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Niacin and Pellagra

Niacin was discovered in 1837 by the Austrian chemist Hugo Weidel, who synthesised it by oxidising nicotine with nitric acid. He called the resulting compound "nicotinic acid". It was already known that a compound could be created by oxidising nicotine, but no-one had managed to create enough of the resulting acid to be able to figure out its properties.

Even though Niacin was discovered in 1837, it wasn't until 100 years later that it was recognised as a nutrient. The story for that leads through an epidemic in southern USA.

Pellegra

At the beginning of the twentieth century, in the southern US states, a large number of people started dying of a disease called "Black Tongue", "Zeism", or "Mal De La Rosa". We now call it pellegra. In 1914, it had escalated to the point that the United States senate declared it an epidemic and started working on figuring it out [1].

Symptoms included diarrhoea, mental confusion, loss of weight, weakness, irritation in the mouth and stomach linings, and lesions of the skin. Skin, especially that which was exposed to the sun, would become dark, thick, and scaly. The disease was sometimes misdiagnosed as leprosy. Sometimes the mental confusion would lead to depression, irrational violence, or lethargy.

Pellagra symptoms in the hands

Two our of every three people that exhibited signs of pellegra died of it.

It was believed, based on centuries of the disease in other countries, that pellegra was caused by diseased or spoiled corn.

The favoured meal of the day was corn-bread and mollasses. They were cheap and abundant. It was not easy then to get a varied diet.

North Carolina, for example, had a quarter of a million farms in the early 20th century, most of which were manned by low-waged people living on tenant-farms. The cash-crops at the time were cotton and tobacco. Food crops common at the time were wheat, oats, corn, rice, sweet potatoes [1]. If you wanted to eat, it would be made from those staples.

It was recognised by most doctors that pellegra was associated strongly with poverty and with diet.

However, the idea that people were dying because they were poor was politically distasteful, causing some politicians to utterly deny it. In Georgia, a senator was sent a wire stating "When this part of Georgia suffers from famine, the rest of the world will be dead!". Another group sent a letter to president Harding, said "Famine does not exist anywhere in the South, and we fail to find a general increase in pellagra". When people get stubborn, you can't show them what's right in front of them.

An alternative theory started to gain ground, that pellegra was an infectious disease, and therefore not related to poverty or diet. This theory had no evidence backing it, and existed purely because its proponents could not bear the shame that perhaps the USA was not feeding its workers properly.

Tests on prison inmates, orphans, and the insane

In 1914, Dr Joseph G Goldberger was assigned by the surgeon general to work on the problem, starting it by doing a three-week tour of a hospital, orphanages, and an asylum for the insane, which helped him confirm that Pellegra is not a communicable disease. Not one staff member at any of the institutions caught pellegra from the patients or inmates.

With an insight, Goldbeger noted the monotony of the meals that were provided at these institutions. He noted that even though patients and staff ate from the same menus, the staff usually ate first, taking the choicest meals and leaving the worst, and the staffcould supplement their meals with food bought elsewhere.

At the orphanages, pellegra did not occur in children under 6 or over 12. Goldbeger noted that the infants had meals supplemented with extra milk, and the older children were given work to do and then rewarded with better food.

The link was obvious, once pointed out. Goldbeger set out to prove it.

He set up an experiment using federal money, where some of the orphanages and some of the asylum inmates were fed with more varied diets. Everyone that was given the new varied diets recovered from their pellegra, and did not relapse.

He reported his success to the Public Health Service, but unfortunately had to stop the program when he ran out of funding. As soon as he did, the old diet was resumed in all places, and the patients started getting pellegra again.

The next year, in 1915, he presented his results at the Association for the Study of Pellegra. At the meetings, he was vilified by proponents of the infectious disease theory, and his cnclusion that a more varied diet was the solution, was ridiculed.

To prove his case, Dr Goldbeger decided he would cause pellegra. If he could selectively decide who got pellegra, and who didn't, and his decisions came true, that would be proof enough.

He got the help of a prison in Mississippi which had never had a case of pellegra, thus eliminating the "infectious" part of the argument. Eleven volunteer prisoners were housed separately from the rest and fed a strict diet of biscuits, gravy, grits (porridge made from corn), cornbread, rice, syrup (sugar), collards, and yams.

The experiment begane in February, and was stopped at the end of October. Pellegra was present in more than half of them. Goldberger was accused of torture. Even doctors who had applauded his efforts before were now criticising him. Skeptics were still not convinced pellegra was not infectious. You can't pleases everyone.

In another attempt to prove that pellegra was not infectious, Dr Goldbeger ran some "filth parties", where he injected himself, associates, and his wife with blood from infected pellegra patients, and ate dough balls which contained skin scales, urine, and faeces from pellegra sufferers. No-one contracted pellegra. There was some diarrhoeah and nausea, but that's understandable. The skeptics were again not convinced...

In the end, he stopped trying to convince people that refused to be convinced, and instead devoted his time to trying to find what was missing from the diets, based on the research he had done so far. He called it "PPF" (pellegra preventative factor). Others called it "vitamin G" (for Goldbeger).

His diet suggestions were noted, and saved many thousands of people, even before niacin was eventually isolated.

Goldbeger came across an animal insight. He became aware of a paper on malnutrition where doctors stufying malnutrition at Yale had fed dogs on a restricted diet of boiled peas, cracker meal, and cottonseed oil. The dogs developed symptoms that looked very much like pellegra, with sores and haemorrhages in the mouth leading it to have a blackened tongue.

Dogs in the south, around the area where pellegra was most active, had been noted to sometimes have a "canine plague" which the infectious theory proponents thought helped prove the idea that the disease was being carried from person to person, sometimes via dog.

One side effect of the ulcers in the mouth was that the dogs found it difficult to swallow. To help with this, owners sometimes used yeast as a salve, which helped cure the issues.

Goldbeger and his team realised that the yeast must contain the PPF.

In 1927, the Mississippi flooded, and Goldbeger was able to arrange for a large amount of the yeast to be shipped into places along the Mississippi that were afflicted. That year, the expected outbreaks of pellegra were dramatically reduced. Next year, however, the floods did not return, so he could not allocate the money again, and pellegra returned.

By now, it was well known (among those that would listen) that the cure was a varied diet, and the cause itself was a matter of narrowing down the possibilities.

The last thing that Goldbeger worked on before his death in 1929 was on trying to extract PPF from liver, which was found to be very effective in curing pellegra in both dogs and humans.

It wasn't until 1937, though, that the factor was eventually identified, and found by the biochemist Conrad Elvehjem, who had carried on the search.

PPF, the pellegra preventative factor, turned out to be nicotinic acid, now called niacin, which had been discovered 100 years before hand, but no use had been discovered for it.

Uses

It is now known that niacin treats pellegra, and can also be used to treat high blood cholesterol.

Very high doses can cause liver damage, but the damage will usually revert when if the level of niacin is brought down to the RDA. Overdosing at a 1-6g level can have a side-effect of lowering cholesterol, though, and this is used in treatment for hypercholesterolemia.

The recommended daily amounts for niacin are 16mg for males, and 14mg for females. 35mg will give you a "niacin flush", where the face or upper body turns red and feels like it is burning.