Sunday, August 21, 2011

Nutritional Brain Bomb - Thiamine Deficiency

Yes, I will get back to the carbohydrate insanity series shortly.  But in the comments of the second post, Jack Kruse and Itsthewooo noted that studies with respect to alcohol, blood sugar and violence could be confounded by other nutritional deficiencies.  Which is absolutely true.  I have to say, it is rare to see scurvy or other famously maritime deficiency diseases aside from the serious long-term alcoholics who frequently populate the emergency room.  As one of my attendings in medical school put it, the "Three B diet" (beer, bologna, and bread) is not one likely to come up roses when thrown into a nutritionist's calculator.

So since I seem to be blogging an awful lot right now, I thought I would throw in an instructional primer on brain issues and thiamine deficiency, also known as Wernike's Encephalopathy (and if you are very unlucky, Korsakoff's Psychosis).  And a new subset of patients aside from chronic alcoholics need to worry about this issue too - as I mentioned in The Healthy Skeptic Podcast Chris Kresser Dot Com 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 - though copper, iron, and B12 are all problematic for post gastric bypass patients, so, apparently, is thiamine (vitamin B1).

Wikipedia Commons


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."   (Shoot - another "clinical pearl" segue, for any medical students or residents reading this blog - the opposite is actually true for any savvy opiate abusers - often the dose of methadone given to prevent withdrawal is scaled to the amount the patient says he or she uses, rather than using vital signs and clinical picture as is the gold standard, so he or she will often increase the self-reported amount to get more methadone off the bat.  And ALWAYS call the methadone clinic to confirm the chronic dose before you write the order for the hospital stay - 160 mg of methadone is a common clinic dose but can stop the breathing of someone not used to that much.)

So 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 Harrison's Principles of Internal Medicine, 14th Edition (yes, I am old, 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 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, which 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.  But the case of vitamin B1 does serve to illustrate the importance of appropriate nutrition for our noggins to work correctly.




29 comments:

  1. Dear Dr. Deans,
    I realize this is not your consulation, but you may answer this in general: If someone, me, say, has been drinking heavily for 20 years and has stopped (yay!) - which kind of supplementation would you recommend to help my poor abused body deal with the repairs?
    I credit my primal/paleo diet with the fact that I was able to stop - it lowered my craving for alcohol quite a bit.
    Any input would be appreciated as to diet, supplementation and anything else you may think of.
    I'm a woman and 41 years old.
    Kind regards Ulla

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  2. Great job quitting a 20 year habit! I'd say make sure you are getting plenty of B vitamins, especially, and then everyone can buff up the minerals. I think of the B vitamins as a team sport - don't want to have too many or too little of any of them. Most processed food is supplemented with folic acid in the US, and unless it is methylfolate I would avoid it. If you aren't eating processed food, dark leafy green veggies and liver are good sources of your B vitamins, but you might want to invest in a b complex also (just watch the folic acid). I take a multi-mineral called "thyroid synergy" (it has some selenium, iodine, zinc, a bit of chromium, etc.) and extra magnesium myself. There are other commenters who are more of an expert at the vitamins. They might have some ideas.

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  3. While we're on the subject, I have been meaning to ask you where you read about refined flour and vitamin deficiency induced mental illness like you mentioned the ChrisKresserdotcompodcast about "healthy" skepticism. Or was that another one? I forget. But it was about refined flour and mental illness in Europe and sounded very interesting.

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  4. Thank you very much - and thanks for the good work on the blog also.
    Kind regards, Ulla

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  5. Doc Deans, what is your view on the synthetic thiamine i.e Sulbutiamine?

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  6. Oh boilermakers... I'd never heard the term until I started doing medical interviewing at the VA, then it seemed like I was a total square. Anyone who was anyone did boilermakers!

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  7. Stabby - I have a fondness for old papers and old descriptions o mental illness. We had a class is residency with a lot of old papers... mostly say it there

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  8. Victoria - I was first introduced to the term 2nd year med school, and yeah, we had to look it up too.

    Rob - all I know is what I read in Wikipedia. Looks interesting, and as far as I know there is no thiaminE overdose syndrome (the 100mg in a banana bag is about 70-80 times the RDA). I think you asked me about this last year - I'll try tonchase down a paper.

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  9. "If you burn glucose, you desperately need your thiamine."

    Hey Emily,

    Without starting a macronutrient debate, does this mean that, other things being equal, a reduction in dietary carbohydrate also reduces the need for thiamine?

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  10. Speaking of being old...I remember reading in Adelle Davis's "Let's Eat Right to Keep Fit" that the utilization of B-complex vitamins was influenced by their ratio to one another. Too much or too little of a single B-vitamin can either increase the need for, or limit the function of, the others. This has always made me wary of supplementation.

    Any thoughts?

