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- - - GOLDBERGER ON PELLAGRA

Friday, 29th of March 2013

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• GOLDBERGER ON PELLAGRA / FAO GUIDELINES  ON PELLAGRA
    

 The proof that pellagra is a nutritional disease came from South  Carolina studies published by Dr. Joseph Goldberger in 1915. Whether  the experiments he performed on himself and his assistant would pass a  bioethics committee today is an open question.
 
 The following is from the homepage of the NIH. After the NIH text, the  FAO guidelines on pellagra.
 
 http://history.nih.gov/exhibits/Goldberger/index.html 
 
 
 Dr. Joseph Goldberger & the War on Pellagra
 
 Pellagra no longer stalks the nation as it once did. But during the  early part of the 20th century, pellagra, a disease that results from  a diet deficient in niacin, killed many poor Southerners. Dr. Joseph  Goldberger, a physician in the U.S. government's Hygienic Laboratory,  the predecessor of the National Institutes of Health, discovered the
 cause of pellagra and stepped on a number of medical toes when his   research experiments showed that diet and not germs (the currently  held medical theory) caused the disease. He also stepped on Southern  pride when he linked the poverty of Southern sharecroppers, tenant
 farmers, and mill workers to the deficient diet that caused pellagra.

 
 Joseph Goldberger's theory on pellagra contradicted commonly-held  medical opinions. The work of Italian investigators as well as  Goldberger's own observations in mental hospitals, orphanages, and  cotton mill towns, convinced him that germs did not cause the disease.
 In such institutions, inmates contracted the disease, but staff never  did. Goldberger knew from his years of experience working on  infectious diseases that germs did not distinguish between inmates and  employees. Lombroso had speculated that spoiled maize caused pellagra.
 
 Goldberger found no evidence for that hypothesis, but diet certainly  seemed the crucial factor. Shipments of food that Goldberger had  requested from Washington were provided to children in two Mississippi  orphanages and to inmates at the Georgia State Asylum. Results were  dramatic; those fed a diet of fresh meat, milk and vegetables instead  of a com-based diet recovered from pellagra. Those without the disease  who ate the new diet did not contract pellagra.
 
 Critics, many unable to part from the germ theory of pellagra, raised  doubts. Goldberger hoped to squelch those reservations by  demonstrating the existence of a particular substance that when  removed from the diet of healthy individuals resulted in pellagra.
 With the cooperation of Mississippi's progressive governor, Earl  Brewer, Goldberger experimented on eleven healthy volunteer prisoners  at the Rankin State Prison Farm in 1915. Offered pardons in return for  their participation, the volunteers ate a corn-based diet. Six of the  eleven showed pellagra rashes after five months.
 
 Expert dermatologists made the actual diagnosis of pellagra to avoid  the appearance of a conflict of interest on Goldberger's part. 
 Although many scientific colleagues sang Goldberger's praises, even  mentioning a Nobel nomination, others still doubted. In the pages of  the Journal of the American Medical Association, critic W.J. MacNeal  challenged the results. One Birmingham physician referred to the  experiment as "half-baked." Still others thought the whole experiment  a fraud.
 
 Angry and frustrated, Goldberger would not give up trying to persuade  his critics that pellagra was a dietary disorder, not an infectious  disease. He hoped that one final dramatic experiment would convince  his critics. On April 26, 1916 he injected five cubic centimeters of a  pellagrin's blood into the arm of his assistant, Dr. George Wheeler.
 Wheeler shot six centimeters of such blood into Goldberger. Then they  swabbed out the secretions of a pellagrin's nose and throat and rubbed  them into their own noses and throats. They swallowed capsules  containing scabs of pellagrins' rashes. Others joined what Goldberger  called his "filth parties," including Mary Goldberger. None of the  volunteers got pellagra. Despite Goldberger's heroic efforts, a few  physicians remained staunch opponents of the dietary theory of  pellagra.
 
