland---trying to make more thyroid, even in the face of the lack of a key building block---iodine, much as I described above how in iron deficiency the bone marrow also expands and distorts its surroundings). The overgrowth looks like a lump in the neck that's called "goiter" (two examples in photos on the left).

Goiter is disfiguring, but what's even worse is a condition that happens to the babies of mothers with not enough thyroid. They have a characteristic appearance that comes from a growth delay. If it is not corrected, they grow up stunted in height and also mentally retarded! This condition is

known ascretinism, and the children called cretins. If the children are treated early with thryroid hormone and given adequate iodine in their diets, as you may see in the picture on the left, some or much of this mental retardation can be reversed and they change their appearance! In most cases, goiter of short duration also can be treated with iodine supplementation in the diet.

If goiter is untreated for around five years, however, iodine supplementation or thyroxine treatment may not reduce the size of the thyroid gland because the thyroid is permanently damaged.

Near the end of the 19th century the use of extracts of thyroid was found to help low thyroid conditions, and also biochemists noted that the thyroid gland was rich in iodine. The introduction of iodized salt since the around the 1920s has eliminated this condition in many affluent countries. However, in Australia, New Zealand, and several European countries, iodine deficiency is a significant public health problem. It is more common in poorer nations. While noting recent progress, the main medical journal in Great Britain, The Lancet, editorialized, "According to the World Health Organization (WHO), in 2007 nearly 2 billion individuals had insufficient iodine intake, a third being of school age. ... Thus iodine deficiency, as the single greatest preventable cause of mental retardation, is an important public-health problem." Another complicating factor comes from the way public health initiatives to lower the risk of cardiovascular disease have resulted in lower discretionary salt use at the table. Also, with a trend towards consuming more processed foods, the non-iodized salt used in these foods also means that people are less likely to obtain iodine from adding salt during cooking.

Finally, the thyroid was one of the earlier glands to have its function recognized, though that was only in the late 19th century. Most glands we know about---tear ducts, sweat glands, and even the mucus-secreting tissues of the nose or windpipe---are "exo-crine"---meaning they secrete to the outside (exo-). Claude Bernard (picture, right) in the mid-1800s began to explore the way some organs such as the liver or pancreas secrete inside the body (though such bile and digestive secretions are technically also exocrine. But he began to consider that some organs also secrete directly into the bloodstream---and that's where the endo-crine organs began to be understood---organs such as the thyroid, adrenals, and others.

Rickets: A Disease Arising from a Deficiency of Vitamin D

This disease was noted in the 17th century, but became more common when increasing numbers of people moved from the farm---where kids played outdoors and got more sunlight---to the city, where a child might help earn a living by working indoors. It was easy, also, to live so much in the shadows in a smoggy city that again there's not much sunlight---and sunlight stimulates the production of Vitamin D in the skin. So for shut-ins or people in the

northern climates who couldn’t get it in milk, rickets became rather common. (The adult form of vitamin D deficiency is osteomalacia, a word that hints at the main pathology: The bones "osteo" become more soft ("-malacia) and other problems arise from this! Also, a diet that includes milk also includes calcium, which helps Vitamin D be absorbed; in turn, Vitamin D helps calcium be absorbed! Vitamin D also helps regulate the levels and use of calcium, but sadly many people get insufficient doses of either.

Another problem is that girls tend to get pelvic deformities that then increase significantly the likelihood of complications of delivery, requiring the use of forceps or sometimes resulting in the death of the baby and mother. The frequency of such problems (secondary to rickets) increased the use of male physicians as obstetricians, and the decline of the role and influence of the midwife.

Vitamin D is present in significant amounts in cod liver oil (also Vitamin A). When I was a kid I was given cod-liver-oil by my mom. It was a fashionable supplement in the 1920s through the 1940s, before the Vitamins were synthesized and included in many fortified foods. Though it didn't taste good, cod liver oil was recommended for rickets treatment as early as 1789 by Thomas Percival in England, though this treatment wasn't widely recognized. Dickens’ London was prime territory for rickets and Tiny Tim may have been suffering from it.

In the American South, an interesting problem came up: Melanin in the skin blocks ultra-violet light, so African-Americans only absorb about a third compared with caucasians. So those who work indoors or in overcasts conditions were prone to rickets, and some doctors even came to think of it as a disease of slaves! Even as late as the 1950s more black women had obstetrical problems due to deformed pelvises due to low-grade rickets, and as late as 1977 a national study of black pre-schoolers found a very high incidence of at least sub-clinical rickets. Also, the full body clothing of some Muslim women in some cultures is also associated with increased rickets. In Ethiopia, full swaddling of babies again leads to higher incidence of rickets in children there. The problem with some northern animal livers is that they are so rich in Vitamins A and D that they can make you sick---

it's called "Hyper-vitaminosis"---applicable only to the fat-soluble vitamins---and if you have a nice meal of polar bear liver it can kill you!