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  11. Sam - I'll quote Derrick Lonsdale in his 2006 paper "A Review of the Biochemistry, Metabolism, and Clinical Benefits of Thiamine and Its Derivatives" - "Thiamine plays a vital role in the metabolism of glucose. Thus, emphasis is placed on the fact that ingestion of excessive simple carbohydrates automatically increases the need for this vitamin. This is referred to as high calorie malnutrition." Beriberi was originally described (as far as I know) in nations in which the people ate white rice as a staple. Whole grains are a decent source of thiamin, but refined grains are not.

    Yes, the B vitamins scare me a bit as there are zillions, and the folate cycle is hella complicated. I hardly ever recommend too much more than the RDAs for anything - the exception being level-based vitamin D. It also seems to me that chromium is important. But common sense being common sense - if you eat a nose to tail animal, fruit, veggie, starchy root veggie, nut and seafood diet and you exercise, you are eating a lot of nutrient-rich food and are likely to be okay. The moment you add in white rice as a significant portion of your calories, you start to need to take that multivitamin "insurance policy" Paul Jaminet talks about.

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  12. I'm going to do the insulin resistance/carb/mood post in a day or so, and I'll follow up with another thiamine post.

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  13. I'm taking Step 2 tomorrow and I'm sure there will be at least one question on Wernicke's or thiamine before D5W! And I had a practice question recently that involved a psychotic women with auditory hallucinations telling her not to eat vegetables, and the answer was folate deficiency.

    Thanks for the tip re methadone dosing. I'll be having a boilermaker after the test to celebrate. :)

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  14. Good luck Tom - I thought the step2 was kinda fun, much more so than the step 3 - honestly that methadone thing is the one bit of info I hope my med students really absorb each fall when they take my class :-)

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  15. Note to self... all politicians may be suffering from chronic thiamine deficiency...

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  16. @Sam Knox......I have treated many booze hounds with thiamine deficiency who had endstage Korsakoff's and they imporved tremendously on ketogenic diets behaviorally......they still confabulated because their mamillary bodies were necrotic (great MRI findings) but thiamine deficiency can be avoid by a strict ketogenic diet. It is rarely done in medicine any longer. I tried to order a tube fed ketogenic diet today in the ICU for a patient with severe pregnenolone steal syndrome who I did a monster spine reconstruction on in the face of a severe autoimmune spine condition and I was told by the dieticians in the hospital we dont do that any more? So I consulted a non hospital dietician who made it up herself and brought it in. This is why medicine is in trouble. The cookbook rarely meets the needs of everyone these days. For ETOH abuse recovery I use PQQ, NAC, Sillymarin, B complex vitamins, Choline, with high dose of Vitamin C and I always replace vitamin D and K2 simultaneously. On the neurotransmitter side try to minimize the leaky gut to foster formation of GABA in the brain and spinal cord. GABA is a benzodiazepine like NT and it really helps a recovering brain from booze.

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  17. [Posting for my wife Laurie, who is the biochemist in the family and who has been extolling the dangers of wheat for some time now]

    DR Deans: you are a genius. This may not be the correct spot to comment on Jimmy Moore, but I just listened to your interview with him- spectacular. Please finish the '4' brain things. You said micronutrients and energy. The other two ? Too many toxins (like gluten), too much inflammation?, not enough brain healthy animal fat and cholesterol?

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  18. A low CO2 on blood work (below 25) is said to be assoc with low thiamine. That's from the old nutrition docs. Makes sense as the Krebs cycle wouldn't be "spinning" well and throwing off sufficient CO2.
    I suspect an alcoholic, recovering or not may have a life long need for B support.... at least some brewers yeast. The better companies like Thorne Research and DFH are using MTHF and methylB12 in their formulas.
    Love your blog, love your willingness to learn, your blog is pure nutritional yumminess.

    Robert

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  19. John - I'm definitely in favor of the Bs, D, K2 (my winter supplement has both in one pill) - yoga can increase GABA, btw… I like choline in eggs, a little torn about krill oil (caused anxiety in a few of my patients), I've also had mixed results with NAC, but will often give it a try as it is cheap and seemingly beneficial short term for many organ systems with no major short term downside that I can theorize.

    Joe/Laurie: Thanks! Um, yeah, I was wondering when that whole 4 things that I didn't mention in Jimmy's podcast was going to be noticed… micronutrients, energy, avoid toxins (inflammation, infection), and… I can't remember. But probably it had something to do with how statins are BAD.

    7dfetc. - thanks! I'm going to look into folate after the next couple of posts… already have the first paper lined up.

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  20. Never had any medical education, but nursing education was full of silly questions like this.