 Goldberger vs. The South
 
 If poor diet resulting from poverty among Southern tenant farmers and  mill workers was the root cause of pellagra, then the only real cure  was social reform, especially changes in the land tenure system. A  dramatic drop in cotton prices in 1920 and the attendant decrease in
 the income of many Southerners occasioned a spike in the number of  reported pellagra cases. Goldberger publicly predicted dire public  health consequences for 1921 when there might be as many as 100,000  pellagra cases including 10,000 deaths and even worse for 1922.
 
 
 Newspaper headlines warning of famine and plague in the South caught  the eye of President Warren G. Harding, who asked Surgeon General Hugh  Cumming for a report and was supportive of PHS appeals for an  increased budget for hospitalization and supplies. The Public Health  Service called upon Southerners to provide local relief for the poor.
 However, the response of many in the South was the opposite of  grateful and magnanimous. Enraged Southerners, led by South Carolina  Congressman Jimmy Byrnes, denounced the negative characterization of  their region and feared that it would discourage economic investment  and tourism in the South. They believed that Southern pride and  Southern prosperity were on the line.
 
 Goldberger proved correct. There was a dramatic increase in pellagra  and in the number of deaths, although not quite as many as he had  predicted. The land reform that Goldberger believed necessary to  eliminate pellagra was accomplished not by scientific reasoning but by  the invasion of boll weevils. The insect destroyed cotton fields and  forced Southerners to diversify their crops. By growing more food  crops, Southerners improved their diets and suffered less from  pellagra.
 
 
 The Great Mississippi Flood
 
 During the 1920s, Goldberger continued research to identify what he  called the "pellagra preventive factor." He learned that small amount  of dried brewer's yeast prevented the disease as effectively and more  cheaply than fresh, lean meat, milk, and vegetables. He also began  laboratory experiments on dogs after learning that black tongue  disease was the canine equivalent of pellagra. When the Mississippi  River overflowed its banks in 1927, Goldberger returned to the field  with PHS statistician Edgar Sydenstricker. Together they traveled the  Mississippi valley collecting statistical data on every aspect of
 Southern life for their epidemiological studies while delivering  jeremiads against the system that left the poor too destitute to eat a  healthy diet. The message was unwelcome and unheeded. 
 
 From the FAO Guidelines on Pellagra,
 http://www.fao.org/DOCREP/W0073e/w0073e05.htm#P4008_468640
 
 Pellagra
 
 Causes and epidemiology
 
 Pellagra, caused mainly by a deficiency of dietary niacin, is  generally associated with a maize diet in the Americas, just as  beriberi is associated with a rice diet in East Asia.
 
 As mentioned in the discussion of niacin in Chapter 11, a number of  factors have at different times been suggested as the cause of  pellagra. Each theory seemed, when first expounded, to oppose another.
 Three of the principal theories appear to have an element of truth.
 Pellagra was first thought to be caused by a toxin in maize, then by a  protein deficiency and finally by a lack of niacin in the diet. 
 
 It has now been found that maize contains more niacin than some other  cereal foods, but it is believed that the niacin in maize is in a  bound form. In Mexico, Guatemala and elsewhere where maize has  traditionally been treated with alkalis such as lime water to make
 tortillas and other foods, consumers have been protected from  pellagra. It is possible that lime treatment followed by cooking makes  the niacin more available, or perhaps it improves amino acid balance.
 The human body can convert the amino acid tryptophan into niacin; thus  a high-protein diet, if the protein contains good quantities of  tryptophan, will prevent pellagra. Nonetheless, niacin is still the  most important factor in pellagra, and any programme to prevent the
 disease should aim at providing adequate niacin in the diet.
 Similarly, all cases of pellagra should receive niacin  therapeutically.
 
