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Tuesday, 14 August 2012

The Role of Vitamin Fortification in the Obesity Epidemic

The beriberi weight loss diet; fortification for the "fattening carbohydrate" theory of obesity.

The obesity epidemic is more advanced in wheat-eating countries and countries with a high intake of processed carbohydrates, and less advanced in countries with a high intake of carbohydrate from polished rice.

It has been noticed for more than a hundred and fifty years that animals accumulate fat on a low-fat, high-carbohydrate diet. Metabolism favours lipogenosis; the steady state (isocaloric) metabolic flux is carbohydrate => fatty acids => CO2 + H2O.

There are exceptions to this rule; lipogenesis is decreased to 5% of normal when caloric intake is inadequate to maintain weight. And lipogenesis is decreased when the B vitamin thiamine is deficient in the diet.

The metabolism of carbohydrate greatly increases the requirement for thiamine (anuerine, vitamin B1). Thiamine is the required co-enzyme for the first step in the conversion of pyruvate to acetyl-CoA, which is how energy from glucose enters the Citric Acid, Krebs, or TCA cycle.

Conversion of pyruvate to acetyl-CoA is required for conversion of glucose to ATP and also for conversion of excess glucose to fatty acids (which requires ATP).

Thiamine is one of the B vitamins and plays an important role in energy metabolism and tissue building. It combines with phosphate to form the coenzyme thiamine pyrophosphate (TPP), which is essential in reactions that produce energy from glucose or that convert glucose to fat for storage in the tissues. When there is not enough thiamine in the diet, these basic energy functions are disturbed, leading to problems throughout the body.

In a situation where the ability to convert pyruvate to acetyl-CoA is not restricted by the availability of thiamine, some individuals will experience increased appetite and fat storage. This is a normal adaptation to store energy against future lean periods (fat being the body’s default fuel).
When thiamine is severely depleted, as in alcoholism, energy cannot be stored as fat and even the normal fat deposits of lean individuals shrink.
The exception is beer drinkers, who can gain fat (”beer belly"). Beer is a better source of thiamine than other alcoholic drinks. 

In most western countries white flour is fortified with vitamins including thiamine. In America, white rice is also fortified. 75% of white bread was fortified by 1942 in the USA. Since then fortification and supplementation has spread through the food supply. Vitamins are popular and thiamine is known to be non-toxic.

The thiamine content of a modern multivitamin is about 10 times the amount issued to prevent beri beri in troops serving in WW2.
This is the oldest formulation I can find data on:
Vitamin waters and energy drinks are popular sources of extra thiamine (and carbohydrate). In New Zealand thiamine is added to breakfast cereals, yeast extract spreads, Milo and other popular chocolate drinks; fortification is pervasive in the food supply.

What happens if thiamine intake is marginal on a high-carbohydrate diet? Surely the conversion of carbohydrate for immediate energy needs would be favoured, and the consumption of extra carbohydrate to be stored as fat would be suppressed. And we do in fact find that deficiency of thiamine causes anorexia. Imagine a diet where carbohydrate is not fortified, and thiamine comes from pork, fish, dairy etc. eaten with polished grains (these foods are of course also eaten in the USA and Europe with fortified grains), or with root vegetables which supply more thiamine than polished grains but less than fortified foods.

Thiamine on such a diet would be adequate for good health but would not favour extreme accumulation of fat; accumulation of pyruvate would work to suppress appetite if excess carbohydrate was consumed.

The non-glucose related TPP-dependent enzyme, branched-chain ketoacid dehydrogenase, catalyses the production of acyl-CoA derivatives from branched-chain amino acids in liver and muscle.

Professor Bruce Ames has published a number of reviews on the Micronutrient Triage theory; that micronutrients are apportioned differently when scarce. Mild deficiency of selenium, for example, spares the systems affected by severe deficiency. Short-term survival takes precedence over long-term survival. In the case of thiamine, fat storage is a long-term survival project.