A little chronology: In 1915, McCollum, Davis & Kennedy descibed vitamins A and B, though sub-types were soon discerned in the following years.

In 1917, biochemists discovered that the key agent--the Vitamin D-- in cod liver oil was the compound, cholesterin. In 1919 E. Mellanby began trying it out as a cure for rickets in animals (created experimentally). Around that time Huldschinsky demonstrated curative effect of sunlight on rickets using a quartz lamp. On the right is a photo of the use of the quartz lamp to proide artificial sunlight for children in the prevention and treatment of rickets.Around 1920 H. Steenbock in the USA developed and patented a food irradiation process using ultraviolet light, and found that common foods could protect many children against this horrible disease. By 1924, most Americans were consuming irradiated milk and bread, and within a few years rickets was nearly eradicated throughout the country. About that same time, a German scientist identified three different types of vitamin D, of which two were derived from irradiated plant sterols, and the third type from irradiated skin-this is the form we receive when we are exposed to sunshine. This information led scientists to develop a way to synthesize vitamin D, and since this was much more economical than irradiation, many food manufacturers began adding the vitamin to their products.

Beriberi: Vitamin B1 (Thiamine) Deficiency

Thiamine is found in a variety of food, more with whole grains. With rice, the vitamin is found in the pericarp or covering of the grain, which gets rubbed off in the process of polishing. Brown rice doesn't keep as well, it tends to get rancid, and the idea of polished white rice has always been

considered a refinement, eaten by the better sorts of people. If there are enough other types of food this is not a problem, but it's a bit like the problem described above with scurvy: Sailors, soldiers, others on otherwise somewhat restricted diets, if they don't get the whole rice, come down with a multi-system disease called beriberi, which is found throughout Asia in a varied population. It was common in some armies and also navies, because as with Europe, common soldiers and sailors were given rather meager rations.

Beriberi was described by the Chinese around 2700 BC, but the cause was unknown. As seen on the chart to the left, it's a multi-system disease. The fellow at the right also probably suffers from starvation---some of the prisoners of the Japanese at the end of WW2 had this condition. But other people may not be starved of protein or calories, but still become sick.

Takaki and the Japanese Navy

Beriberi was not uncommon on long naval voyages and was thought to have much in common with scurvy. As Lind did a more than a century earlier regarding scurvy, so too there was a similar controlled trial in the early 1880s in the Japanese navy. A Japanese medical officer, Kanehiro Takaki, arranged that 2 ships left Japan on similar voyages, but with different diets. The first ship served the usual fare of rice, with some vegetables and fish. The second also served the crew wheat and milk, in addition to more meat than was served on the first ship. The results were impressive with 25 deaths from beriberi on the first ship and none on the other. The Japanese Admiralty adopted the new diet for the entire navy. The problem is that the results were published in a language few people could read, and so the dissemination of knowledge was feeble---another point of this lecture series. Even today good work is not being adequately disseminated. The internet, search enginge, and more tools for translation may make this easier, but progress needs to continue. (A note: Although the Japanese became "the enemy" in the 1940s and propaganda discounted the ability of this people, it should be noted that in the late 19th and early 20th century, there were a number of scientists who traveled internationally and made significant contributions in a variety of fields!)

Christiaan Eijkman

Physicians and tropical medical specialists were wondering if this was another as yet-unrecognized type of infection, and that's what they were looking for when they sent Dr. Christiaan Eijkman, who had been trained in Robert Koch's laboratory in Germany in the new field of bacteriology (see previous and next lecture about Koch), to

the Dutch East Indies in 1887, to work in Batavia, then the capital (on what is now the island of Java). Eijkman worked to find the source of infection but was unsuccessful. One day Eijkman noted that some chickens who fed on the garbage from the hospital and the prison were moving in a jerky way that had some similarities to the kind of nerve weaknesses associated with the disease, and wondered if they might be suffering from the same germ. Then for a few months they got better. Then they got worse again. Following up on this, Eijkman discovered that the month before and during their improvement, the food they were eating contained a good deal of un-polished, brown rice. Their diet included the residue of what was fed some prisoners at a nearby jail. Then that stopped and the chickens returned to the garbage that included only polished rice. Could there be something about the rice? Following this lead, the doctor came to as sort-of-right sort-of-wrong answer: The rice, he thought, might have a toxic agent, but it was counteracted by whatever was in the brown husk. The point was that diet could be a source of disease. He published his results of many experiments in 1897 in a German journal, and for this Ejikman was later awarded the 1929 Nobel Prize in Medicine (in conjunction with the more accurate corrective work of F. G. Hopkins, noted next.) As mentioned above, Funk followed up on this in 1911, confirmed such findings in birds, and postulated substances called vital amines, later abbreviated to vitamins.