 
 Pellagra used to be a very prevalent disease in the southern United States, particularly among poor sharecroppers in the early part of the  twentieth century. The disease, unknown in Europe in earlier times,  became prevalent in the eighteenth and nineteenth centuries as maize
 for the first time began to be widely eaten in Italy, Portugal, Spain  and parts of eastern Europe. In the twentieth century pellagra has  been common in Egypt and parts of southern and eastern Africa, and  sporadic cases have been reported in India. In each of these areas the
 disease was associated with maize becoming the staple diet of poor  people who could afford very little else to supplement the diet.
 
 The highest prevalence in recent times has probably been in South  Africa, where conditions for some agricultural and industrial workers  until 1994 were not unlike those in the southern United States between  1900 and 1920. A report from South Africa suggested that 50 percent of  patients seen at a clinic in the Transvaal had some evidence of  pellagra, and that the majority of adults admitted to the mental  hospital in Pretoria had the disease.
 
 Pellagra regrettably has also been widely reported in refugee camps  and in famine situations where maize has been the relief food and  relief agencies have given too little attention to providing a  balanced diet or adequate micronutrient intakes. An outbreak of  pellagra occurred during a drought in central Tanzania in the 1960s  when the affected people were consuming mainly donated maize from the  United States. The pellagra was quickly controlled using niacin  supplements.
 
 Clinical manifestations
 
 Persons suffering from pellagra usually appear poorly nourished. They  are often rather weak and underweight. The disease is characterized by  "the three Ds": dermatitis, diarrhoea and dementia (Figure 10). Mild  sensory and motor changes such as diminished sensitivity to gentle  touch, some muscular weakness and tremor all occur. A wide variety of  other signs have been described. Paralysis, however, is rare.  Untreated cases of pellagra may die of the disease.
 
 Dermatitis
 
 The disease is most often diagnosed from the appearance of the skin,  which has characteristic lesions. The lesions occur on areas of the  skin exposed to sunlight, such as the face, the back of the hands, the  neck, the forearms and exposed portions of the leg. This pellagrous  dermatitis begins with a deepening of the pigmentation. The  hyperpigmented areas lose the oily sheen of healthy skin and become  dry, scaly and eventually cracked. There is usually a definite line of  demarcation between these lesions and the healthy skin, and this line  can be felt, for the affected area is rough to the touch. The skin  condition may remain static, heal or progress. If it progresses,  desquamation commonly occurs; there may be cracking and fissuring, or  occasionally the skin may blister. The blisters contain a colourless
 exudate. Areas that have shed a layer of skin are sometimes shiny,  thin and rather depigmented. All these skin lesions are usually more  or less symmetrical.
 
 In white subjects the skin lesions initially look like the erythema of  sunburn. In both black and white patients, the lesions of pellagra  produce burning sensations and pain when exposed to the direct rays of  the sun, just as sunburn does in a person with pale skin. The lesions  may also correspond with a hole or holes in a frequently worn garment  which allowed the sunlight to reach the skin. For example, the classic  Casal's necklace around the neck and upper chest results from the sun  playing on this part of the body in a subject wearing an open-necked  shirt.

 
 The tongue and other parts of the mouth are often sore, red, smooth  and raw-looking. Angular stomatitis and cheilosis, usually associated  with riboflavin deficiency, are frequently observed.
 
 Diarrhoea
 
 Bouts of abdominal pain, diarrhoea and other digestive upsets are  frequently associated with pellagra. It is believed that changes  similar to those that occur in and around the mouth are present in  various other parts of the alimentary tract, and these may be the  cause of abdominal discomfort and intestinal burning. Few if any of  these symptoms and signs are specific to pellagra, but if they  accompany skin changes or mental symptoms or respond to niacin, a  diagnosis of pellagra is supported.
 
 Dementia
 
 Involvement of the nervous system is manifested by extremely variable  symptoms and signs. The most common are irritability, loss of memory,  anxiety and insomnia. These symptoms may lead to dementia, and it is  not uncommon in practice for persons with dementia resulting from  pellagra to be admitted to mental institutions. All cases of insanity,  especially where maize is the staple food and where pellagra occurs,  should therefore be examined for other signs of pellagra.
 
