Monday, August 26, 2013

Thiamin deficiency, altered circadian rhythm, and adrenal fatigue

Have you been diagnosed with adrenal fatigue?  Have you recently removed processed foods from your diet and had a tough go of it?  Have you been diagnosed with a magnesium deficiency?  Do you:
  • Drink coffee or tea
  • Drink alcohol
  • Binge on sugar or carbohydrates
  • Exercise excessively (Crossfit or endurance)
  • Have poor sleep
  • Have an altered cortisol rhythm
  • Have candida overgrowth
If you said yes to a number of these things you may be at risk for a thiamin deficiency.  What's worse, if you have cut out processed foods or grains you are probably not ingesting enough thiamin through diet and making your problem worse.  Let's take a look at this rarely discussed nutrient and how it may be contributing to your adrenal fatigue.

Thiamin 101
Thiamin(Also called thiamine or vitamin B-1) is an essential water-soluble B vitamin that humans cannot synthesize, they must get it from their diet.  Thiamin is involved in carbohydrate and amino acid metabolism and is used in the biosynthesis of the neurotransmitters acetylcholine and GABA(1).  The RDA for thiamin is set at 1.5mg per day and food sources of thiamin include cereal grains, yeast, pork, organ meats, beans, and nuts(2).  The problem is that other than cereal grains and yeast, most food sources only contain small amounts of thiamin.  Since thiamin is used in carbohydrate metabolism, eating high amounts of carbohydrates or performing physical activities that rely on the glycolytic energy pathway such as crossfit or longer distance sprinting activities increase a person's need for thiamin(2).  Other nutrients that are thought to impact thiamin status are magnesium and calcium, a deficiency in either may make a thiamin deficiency worse(1) 

Other lifestyle factors that are prevalent in modern society also negatively impact thiamin status.  Coffee and tea contain tannins that render thiamin useless in the body(3) in addition to the diuretic effect that caffeine has that increases the loss of B vitamins.  Alcohol also has a negative effect on thiamin levels both by preventing absorption as well as it's diuretic effect(4).  Wernicke-Kosakoff Syndrome(WKS), a disease of thiamin deficiency, is most often seen in alcoholics(1).  In addition to it's alcohol content, wine contains sulfites that destroy thiamin.

Diseases of thiamin deficiency including WKS and beriberi often present with neurological symptoms, but can include the circulatory system as in the case of wet beriberi.  Candida overgrowth can also lead to thiamin deficiency as yeast use thiamin in the first step of alcohol fermentation.  In addition, 3 strains of bacteria known to reside in the human small intestine and colon are known to produce enzymes that degrade thiamin in the digestive tract(1) which could become problematic if they overgrow.

Diabetes and high blood sugar can also induce thiamine deficiency and diabetics have been found to be deficient in thiamin(4, 5).  This is due, in part, to hyperglycemia causing increased loss of thiamin in the urine.  Since it is believed that this effect is due specifically to high blood glucose, whether insulin resistance is pathological due to diabetes or physiological due to low carbohydrate intake would be irrelevant.  In addition, low thiamin has been shown to impair pancreatic function leading to hyperglycemia(4) and thiamin therapy has been shown to improve hyperglycemia in diabetics(5, 6, 7).

Research on thiamin deficiency, the adrenals, and circadian rhythm

Thiamin and adrenal function

In rats, thiamin deficiency has been shown to have a fairly dramatic effect on adrenal function.  In a study looking at rats induced with thiamin deficiency, the rats experienced an exaggerated cortisol response to stress within 2 weeks, with a complete exhaustion of the adrenals within 4 weeks(8).  The adrenals increased in size throughout the study and the mitochondria within the area of the adrenals responsible for cortisol secretion became swollen.

In addition to the changes in the adrenals, liver glycogen levels became extremely low and the thymus of the rats shrank in size, indicating a compromised adaptive immune system.  This could be a potential mechanism by which candida can gain access to the body as the adaptive immune system is responsible for making T helper cells that would be in charge of removing candida, or any infection, from the body in the event the intestinal barrier becomes compromised.  Ironically, a thiamin deficiency may negatively impact intestinal permeability by thinning the microvilli and decreasing enzymatic secretions in the gut that digest protein and carbohydrate, including lactase(9).

Cortisol is not the only adrenal hormone affected by low thiamin status.  In a study also done in rats, rats with thiamin deficiency had a decreased aldosterone response to low sodium levels(10).  Aldosterone is the chief mineralocorticoid responsible for regulating electrolyte balance in the body.  When sodium levels become low, aldosterone is secreted to recycle sodium back in to the blood and dump potassium out via the urine.

Many of the symptoms associated with adrenal fatigue are due to an electrolyte imbalance, an issue I discussed here.  Having a decreased ability to regulate electrolyte balance will lead to a worsening of symptoms associated with adrenal fatigue.