Frederick G. Hopkins

Hopkins demonstrated the need for thiamine in the diet in publications done from 1906-1912, and was a co-recipient of the 1929 Nobel Prize in Medicine for his following-up on and confirming the preliminary findings of Eijkman. This biochemist made a number of contributions in the field of nutrition, and as the awarding person at the Nobel Awards said, [You} "...demonstrated the physiological necessity of the vitamins for normal metabolism and growth, thus very

considerably extending our knowledge of the importance of vitamins for life processes as a whole."

In 1926 two biochemists called Jansen and Donath isolated a tiny amount of a substance they called aneurin but there was too little to be of much value. In 1936 thiamine was finally identified and created synthetically. Commercial production did not start until 1937 but it achieved great importance in the 1950s with the demand for the fortification of food.

Interestingly, after 1950, the growth of rice polishing mills throughout the Pacific area led to far more beriberi. As I mentioned, hand husking and threshing wasn’t as efficient and saved the vitamins. It took a lot of politics and hustling to get the companies to cut back on their efficiency, leaving enough vitamin in. Others began to introduce some artificially enriched vitamin—in the USA it was in refined flour and then re-enriching it with thiamine as a chemical— and we remember companies advertising how their bread was enriched. But in fact, beriberi is still widespread due to the Oriental equivalent of junk food.

Pellagra: Vitamin B3 (Niacin) Deficiency

Although described in Italy in 1735, pellagra was not recognized in the United States until the early 20th century. This disorder, like beriberi, affects many systems in the body,

though it shows most clearly in what has been called the three "D"s:

dermatitis, diarrhea, and dementia.

In 1902, a Georgian farmer complaining of weight loss, great blisters on his hands and arms, and melancholy every spring for the previous 15 years was recognized to be suffering from pellagra. Four years would elapse until it was diagnosed again, this time in an Alabama insane asylum, where the classic constellation of diarrhea, dermatitis, dementia and even death appeared in multiple inmates. Over the next five years, southern clinicians would increasingly diagnose pellagra among their poor and institutionalized populations. These people subsisted largely on a diet of corn and fat pork. The situation was most acute for those living in prisons, orphanages, and asylums. Eight states from 1907 through 1911 recorded 15,870 cases of pellagra with a 39% fatality rate. In South Carolina alone in 1912, there were 30,000 cases with 12,000 deaths. But this underestimated the problem, as only 1 in 6 people suffering from pellagra sought out a physician.

Joseph Goldberger

At that time, physicians believed that pellagra was caused by a germ of some sort, perhaps a fungus on corn or a virus spread by flies. In 1914, the US Surgeon General sent Dr. Joseph Goldberger, a physician in the Public Health Service, south to investigate the cause of pellagra. He was impressed by the monotony of the diet eaten by the poorest Southerners, especially mill workers, tenant farmers, and institutionalized persons.

Manipulating diet in experimental studies, he was able to both create and cure pellagra. Despite the denial of southern politicians that such malnutrition existed, in each of the years 1928, 1929, and 1930, the South suffered more than 200,000 cases of pellagra and 7,000 deaths. Like hookworm, this disease further weakened the southern workforce and stunted the physical and mental growth of children.

A major part of this story is that Goldberger sought for many years to

promote better nutrition, a campaign that pit him against those who wanted to spend as little money as possible: Employers, of course; but also politicians whose careers to some extent depended on the contributions of their wealthier constituents.

Goldberger's prescription of a nutritious diet was beyond the means of many Southerners, but in the 1920s, researchers found that brewer's yeast could prevent the disease. After work in the 1930s showed nicotinic acid to be the precise defect in pellagra, flour producers began to enrich both white and corn flour with the newly identified vitamin. Such foods, coupled with rising prosperity after World War II, finally eradicated pellagra in the South.

Goldberger worked tirelessly in his laboratories. here shown with his assistant and in another laboratory that was in effect more of a kitchen!