    For example, re: the psychotic woman with auditory hallucinations instructing her not to eat vegetables (implicating folate deficiency as a cuase of her psychosis)... well this question is flawed for a few reasons. one, vegetables are a poor source of folate due to our food supply being crap, most people get their folate from bread products and pasta.
    Two, if the hallucinations are instructing her not to eat vegetables, therefore she has become folate deficient, therefore psychotic, this ignores the obvious problem that her psychosis preceded the lack of eating vegetables. It suggests a low grade psychotic thinking must have been in place before hand.

    I understand the point of the question is to test the student's knowledge that folate deficiency can lead to psychotic thinking, but I get so caught up in the poorly constructed nature of these word problems, it's a bit distracting. I'm usually quite good at solving these problems (and did very well on all tests for this reason) but still, STUPID.

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  21. @john

    I think it is awesome that you are applying your knowledge to help your patients. If only more doctors had this courage.

    Dieticians are annoying. For some reason they think they are more knowledgable than physicians, and routinely try to overstep physician orders. You KNOW the real reason the hospital dietiicans refused to do the ketogenic diet is because it terrified them to do it. It would be like asking a vegan to cook up an awesome quarter pounder. You freaked them out and they said what they had to say to avoid participating in what they thought was an insane, blasphemous dietary prescription.

    It's like, STFU and go back to telling people to eat starches for health and other government propaganda you were brainwashed with in college. I've never met a dietician who had any scientific curiosity or knowledge beyond the standard propaganda.

    I thought it was rather standard for recovering booze hounds to be given scripts for benzos, such as librium, as the primary mechanism of action of alcohol in the brain is on GABA and targeting this system reduces most of the withdrawal effects as well as cravings.

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  22. Yes, benzos are standard treatment for acute alcohol detox for GABA reasons - though some places just use antiepileptics.

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  23. Does GABA as amino acid supplement cross the blood brain barrier? Most articles I read state it does not, but many people report benefits.

    Glutamine is a precursor to GABA and it also helps leaky gut if I remember well.

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  24. R2D2 - L-theanine in green tea is supposedly a nice GABA enhancer. NAC will also do a nice anti-glutamate trick. Yoga will work too. GABA itself would be useless to take, and there are issues with glutamine itself.

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    Replies
    1. Gaba under the tongue works well…does definitely cross the so-called blood-brain barrier. The gut-brain connection as they say...

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  25. I have tried sulbutiamine (fat soluble derivative of B1), it is stimulant.
    http://en.wikipedia.org/wiki/Sulbutiamine

    There are other forms of thiamine

    http://en.wikipedia.org/wiki/Allithiamine

    http://en.wikipedia.org/wiki/Benfotiamine

    I first heard of allithiamine here http://ctheblog.cforyourself.com

    Benfotiamine I see it is used by life extensionists as anti glycation agent.

    Note : I figured out why I did not have a name here with AOL login, I had left "display name" blank, sorry. It can be set here:
    https://bill.aol.com/SPortal/jsp/morfchange_contact.jsp

    I comment because I see another person using AOL ID.

    I appeared as c0c820de-7935-11e0-9321-000bcdcb471e

    What is R2D2?

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  26. Yes, thiamine deficiency is typical of the refeeding syndrome, as well as Wernike's Encephalopathy and Korsakoff's Psychosis.

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  27. "minimize the leaky gut" Folks treating alcoholics should look at the research on kudzu root.

    "However, it is not clear whether the improvement of intestinal permeability is associated with the prevention of Puerariae radix on alcohol-induced liver injury, like as dietary components decreases endotoxemia and hepatic
    injury by restoring a normal permeability after alcohol intake in rats (Keshavarzian et al., 2001).

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  28. I found this discussion when I did a Web search for "Korsakoff" in connection with "Sulbutiamine" and just wanted to add that a relative of mine was suffering from all the symptoms. I was told by his social worker that he's classified as Korsakoff patient (he himself couldn't even tell because he forgot everything). Current treatment isn't very effective, specially if the patient continues to drink. The main reason why treatment is not effective is because only minimal quantities of thiamine can cross the blood-brain barrier, so even massive supplementation has only minimal therapeutic effect. I did some research and found out about Sulbutiamine being a form of thiamine that crosses the blood-brain barrier readily, so I procured some for him. Once he started taking it, his memory began to improve almost immediately, and after a few weeks, subsequent tests could not find evidence of Korsakoff's. His memory never returned to full capacity, but now it is "just" poor memory, whereas before there didn't appear to be any short-term memory at all (he'd ask a question, for example, and, after you answered it, he'd as the same question again).

    There are so many alcoholics suffering from this condition and it is usually during the last stages of their lives. I find it discomforting that no research appears to have been done into treating Wernicke-Korsakoff sufferers with fat-soluble thiamine derivates like Sulbutiamine. It might have something to do with the nature of this affliction (considered to be self-inflicted) and that those afflicted are seen as a burden to society.

    Anyway, in the apparent absence of research, I thought, perhaps, personal testimony might be of interest to some.

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