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Friday, August 26, 2011

More About Thiamine

Some of the most harrowing stories of nutrient deficiencies come from the 18th and 19th century British Navy.  Perhaps because the officers on the long voyages had nothing better to do than document the slow, desperate and horrific progression?  Recently there was a PBS special on the Erebus, a ship that left Britain in 1845 under Captain Franklin to look for the Northwest Passage.  This voyage occurred during a century of Arctic and Antarctic exploration that included Shackleton's famous doomed voyage (the memoir, South, is well worth reading).  Those poor sailors on the Erebus, though.  See, just before their planned expedition, the process of food canning was, um, perfected. The Admiralty was thrilled - now they could send the ships around the world and not worry about local conditions or foraging for food.  They would include plenty of canned fruits rich in vitamin C so that most horrible sailor's disease, scurvy, would not affect the crew.  Scurvy is a horrible way to die - your connective tissue degrades and you spend a great deal of time in terrible pain as you slowly bleed to death internally.  Go civilization!  Let's conquer the Arctic!

Well, the ship sailed off with Franklin and a crew of 128 and was nearly never heard from again.  There were a few accounts of sightings, and rumors of mutiny and cannibalism reached Britain.  Turns out that the cans were soldered with lead, and the water supply may also have been contaminated.  And it so happens that the vitamin C in canned foods only lasts about a year, so after the ship bogged down in ice for several seasons, the sailors who weren't weakened, crazed, and killed by lead poisoning succumbed to hypothermia and scurvy.  The luckier sailors on the Shackleton expedition brought some guns along and hunted and fished for the years they were stranded after their ship was crushed in the ice (one can't help but notice that all those cute sled dogs present at the beginning of the voyage are gone by the end).  And they got through okay - Shackleton didn't lose a single man.  The crew of the Erebus may be some of the first victims of modern processed food.

While thiamine deficiency was described as "sailor's asthma" in the Navy, this disease was better known in Japan as "Kakke" and had been described as early as year 808 (1).  In the early 20th century, 30 per 100 Japanese died of the disease.  Once thiamine was discovered, mortality dropped to 0.5 per 100 Japanese.  The major symptoms were poor reflexes, swelling, low diastolic blood pressure, and tender calf muscles.  Cardiovascular symptoms include a weakening and enlargement of the heart, called "cardiomyopathy" which will eventually result in heart failure (and lung symptoms as the circulation backs up in the lungs - thus "sailor's asthma.") Peak deaths, both in adults and infants, occurred between August and September, even more so when humidity was high.

Before thiamine was isolated, it became obvious (from voyages of the Japanese Navy and from birds fed a strict diet of white rice) that polished rice was the major contributor to beriberi, and that adding red beans, dried meat, rice bran, or barley to sailor's rations prevented the disease.  It is the original "empty calorie" disease.  Thiamine, first isolated in 1926, is now known to have some plentiful sources:  meat, wheat germ, liver, organ meats, poultry, eggs, fish, beans, nuts, and whole grains.  Cooking and processing depletes the vitamin, but you don't need much - just 0.5mg per 1000 calories consumed.  Polyphenols in coffee and tea can inactivate thiamine, so stick to red wine (just kidding - alcohol interferes with the absorption of thiamine, remember?)  

Like most vitamins, thiamine is taken up into the body and then immediately modified into a number of derivatives.  The most famous is thiamine diphosphate (also known as TPP) - this thiamine is the one that plays a part in a bunch of energetic reactions in glucose metabolism.  If you want your citric acid cycle to run (and believe me, you do), you need thiamine diphosphate.  Bodybuilders and BCAA chuggers take note - you also need TPP to  decarboxylate the keto acids derived from the branched chain amino acids.  You also need TPP in the pentose shunt, which is an important extra-energy and detox pathway.  Deficiency of TPP is what eventually shows up as Wernike's encephalopathy and Korsakoff's psychosis among the present day severe alcoholic set.

What is interesting about these old-fashioned deficiency syndromes is that thiamine deficiency today (most commonly seen as Wernike's) isn't the same thing as beriberi.  Just as strict vitamin D deficiency isn't quite the same as rickets.  With beriberi, there is a clear relationship between the classic symptoms and the amount of carbohydrates in the diet.  With Wernike's we know we can bring it on with a bolus of D5W after someone has been living on booze, but Wernike's is missing many of the essential features of beriberi.  The modern form is almost entirely confined to the central nervous system.

(It is an assumption nowadays that we have conquered the major deficiency syndromes with science.  And, indeed, rickets is rare, beriberi is unknown in the Western world, and anyone ever see a case of pellagra?  But my suspicion is that many of our modern diseases are primarily caused by or exacerbated by micronutrient deficiencies.  We shouldn't be so complacent.  *off soapbox*)

Thiamine, with its key role in central nervous system energy production, can give us clues as to the pathology of syndromes such as Alzheimer's Dementia.  Folks with AD have normal thiamine levels, but low levels of the metabolically active TPP, suggesting problems with energy regulation.  Giving people with AD extra thiamine can sometimes help the symptoms.  

In Japan, there has been a long historical interest in thiamine, and they have come up with a number of synthetic thiamine derivatives.  One of them, a disulfide derivative called sulbutiamine, crosses the blood brain barrier more readily than regular thiamine.  I don't know much about it, but given the impact of energetics on disorders such as Parkinson's Disease and Alzheimer's, it seems an obvious candidate for further research.

In the mean time, eat your meat, especially if you are a big fan of white rice (though white rice in the US I believe is fortified with thiamine), or alcohol.

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