 Diagnosis and laboratory tests
 
 The skin lesions are usually characteristic in appearance. Lesions  that are symmetrical and on surfaces of the body exposed to sunlight  substantiate the diagnosis. The symptoms and signs involving the  alimentary canal and nervous system are not often specific. The  dietary history, the presence of skin changes, the appearance of the  mouth and above all a good response to niacin are indicative. In  children the stunted growth or wasting of protein-energy malnutrition  may also be present.
 
 Assessment of urinary excretion of N-methylnicotinamide is used both  in nutritional surveys and in evaluation of individual patients for  niacin deficiency. In six-hour urine collections, nicotinamide levels  between 0.2 and 0.5 mg are considered low, and a level below 0.2 mg  indicates niacin deficiency. In random urine specimens, deficiency is  suggested by less than 0.5 mg nicotinamide per gram of creatinine.
 Urinary levels are more useful for providing information on recent  consumption of niacin and tryptophan, however, than for the diagnosis  of pellagra. Nevertheless, normal amounts of N-methylnicotinamide in  urine may help rule out pellagra as the diagnosis.
 
 Treatment
 
 The following treatment is recommended for pellagra.
 
 · Admission to hospital and rest in bed are desirable for serious  cases. Milder cases may be treated as out-patients.
 
 · The patient should be given 50 mg of niacin (nicotinic acid,  nicotinamide) three times a day by mouth.  · The diet should contain at least 10 µg per day of good protein (if  possible, meat, fish, milk or eggs; if not, groundnuts, beans or other  legumes) and should be high in energy (3 000 to 3 500 kcal per day).
 
 · Because the patient may also have a deficiency of other B vitamin  components, a vitamin B complex preparation or a yeast product should  be prescribed.
 
 · Sedation for a few days is recommended. Those with mental  disturbances benefit greatly from any of a number of tranquillizers,  for example, valium. The sedative should be given orally, but if the  patient is uncooperative more potent tranquillizers may be needed by  injection.
 
 Pellagra is often a very gratifying disease to treat. Violent, almost  uncontrollable mental patients can become normal, rational, peaceful  human beings within a few days of taking a few tablets of  nicotinamide. In persons with severe skin lesions, a sore mouth and  severe diarrhoea with frequent watery stools, dramatic improvements  occur within 48 hours. The skin redness and pain on exposure to  sunlight improves; pain in the mouth abates and eating becomes a  pleasure for the patient; and most gratifying for the patient, the  intractable diarrhoea disappears.

 Prevention
 
 The following steps can help in the prevention of pellagra.
 
 · Diversity in the diet is important. Reliance on maize as the sole  staple foodstuff should be discouraged, and the consumption of other  cereals in place of part of the maize should be encouraged. This is  less necessary in those parts of the Americas where maize is treated  with lime.
 
 · Production and consumption of foods known to prevent pellagra, i.e.  those rich in niacin, such as groundnuts, and those rich in  tryptophan, such as eggs, milk, lean meat and fish, should be  increased.
 
 · Legislation or other inducement should be put in place to ensure the  enrichment of milled maize meal with niacin.
 
 · Niacin tablets should be administered as a prophylaxis in prisons  and institutions in areas where pellagra is endemic, and to refugees  and in famine relief.
 
 · Nutrition education should be provided to teach people what foods  can prevent the disease.
  
 An important lesson to be learned from past experience in the southern  United States and current experience in South Africa is that pellagra  will be controlled if the conditions for poor agricultural and  industrial workers are improved. In the United States the end of  slavery, the reduction of sharecropping on southern farms and  improvements in wages, working conditions and food supplies had more  impact in reducing pellagra than did fortification or medicinal  nicotinamide supplements. Recent political changes in South Africa are  likely to change and improve the working conditions and diets of poor  Bantu in that country and to reduce the prevalence of pellagra there.