Vitamin B1

Supplemental thiamine (B1) produces no noticeable acute effects in individuals who are not deficient. In those with deficiency, however, repletion can produce a gradual improvement in mental clarity, energy levels, and cognitive function over days to weeks. The fog lifts. Concentration improves. Fatigue recedes. The experience is one of restoration rather than enhancement, a return to normal function rather than a boost beyond it.

Thiamine pyrophosphate (TPP) is the essential coenzyme for three critical enzyme complexes: pyruvate dehydrogenase complex (linking glycolysis to the citric acid cycle), alpha-ketoglutarate dehydrogenase complex (a rate-limiting step of the citric acid cycle), and transketolase (pentose phosphate pathway, producing NADPH for antioxidant defense and ribose for nucleotide synthesis).

In the brain, TPP-dependent enzymes are essential for aerobic glucose metabolism, which supplies ~95% of the brain's energy. Thiamine deficiency leads to impaired oxidative metabolism, lactic acidosis, oxidative stress, excitotoxicity, inflammation, and selective neuronal death particularly in metabolically active regions (mammillary bodies, thalamus, periaqueductal gray, superior cerebellar vermis).

Beyond its coenzyme role, thiamine modulates ion channels (including chloride channels at the neuromuscular junction), may function as a neurotransmitter or neuromodulator through release from nerve terminals, and maintains myelin integrity. Benfotiamine and sulbutiamine are lipid-soluble thiamine derivatives with enhanced bioavailability and CNS penetration.

• Further information: Vitamin §History Thiamine was the first of the water-soluble vitamins to be isolated. The earliest observations in humans and in chickens had shown that diets of primarily polished white rice caused beriberi, but did not attribute it to the absence of a previously unknown essential nutrient.

In 1884, Takaki Kanehiro, a surgeon general in the Imperial Japanese Navy, rejected the previous germ theory for beriberi and suggested instead that the disease was due to insufficiencies in the diet. Switching diets on a navy ship, he discovered that replacing a diet of white rice only with one also containing barley, meat, milk, bread, and vegetables, nearly eliminated beriberi on a nine-month sea voyage. However, Takaki had added many foods to the successful diet and he incorrectly attributed the benefit to increased protein intake, as vitamins were unknown at the time. The Navy was not convinced of the need for such an expensive program of dietary improvement, and many men continued to die of beriberi, even during the Russo-Japanese War of 1904–05. Not until 1905, after the anti-beriberi factor had been discovered in rice bran (removed by polishing into white rice) and in barley bran, was Takaki's experiment rewarded. He was made a baron in the Japanese peerage system, after which he was affectionately called "Barley Baron".

The specific connection to grain was made in 1897 by Christiaan Eijkman, a military doctor in the Dutch East Indies, who discovered that fowl fed on a diet of cooked, polished rice developed paralysis that could be reversed by discontinuing rice polishing. He attributed beriberi to the high levels of starch in rice being toxic. He believed that the toxicity was countered in a compound present in the rice polishings. An associate, Gerrit Grijns, correctly interpreted the connection between excessive consumption of polished rice and beriberi in 1901: He concluded that rice contains an essential nutrient in the outer layers of the grain that is removed by polishing. Eijkman was eventually awarded the Nobel Prize in Physiology and Medicine in 1929, because his observations led to the discovery of vitamins.

In 1910, a Japanese agricultural chemist of Tokyo Imperial University, Umetaro Suzuki, isolated a water-soluble thiamine compound from rice bran, which he named aberic acid. (He later renamed it Orizanin.) He described the compound as not only an anti-beriberi factor, but also as being essential to human nutrition; however, this finding failed to gain publicity outside of Japan, because a claim that the compound was a new finding was omitted in translation of his publication from Japanese to German. In 1911 a Polish biochemist Casimir Funk isolated the antineuritic substance from rice bran (the modern thiamine) that he called a "vitamine" (on account of its containing an amino group). However, Funk did not completely characterize its chemical structure. Dutch chemists, Barend Coenraad Petrus Jansen and his closest collaborator Willem Frederik Donath, went on to isolate and crystallize the active agent in 1926, whose structure was determined by Robert Runnels Williams, in 1934. Thiamine was named by the Williams team as a portmanteau of "thio" (meaning sulfur-containing) and "vitamin". The term "vitamin" coming indirectly, by way of Funk, from the amine group of thiamine itself (although by this time, vitamins were known to not always be amines, for example, vitamin C). Thiamine was also synthesized by the Williams group in 1936.

Sir Rudolph Peters, in Oxford, used pigeons to understand how thiamine deficiency results in the pathological-physiological symptoms of beriberi. Pigeons fed exclusively on polished rice developed opisthotonos, a condition characterized by head retraction. If not treated, the animals died after a few days. Administration of thiamine after opisthotonos was observed led to a complete cure within 30 minutes. As no morphological modifications were seen in the brain of the pigeons before and after treatment with thiamine, Peters introduced the concept of a biochemical-induced injury. In 1937, Lohmann and Schuster showed that the diphosphorylated thiamine derivative, TPP, was a cofactor required for the oxidative decarboxylation of pyruvate.

• Some contributors to the discovery of thiamine

Takaki Kanehiro

Christiaan Eijkman

Gerrit Grijns

Umetaro Suzuki

Casimir Funk

Rudolph Peters