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Nutritional Brain Bomb: Thiamine Deficiency

Vitamin B1 is essential for proper brain energetics.

People maligning a modern diet tend to poke fingers at the the last 30 - 40 years. During this time obesity became a majority issue in the United States, and diabetes and metabolic syndrome afflicted many millions. However, from a nutritional perspective, diets 100 years ago weren’t that terrific either. Obesity was uncommon, but among certain populations, major vitamin and mineral deficiencies were rampant and deadly. Today, it's rare to see scurvy or other famously maritime deficiency diseases aside from serious long-term alcoholics or eating disordered individuals.

One of the more dangerous deficiencies to our brains (and one found not uncommonly in alcoholics) is thiamine deficiency, also known as Wernike's Encephalopathy (and if you are very unlucky, Korsakoff's Psychosis). A new subset of patients aside from chronic alcoholics need to worry about this issue too, as I mentioned in the Chris Kresser Podcast Episode 13, there are many case reports in the literature of psychosis and weird psychiatric and neurologic syndromes popping up in gastric bypass patients several years after the surgery. Copper, iron, and B12 are all problematic for post gastric bypass patients, and so, apparently, is thiamine (vitamin B1).

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Alcohol interferes with the intestinal absorption of thiamine, so that people who obtain the majority of their calories from alcohol are unlikely to get quite enough thiamine. A "clinical pearl" taught in medical school is to double (in your mind, not in the chart!) the amount of alcohol someone tells you he or she drinks. (Hundreds of honest people now vow to halve the amount of drinking they admit to… then realize in truth they already have been…). I've heard every sort of vast quantity of alcohol use daily from "a quart of Jack" or "a 30-pack of beer" to "17 boilermakers" and "whatever I can get my hands on."

Who cares if you don't get enough thiamine? Well, as we know, your brain loves energy, as do the rest of your nerves. And good old vitamin B1 is a cofactor to a zillion energetic reactions. If you burn glucose, you desperately need your thiamine. To quote my old Harrison's Principles of Internal Medicine, 14th Edition (page 2455):

Thiamine is a cofactor of several enzymes, including transketolase, pyruvate dehydrogenase, and alpha-ketoglutarate dehydrogenase. Thiamine deficiency produces a diffuse decrease in cerebral glucose utilization and results in mitochondrial damage… electron microscopy shows disintegrating mitochondria, chromatin clumping, and swelling of degenerating neurons…consistent with excitotoxicity.

Yikes! Even if the bigger words are mysterious, let me assure you that the picture is very bad. Dying, rotting neurons and a smokey ruin of your precious brain. Certain areas of the brain, such as the mammilary bodies and parts of the cerebellum seem particularly vulnerable, as they may have some of the highest glucose utilization in the brain. The heart, being a high energy-using fellow itself, is also vulnerable to thiamine deficiency. Nervous system symptoms from thiamine deficiency is also called "dry beriberi" whereas cardiovascular involvement is known as "wet beriberi" or "sailor's asthma."

What are the symptoms? Classically, the clinical triad is paralysis of certain eye movement muscles known as "ophthalmoplegia," problems with balance and walking (often a wide-based, shuffling gait) known as "ataxia," and confusion. Only 1/3 of patients will present with all three; most are very disoriented, inattentive, and sometimes agitated. If a profoundly thiamine-deficient patient shows up in the emergency room and is given straight-up D5 IV drip (D stands for dextrose, which is basically glucose), this will confound the problem and worsen the symptoms which can include stupor, coma, and death. (ER docs and nurses really try hard not to kill folks by giving them the standard IV in the emergency room). This fact is why someone with a history of alcoholism will instead be given a "banana bag" which contains folate, 100 mg thiamine, magnesium, and a multivitamin solution. This combination makes the bag yellow instead of clear like most IV solutions (thus the name). Acute thiamine deficiency (Wernike's encephalopathy) can be cured with 50mg thiamine a day until normal eating resumes.

Chronic thiamine deficiency is not curable and can result in a particular type of brain syndrome called Korsakoff's psychosis. The afflicted will have poor memory and confabulate like crazy: meaning, you ask him a question, and he will not know the answer, but he will make one up!

Well, most of you who are not members of the antique navies of the world and also without a 17 boilermaker a day habit or other genetic deficiencies of the pentose phosphate pathway will never experience such severe thiamine deficiency that you will get such dramatic symptoms.

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 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 — the connective tissue degrades and you spend a great deal of time in terrible pain as you slowly bleed to death internally. Preventing scurvy on a multi-year journey to the Arctic was essential.

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. 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 percent of the Japanese population 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.

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 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.

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, white flour and white rice are fortified to prevent a rather horrible death from subsisting on the raw refined materials. Gives one pause, doesn’t it, about eating them in the first place.

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Copyright Emily Deans, MD