In a country such as New Zealand, with a large impoverished underclass (“let them eat carbs!”),  and a high rate of alcoholism due in part to tradition, in part to pro-alcohol governments washing their hands of responsibility for issues of pricing and availability, thiamine over-abundance undoubtedly prevents much harm. We are not discussing a toxic effect of thiamine, nor a benefit from deficiency, but the likelihood that marginal thiamine status, and the metabolic adjustments this requires on a high-carbohydrate diet, was preventive of obesity in past populations eating white bread, white sugar, polished rice, boiled potato, and so on.
This is not meant to imply that these populations were healthy as a result.

The association between vitamin fortification and obesity has been well studied. There is indeed a strong association (with a 10-year delay).  

In this paper, obese individuals store and recycle thiamine more than controls.

The bottom line: even if this hypothesis is correct, no responsible person would advocate thiamine restriction as a response to the obesity epidemic or a treatment for obesity. Thiamine-replete populations are healthier, even if they are fatter, and the fat storage process that thiamine catalyses is not pathological in itself. Carbohydrate restriction, on the other hand, is a practical way out of any dilemma, as it reduces the requirement for thiamine at the same time as exposure to fortified foods and fattening carbohydrates is reduced.
In fact, high-fat diets can be used to prevent thiamine deficiency:

Thiamine is also essential for production of acetylcholine and GABA. These are vital neurotransmitters and deficiency of thiamine causes severe neurological and psychological symptoms and, if prolonged, nerve and brain damage, due in part to disordered glutamate and GABA signalling and oxidative stress. In alcoholism or severe malnutrition this is called Korsakoff’s syndrome.
pentose phosphate pathway

A classic symptom of early thiamine deficiency is a “sense of impending doom”. This is like something from the weird tales of H. P. Lovecraft. You feel in your soul that your doom is near; exactly when, how, or why you have no idea. This literally dreadful sensation might be familiar to anyone with experience of amphetamine or cocaine abuse. It is probably related to low GABA status.

Raw fish can contain a thiamine-destroying enzyme, thiaminase. Perhaps this also helps to explain the popularity of sushi among dieters, and the low incidence of obesity in high-carb cultures like Japan and Okinawa.
Thiaminase can also be produced by some gut bacteria, perhaps as a way of competing with other commensal species for carbohydrate released from resistant starch.

Thiamine is released by the action of phosphatase and pyrophosphatase in the upper small intestine. At low concentrations, the process is carrier-mediated, and, at higher concentrations, absorption occurs via passive diffusion. Active transport is greatest in the jejunum and ileum (it is inhibited by alcohol consumption and by folic deficiency). Decline in thiamine absorption occurs at intakes above 5 mg. _ Wikipedia

The presence of anti-thiamin factors (ATF) in foods also contributes to the risk of thiamin deficiency. Certain plants contain ATF, which react with thiamin to form an oxidized, inactive product. Consuming large amounts of tea and coffee (including decaffeinated), as well as chewing tea leaves and betel nuts, have been associated with thiamin depletion in humans due to the presence of ATF. Thiaminases are enzymes that break down thiamin in food. Individuals who habitually eat certain raw freshwater fish, raw shellfish, and ferns are at higher risk of thiamin deficiency because these foods contain thiaminase that normally is inactivated by heat in cooking.

In fact, it looks as though anti-thiamine factors of all classes might be prevalent in precisely those diets most often called in evidence to falsify the carbohydrate-insulin hypothesis of obesity: for example,

In the Philippines, the Tagalog word for beriberi is 'bangungut' which means nightmare and classically death occurs in sleep after a heavy meal consisting of rice and fish (Lonsdale, 1990). The thiaminase in the fish may compound an initial marginal dietary thiamine deficiency and can be fatal.

Some bacteria (e.g. Bacillus thiamineolyticus) are also capable of destroying thiamine. It has been reported that 3% of Japanese show a thiamine deficiency due to this cause. Thiaminase bacteria have been frequently isolated from human stools in Japan and it was reported that the thiamine levels in the blood of these patients was low in spite of adequate intake largely due to the destruction of thiamine in the intestines (Bhuvaneswaran and Sreenivasan, 1962).


John said...

I believe that in one of the Burr and Burr papers, they reference another researcher that suspected "efa deficiency" was in fact a thiamine deficiency, which was then called the anti-neuritic vitamin.

