The confusion was due to the fact that riboflavin (B2) deficiency causes stomatitis symptoms similar to those seen in pellagra, but without the widespread peripheral skin lesions. For this reason, early in the history of identifying riboflavin deficiency in humans the condition was sometimes called "pellagra sine pellagra" (pellagra without pellagra).In 1935, Paul Gyorgy, in collaboration with chemist Richard Kuhn and physician T. Wagner-Jauregg, reported that rats kept on a B2-free diet were unable to gain weight. Isolation of B2 from yeast revealed the presence of a bright yellow-green fluorescent product that restored normal growth when fed to rats. The growth restored was directly proportional to the intensity of the fluorescence. This observation enabled the researchers to develop a rapid chemical bioassay in 1933, and then isolate the factor from egg white, calling it ovoflavin. The same group then isolated the a similar preparation from whey and called it lactoflavin. In 1934, Kuhns group identified the chemical structure of these flavins as identical, settled on "riboflavin" as a name, and were also able to synthesize the vitamin.Circa 1937, riboflavin was also referred to as "Vitamin G". In 1938, Richard Kuhn was awarded the Nobel Prize in Chemistry for his work on vitamins, which had included B2 and B6. In 1939, it was confirmed that riboflavin is essential for human health through a clinical trial conducted by William H. Sebrell and Roy E. Butler. Women fed a diet low in riboflavin developed stomatitis and other signs of deficiency, which were reversed when treated with synthetic riboflavin.
Adverse effects
The most common adverse effects of short-term use include headache (reported by 7% of people in clinical trials), drowsiness (2%), dizziness (1%), and diarrhea (1%); the most common side effects of long-term use included
drowsiness (8%),
dizziness (5%),
allergy (4%),
sinusitis (4%),
back pain (3%),
diarrhea (3%),
drugged feeling (3%),
dry mouth (3%),
lethargy (3%),
sore throat (3%),
abdominal pain (2%),
constipation (2%),
heart palpitations (2%),
lightheadedness (2%),
rash (2%),
abnormal dreams (1%),
amnesia (1%),
chest pain (1%),
depression (1%),
flu-like symptoms (1%),
and
sleep disorder (1%).Zolpidem increases risk of depression, falls and bone fracture, poor driving, suppressed respiration, and has been associated with an increased risk of death. Upper and lower respiratory infections are also common (experienced by between 1 and 10% of people).Residual hangover effects, such as sleepiness and impaired psychomotor and cognitive function, may persist into the day following nighttime administration. Such effects may impair the ability of users to drive safely and increase risks of falls and hip fractures. Around 3% of people taking zolpidem are likely to break a bone as a result of a fall due to impaired coordination caused by the drug.Some users have reported unexplained sleepwalking while using zolpidem, as well as sleep driving, night eating syndrome while asleep, and performing other daily tasks while sleeping. Research by Australias National Prescribing Service found these events occur mostly after the first dose taken, or within a few days of starting therapy. In February 2008, the Australian Therapeutic Goods Administration attached a boxed warning concerning this adverse effect.