Summary

It should be noted that just because it’s a vitamin doesn't mean that it's a panacea---another word for cure-all. The National Institute for Health (NIH) has coordinated a variety of studies into the health benefits of various vitamins. In a recent news article in the Austin-American Statesman

newspaper (12/25/08, page A-13 ) a number of trials of alternative health approaches have been done by a variety of organizations. The claim by

alternative health folks that the “establishment” isn’t doing anything is clearly not true—there are many groups trying to explore plausible hypotheses. But just because there are claims it doesn’t mean they are true. For example, in two long term trials involving more than 50,000 people, Vitamin C, Vitamin E, and/or selenium supplements did NOT reduce risk of cancer of the prostate, bladder, or pancreas. And in other studies, over-the-counter vitamins were of no help in preventing stroke or cardiovasc disease. As mentioned above, certain vitamins—especially the fat-soluble ones, A and D, in high doses, accumulate in fatty tissues and may in themselves be toxic and cause "hyper-vitaminosis" diseases. It's also possible to ingest too much of certain minerals. Yet 64 % of Americans take vitamin supplements, and sales in the last twelve years have doubled. Other research: Vitamin A in the form of beta carotene, did not help and may even add to risk of cardiovascular disease. Eighteen thousand smokers or people with asbestos in their lungs had an incidence of cancer that was 28% higher among those who took beta carotene and/or Vit A. (Perhaps beta carotene curbs the body’s ability to metabolize or break down excessive Vitamin A.)

Furthermore, the NIH found through its Womans Health Study of forty thousand women over ten years that those who took Vitamin E showed no statistical benefits compared to those who didn't when it came to the incidence of heart disease, and the "anti-oxidant" porperties of Vitamin C or beta-carotene also showed no effect when it came to heart disease. Physicians in a health study again showed no benefits from Vitamin C or Vitamin E, and in another 36,000 women, Vitamin D or selenium offered no protection against breast cancer.

The emergence of the recognition of the need for a more varied diet with a wider range of vitamins and minerals was only around 80 - 110 years ago. That is to say, while the first four lectures dealt with events generally occurring between the mid-1700s through around 1870, the lecture today will address the era known as fin-de-siecle—French for “end of the century”—referring to the end of the 19th and beginning of the 20th century; and next week we’ll talk about changes that began in the mid-19th but continue well into the present time.

Anyway, vitamins emerged during my parents’ youth and still were a big thing when I was growing up. Their being so special was because they were an emerging technology. Deficiency disease was still prevalent when they were growing up. They hadn’t yet started fortifying foods—a term that means adding synthetically produced vitamins D, some B vitamins, iodine in the salt, and so forth. So I want to re-state in our parents’ honors that we may join them in appreciating these developments and allowing ourselves to appreciate by learning a bit about how these changes came about, honoring the efforts of the pioneers.

The funny thing is that many of the pioneers were right for partly the wrong reasons, or were wrong for a while before they finally came up right, and that’s another point of these stories. When I was growing up discoverers, it seemed, knew where they were going and how to get there. Only later did I discover that, say, Columbus, was largely mistaken about a number of what he thought he had discovered and it wasn’t that at all, plus his management of his team and the indigenous tribes he encountered was, let’s just say, poor.

Complicating this is that people often suffered from multiple dietary deficiencies, perhaps co-morbid with other chronic infections such as hookworm disease, malaria, and so forth. The term “co-morbid” is worth knowing, meaning simply that a person can come into the emergency room with both a broken arm and a burn.Another disorder of malnutrition came with some of the elderly patients who drifted into a tea-and-toast type diet, emphasizing easy-to-prepare foods, and as a result developing a variety of nutritional deficiency diseases. I suspect this to be happening even today!

In the last part of the first aphorism of Hippocrates, the father of medicine, I

interpret this as a call on the physician to be active in public health, and ultimately in politics. One might even wonder about the boundary with religion—there are questions about the basic question of ... but is it good for health?.. in a number of religious traditions. It’s the politics—not just the politics of getting an idea accepted within the profession, which we have talked about—but getting an idea accepted by the politicians in the service of changing the social system. A major part of this is just getting the haves in control to arrange to share a bit with the have-nots out of power, and I’m not talking about small changes, nor class warfare, whatever that means—I may do a series on the realities of class in modern society, and how folks try to pretend that it’s not there---- but the truth is that in many parts of the world, folks are sick and dying and starving to death. So can physicians rightly try to make externals cooperate? This is the boundary of public health that well weave in both today and next time.

References

Frankenburg, Frances R. (2009). Vitamin discoverieds and disasters: History, science & controversies. Santa Barbara, CA: Praeger / ABC-CLIO.

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