If there was a thiamine deficiency, perhaps that explains the high metabolic rate, which is common in efa deficienct mice/rats, but not always present.

John said...

Those rats and mice of course would be consuming more carbohydrate. Does thiamine deficiency increase metabolic rate or simply reduce appetite and fat storage? While this is a possible factor, the miniscule amount of fat required to drastically change physiology makes me question that idea.

majkinetor said...

Did Lovecraft have B1 deficiency ? Looking at his biography, its possible, even probable :) If that was the case, I am off ASAP to buy few tones of B1. I am not ready for the Cthulhu, yet !

I recently started eating a bit more carbs while taking B50 for some time and gained 2kg after a year of ideal weight. Is it the B, or the carbs ? I think carbs. It looks that for me, keeping carb intake between 50..75g per day is absolute must.

Ames writes a lot about B vitamins in order to optimize metabolism. For instance at he says: Approximately 50 different human genetic diseases that are due to a poorer binding affinity (Km) of the mutant enzyme for its coenzyme can be remedied by feeding high-dose B vitamins, which raise levels of the corresponding coenzyme. The mechanism behind triage theory is increase in Km with aging and mutations. So, even if B1 is anorexic, mild deficiency leads to myriad of problems.

There are far better ways to fight obesity with vitamins. Vitamin A, for example, is sort of opposite of B1 - the higher your A level, the leaner you are and vice-versa ( The effect is related to dose, and ofc, you have myriad of other kewl effects. People scare of megadosing A. Pauling recommended 25000IU/day. International vitamin A group recommneded maintenance dose of 25k-30k IU per day and therapeutic of 100k-150k for everybody apart from reproductive females. Its surprisingly hard to overdose unlike the hype you hear around - I read all reports available of vitamin A safety, and apart from few hard core sick individuals people need to take 100K for decades to overdose. Vitamin D & K2 will reduce this chance to none (so cod or shark liver oil will be perfect supplement). D will also help with other obesity problems like inflammation.

tess said...

how VERY interesting.... you (and your commenters) have just given me a huge number of things to read up on!

Puddleg said...

@ John, I am really just looking at thiamine as part of the human experience; I think the historical evidence is compelling, and the term "marginal status" keeps coming up.
Marginal status is probably the evolutionary norm for lots of things.
Lipid and protein have a sparing effect on TTP. So at some stage they are also factors?
Because thiamine seems to have a low Km (riboflavin or biotin deficiency is harder to produce experimentally) and because it is so exclusively a carbohydrate metabolizing vitamin (glutamate and GABA are produced from glucose), it seems to justify singling out.

@ majkinetor,
I am a big fan of vitamin A. I think deficiency RDAs arise from alcoholism, which is pervasive in society and turns retinol toxic.
Retinol metabolites govern Treg activation, in other words immune tolerance and Th2 austerity.

I think thiamine potentiates excess carbs, though 2 Kg is not much.
But excess carbs without thiamine will produce dropsy, which was more common in historical times.
I think this supports Paul Jaminet's position; don't eat fortified foods, don't supplement B vitamins for no clinical reason, get properly nourished from animal food instead.

majkinetor said...

The only problem with PJ position being that "properly nourished from animal foods" is meaningless therm, unless you own that animal and its land.

The other problem with PJ position is his insistence on safe carbs or even essential carbs (i.e. to prevent mucus problems etc.) without any real evidence whatsoever, which makes his position political rather then scientific (probably in order to find fine line between sustainability of PH diet & well being so more people will follow it with all the glory and richness that comes with it)

Puddleg said...

Although I don't think sugars are essential, I don't see why they can't be medicinal, much as ketones, or SFAs are, in the right context.
I eat store-bought, mostly non-organic meat, and it's fine, but then I live in a country without feedlots, where most meat is still pastured.
Any diet plan walks a fine line between prescriptive and permissive.
Even Atkins is often too permissive for my liking.

Puddleg said...

This just in:
"The discussion concluded with the vexed issue (once again) of carbohydrates versus calories – All agreed that significant calorie restriction is hard to achieve and restricting a single food class may be easier, and there was general consensus that carbohydrates probably have greater adverse metabolic effects than other food classes, and full consensus that this needs to be properly researched."
Gaery Taubes part of the discussion.

greg said...