Thiamin and circadian rhythm

Many studies have shown thiamin deficiency to disrupt circadian rhythm in mammals(11, 12, 13) and the change in circadian rhythm precedes the neurological damage associated with thiamin deficiency(11).  GABA is an inhibitory neurotransmitter in the central nervous system, meaning it is a calming substance.  GABA is considered an essential player in regulation of the circadian clock(14), and given thiamin's role in the biosynthesis of GABA, it makes sense that a thiamin deficiency would disrupt circadian rhythm.  In addition, the thiamin deficiency disease beriberi primarily affects the autonomic nervous system which is a central regulator of the circadian clock(14).

Anecdotally, many people who have undertaken a low carbohydrate diet have noticed a change for the worse in sleeping habits.  Since lowering carbohydrate intake always includes lowering grain consumption and thus thiamin consumption, this is a potential mechanism by which low carbohydrate diets may negatively impact sleep.  The problem may not be in the low carbohydrate status so much as low GABA caused by a lack of thiamin intake.  In people who periodically binge on sugar, overexercise, or drink coffee or alcohol the problem will be worse.  Carbohydrate intake could come in to play once adrenal insufficency sets in because in the absence of carbohydrate, cortisol is used to increase glucose output by the liver.  Also, since low thiamin has been shown to reduce liver glycogen storage, this would impact your ability to meet the brain's glucose needs when asleep.

Thiamin form and dosage

While I am a firm believer in getting your nutrients from food, several instances may prevent someone from being able to establish healthy thiamin levels through diet.  People who are using diet therapeutically to identify food sensitivities or improve digestive disorders with grain and nut/seed-free diets will most certainly not be able to get adequate thiamin from their diet.  A lot of these people also have mild to severe adrenal dysfunction so supplementation may be necessary to get them back on the right track.

Most forms of thiamin are water soluble and poorly absorbed from the digestive tract when compared to disulfide derivatives of thiamin.  Allithiamine(TTFD) is one of these derivatives, is found in garlic, and has been shown in studies to increase blood thiamin levels almost 10 fold(15).  This would be the equivalent to intravenous injection of the standard water soluble forms of thiamin.  This makes allithiamine the preferred oral form of thiamin for reversing deficiency.  There are no studies on a recommended dosage for allithiamine, but most recommendations indicate that there is no upper limit to intake and therapeutic dosages range from 50mg a day up to 300mg. 


Thiamin deficiency appears to be a pretty strong player in adrenal fatigue and altered circadian rhythm.  The RDA for thiamin is set at 1.5mg per day by the USDA, something most people eating a grain restricted diet such as the Paleo diet, specific carbohydrate diet(SCD), or GAPS diet will not be able to attain from food.  Of the three, it is possible to get enough thiamin on a Paleo diet as it allows the consumption of nuts and seeds.  While the Perfect Health Diet does allow white rice consumption, white rice has been stripped of it's thiamin which is why it is recommended to supplement with thiamin.  In fact, beriberi was prevalent in Japan for just that reason(1) as it was found that the disease was caused by an imbalance between energy ingested from carbohydrates and one of the micronutrients(thiamin) required for their oxidation(14).  This was discovered in birds as white rice and/or starch consumption in the presence of inadequate thiamin consumption led to neurological damage similar to beriberi(1) and was reversed with thiamin intake.

All of this is not to say that I believe the RDA for thiamin is accurate for everyone.  I still hold to my statement in my last blog that there is unlikely any way our paleolithic ancestors got 1.5mg of thiamin in their diet.  However, their carbohydrate consumption was likely quite low, they didn't regularly consume alcohol or coffee, and they were under far less chronic stress than we are.  It is also possible that their gut flora contained a strain of bacteria that manufactured thiamin for them, and as we relied more heavily on grain consumption that strain disappeared or was significantly reduced in our gut and replaced with bacteria that we required or inadvertently overfed with our dietary choices.  In fact, research has found that there tend to be 3 different enterotypes of the human microbiome that produce different levels of enzymes capable of producing varying levels of different vitamins.  The microbiome of enterotype 2, which is high in the bacterial species Prevotella, shows higher activity of enzymes responsible for the production of thiamin(15).

This is one way in which you cannot really say that our genes are not different from those of our paleolithic ancestors.  While it may be true that the genes within our bodies haven't changed, our gut flora has.  This is an effective change in our genome as we may no longer possess the ability to extract a particular nutrient from our food, or we become too good at extracting nutrients that can be detrimental.  In this way, the choices we make now can have serious ramifications on the way we function down the road as well as the diseases we experience as a species.

I do not want people to read this as saying a grain free diet is not the way to go.  It is still my belief that the Paleo diet is the best diet for people to consume.  One takeaway I hope people eating the SCD or GAPS diets will get from this is that they should be supplementing with thiamin until their condition gets better and they can move on to eating nuts and seeds.  Many of these people have adrenal dysfunction and a thiamin deficiency will only make their condition worse. 

I enjoyed this little diversion from my no deficiency diet research, but now it's back to work.