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CSU 29/2009: GOLDBERGER ON PELLAGRA / FAO GUIDELINES ON PELLAGRA

Friday, 15th of May 2009

 CSU 29/2009: 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.