"Sense of impending doom".

Zounds! This is interesting. About three years back I had a raging case of Cushing's Disease. Cushing's, for those unaware, occurs when the body if flooded with the natural steroid cortisol, typically (as in my case) through a tumor on the pituitary gland. For me this abundance manifested itself in numerous ways, including massive weight gain, constant hunger, "diabetes" etc.

Then, almost as if a switch had been thrown, I rapidly began to experience an entirely different set of maladies, including massive weight loss (of muscle, not fat) tissue, near hypothermia, anemia and most memorably...a very odd, ill-defined sense of my immediate death! It's hard to describe exactly, except I was convinced that for some vague reason I would not live to see another month, and this notion did not seem to stem from some kind of critical analysis of the riot going on within my body (nor thoughts to commit suicide).

Cushings's is also linked with massive depression (another fact to which I can personally attest), so now I'm wondering if vastly-increased amounts of cortisol inhabiting the body 24/7 have some sort of effect on thiamine as well? It definitely does on the body's ability to retain potassium, one thing.

Wow! After having surgery to remove the tumor about two years ago I've fully recovered, but I've continued to wonder the exact reasons for that "sense of doom" business (which never returned, nor has the depression nor any of my other symptoms I'm happy to say).

Perhaps some bright researcher will study the relation between thiamine and natural body steroids, and their effects on the hypothalamus etc.


Puddleg said...

It is possible that the rapid weight gain might deplete thiamine after a while, or sequester enough TPP in fat cells that the brain became relatively deficient. If people who become obese naturally are thiamine super-storers, then people who are driven to gain by something like Cushing's might not be so well adapted.
I read a true story about a Nazi rocket scientist in hiding from the Allies after WW2 who took cortisol and gave himself Cushings for a disguise!
It didn't work.
Cortisol is the connection between circadian rhythm, shift work, diabesity, and the benefits of intermittent fasting.

Puddleg said...


Puddleg said...

@ Majkinetor,

I just reread this comment of yours:
"Vitamin A, for example, is sort of opposite of B1 - the higher your A level, the leaner you are and vice-versa ("

retinol sets mitochondrial metabolic rate (thanks Tess);

Tucker Goodrich said...

"The obesity epidemic is more advanced in wheat-eating countries and countries with a high intake of processed carbohydrates, and less advanced in countries with a high intake of carbohydrate from polished rice."

Not any more.

"China Diabetes Rate Now Higher Than U.S."

As thiamine deficiency is common in China, I wonder if they've been supplementing, or if wealthier Chinese are eating better and getting more thiamine?

Or is it just the rest of the diet has gotten more "industrial"?

I've got a pretty severe gluten intolerance, and have avoided seed oils diligently after Guyenet scared the daylights out of me. :) I find the Chinese diet to be the very worst from my perspective, at least as practiced in American Chinese restaurants. I wind up eating steamed meat and vegetables when I go to Chinese restaurants, which, as you might imagine, isn't very often any more.

(I don't think wheat protein is a cause of diabetes, but I do think that linoleic acid contributes, I should clarify. Chinese food seems to contain cheap seed oils as a matter of course, whereas the traditional Chinese fat was port fat.)

Puddleg said...

Rice only grows in Southern China and in the North wheat is more commonly consumed.
I agree that linoleic acid added to a high-carb diet is probably what turns the tide. Gutter oil and industrial pollution may make their own contributions.
If there is a permissive effect of thiamin on weight gain (and if diabetes in China is accompanied by obesity to the extent it is in the USA, which may not be the case at all), then eating better - i.e. being able to afford more meat (pork meat is a good source of thiamin) or dairy may oblige.

James said...

"In most western countries white flour is fortified with vitamins including thiamine"

Actually, that's not true. Most EU countries do not fortify their white flour. In fact, other than the US, Canada, New Zealand and Australia, fortification is almostly entirely limited to developing nations and third-world countries who very much have vitamin deficiencies.

To be honest, I think this only solidifies your point. The most obese countries are the ones that seem to do the most food fortifications and have access to and get vitamins from other sources (multivitamins, variety of foods).

