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.

9 comments:

  1. Here is a forum post with cautions about sulbutiamine, but I am not sure what to think because it is too complicated:
    http://www.drugs-forum.com/forum/showthread.php?t=101487

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  2. Geez, it really took those hairless apes a long time to learn how to keep from dying. I'm glad our ancestors (and peers, it seems) made the sacrifice. Go homo sapiens!

    No doubt in my mind that most people need more micronutrients. Heck, without little bits of vitamin c left in French fries we would probably see more scurvy.

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  3. It seems that thiamine can boost cognition in others, too, than the demented: http://www.springerlink.com/content/xhvrt66252cfy202/
    (In this study, 50 mg).

    This is greater, I think, than any possible dietary quantity (if not, I wish to know!), but perhaps less would be enough to yield the same effect.

    By the way, Dr. Deans, long-time lurker here -- ace blog.

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  4. Emily I am very curious: why Kakke gave 'tender calf muscle'? What it the link? Why just the calves? (You guessed...I have cronic tender calves).

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  5. should it be assumed that if someone doesn't consume any "empty calories" (pure carbs like sugar, white rice) or any alcohol (just can't stand it) they need much less thiamine or any other 'nutrient' (be it amino or fatty acid), without fear of getting scurvy or whatever, i.e. "less is more"?

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  6. Stabby - as you know, the agricultural human anthropologic record has lots of evidence of malnutrition of various sorts (particularly iron deficiency, as that has clear skeletal findings). The paleolithic record - not so much, with better bone growth, etc. Iodine deficiency can apparently be found in mountainous regions.

    Strake - 50mg is about 35X the RDA and quite difficult to get in the diet. I haven't seen a downside to taking too much thiamine, but that doesn't mean there isn't one. Thanks :)

    Thalin - I think it is a combination of edema and peripheral neuropathy http://www.merckmanuals.com/professional/sec01/ch004/ch004f.html (swelling plus nerve damage that starts in the hands and feet and moves inward to the spinal cord) Beriberi is extraordinarily rare in the US, basically confined to breastfed infants of thiamine deficient mothers and those with genetic problems processing thiamine.

    Goodwinnihon - yes, your thiamine needs would be lower, but getting more doesn't seem to have a downside.

    All - I didn't put this next bit in the blog, as I didn't feel there was much support (ie this is rampant speculation) - combine lots of processed food and make it high carb - sure, modern grains are supplemented but maybe a subclinical (much milder) modern version of beriberi is mild autonomic insufficiency and inattention - these symptoms could look a bit like the hypoglycemia symptoms with poor impulse control and behavioral problems. Maybe some of us have inefficient thiamine phosphorylating machinery and we need a bit more thiamine than we might think to make the active versions in the body, or to get enough into the brain. Maybe we'd be fine if we didn't eat tons of sugar and processed food… the paper I was reading made it sound as if these questions have not been well investigated, and it is an intriguing theory.

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  7. It's known that a diet high in carbohydrate "burns off" B vitamins. Probably some more than others, but this has been a known quantity for some time now. I am given to understand there may be similar issues with vitamin A and chromium. And the more carb you eat that breaks down into glucose in the body, the more vitamin C you need, because they complete for the same receptors. (For anyone who doesn't already know this, animals that can make vitamin C make it from glucose.)

    So there are lots of ways a high-carb diet makes it harder to get good nutrition, quite aside from the effect of carbs on insulin and perhaps leptin resistance and other issues. Which makes the current trendy-trend-trendiness in the Paleoblogosphere for slamming the low-carb movement all the more disturbing.

    I have my own experience with a vitamin deficiency that didn't show classic signs. I think I was vitamin A deficient for several years, and that my deficiency also hurt my daughter, who was born with health problems that seem to point to lack of vitamin A. Her kidneys and ureters did not develop correctly (they work, but she had problems for a while and one kidney is still noticeably smaller than the other) and her teeth started decaying within six months after they first erupted. Vitamin A mediates nephron and ureter development, and also assists in the development of enamel in unerupted teeth.

    Then on top of that I had horrifically heavy periods after my cycle came back. I was worried I might have endometriosis, and I am all too aware of how hysterectomy-happy a lot of OB/GYNs are, and I didn't want to do that over what amounted to an inconvenience. Went looking to see if anyone was managing it with diet. Around the same time I was reading more stuff at the Weston A. Price Foundation website and caught some little mention about vitamin A's association with reproductive health. I decided to try supplementing A from fish liver oil to see what would happen.

    Bingo.

    It took me another couple of years of off-and-on reading and research to figure out the kidney/ureter development and enamel angles on vitamin A deprivation. In the meantime, I can tell when I haven't been getting enough A because the weird cramping comes back and the periods get heavier.

    I also learned that between 40 and 50 percent of the population can't convert enough beta carotene to get a good amount of A out of it, and I don't know whether that was everybody or just healthy people, and infants and children can't make the conversion at all. They are now telling pregnant women not to eat liver because "vitamin A causes birth defects" even though it's been shown in research that embryos can control how much maternal vitamin A they absorb. It's actually *synthetic* A that causes problems, but no one's bothered making the distinction.

    The Mayo Clinic says urinary tract defects are the most common class of birth defects in the United States. I'm pretty sure I know why.

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  8. Dana, how much vitamin A per day have you been taking in? Is there vitamin D in the fish liver oil too?

    Two months ago I ate about 100g of beef liver every day for a week and got bad cramps in my right biceps and left latissimus dorsi after a sprint, which had never happened before. I don't know if it was the vitamin A, copper, an indirect effect like abnormal blood Ca, or maybe just a coincidence. For about 10 months now though my vision has been the slightest bit off. I'm still 20/20 and have no peripheral problems, but I definitely notice a slight light sensitivity and general difference.

    Chris Masterjohn has proposed blue-eyed [me] people needing more A. I did the 23andme analysis with Promethus, and it said I am bad at beta-carotene conversion--eat lots of dairy, but it may not be enough.

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  9. Just wanted to note that thiamine is depleted by polyphenols in foods other than coffee and tea. In fact there are quite a few foods and other compounds (like molds) that produce thiaminase enzymes, which basically destroy thiamine.

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