"Carbohydrate restriction, on the other hand, is a practical way out of any dilemma, as...fattening carbohydrates is reduced"

I have to disagree. The evidence you've presented here shows that it's likely the fortification of carbohydrates, rather than the carbohydrates themselves, that is likely responsible for obesity.

It's easy to forget, but the most illustrative example of this is France. France does not fortify any of its foods or flour, but they consume nearly twice as much wheat as Americans do!

Yet the French are quite healthy, have a very long life expectancy, and they have about 1/3 the obesity that Americans do. They are known for being slender. They've been eating this way for centuries—with patisseries, boulangeries and chocolatiers on practically every corner and hardly any need for gluten—free options. Gluten-free bakeries are quite difficult to find in France.

So, If the French can eat twice as much (unfortified) wheat as Americans and be amongst the thinnest countries in the world (known as the "French Paradox") then this only solidifies the hypothesis that the government fortification is to blame.

James said...

Incidentally, iron fortification may also implicated in obesity, which would explain why the US and Britain have a much larger obesity problem, since they not only fortify with thiamin, but also with iron as well as niacin (niacin is implicated in the studies you reference).

Up until recently it was believed that billions of people have iron deficiency, and need iron pills or to eat more meat. However, it is now understood that the symptoms of iron deficiency are usually due to "anemia of chronic disease/inflammation," or "iron withholding," in which iron is withheld from microorganisms (and cancer cells) so they don't grow. Thus, iron absorption is lowered, and blood levels go down due to a hormone called hepcidin, which is induced in inflammation and stops iron from getting out of cells, including gut cells.

This means that iron overload can go together with anemia, and this is apparently what happens in obesity, which is an inflammatory disease.

People who are obese tend to have iron overload in the brain, in their urine and possibly in fat cells. Iron is actually only a problem when it's unopposed by manganese and manganese is also well known to promote blood sugar regulation. Even obligate carnivores obtain sufficient manganese—the stomach contents of their prey is often extremely rich in manganese. For instance. 100g of caribou stomach contents has 10mg of Manganese, which is roughly the Upper Limit in humans.

When food is fortified with iron, there is no manganese to oppose it. Eating a diet rich in meats and fortified carbohydrates would be a double-whammy—especially when you consider that saturated fat increases iron absorption and inhibits that of manganese.

The French eat a lot of chocolate (rich in manganese, iron and copper) which easily fortifies their high consumption of unfortified wheat. They are basically trading their wheat bran for cacao.

I believe you have stumbled on to some major correlations here. Government Food fortifications appear to be causing some major imbalances in populations, which correlate with obesity patterns. In the countries that don't take part, such as in France and other EU countries, we don't see nearly the level of obesity as fortified countries.

Congratulations. I believe you've apparently solved the French Paradox as well as a major contributor to the obesity problem!

Tucker Goodrich said...

""Carbohydrate restriction, on the other hand, is a practical way out of any dilemma, as...fattening carbohydrates is reduced"

"I have to disagree. The evidence you've presented here shows that it's likely the fortification of carbohydrates, rather than the carbohydrates themselves, that is likely responsible for obesity...."

The problem with this argument is that China has one of the biggest problems with obesity and diabetes—much worse than the US, and they're not on your list of fortifying nations.

The research I've seen from China indicates that diabetes is correlated with rice consumption...

Puddleg said...

In China today you have the problem of very poor quality seed oils being added to a diet high in rice; oils are most of the calorie increase associated with diabesity in developing countries.
If you wanted to fatten an animal you'd feed it starch, but if that didn't work you'd supplement its feed till you found the magic formula.
There might be some clues here in the chicken industry and the changing makeup of mash over the years.
Yudkin says (1985) that Asian countries are resistant to rice fortification.
James, anaemia of chronic disease - more people need to know about this! - non-heme iron added to foods isn't well-absorbed, so what does it do in the gut?
Unfortunately, I don't think the French are long-lived for Europeans. They have less CHD (even allowing for their idiosyncratic coding system) but more alcohol-related liver disease and stomach disease, which cancels out the CHD benefit. Interesting about the wheat though. I'v probably underestimated how many calories Americans get from corn.