The Origins of the High-Fat Hep C Diet

The other day I rediscovered one of my early posts about my concept of a high fat diet for Hep C.
It was posted on the Life Extension Foundation forum on 27 Feb 2011.

I started restricting carbs after reading "Protein Power" by Michael and Mary Eades, where the rationale for reducing inflammation by restricting carbs and eating more fats is spelled out.
This was good, but it wasn't till I read "Dr Atkin's New Diet Revolution" that I saw the link between what happens to VLDL/TG on ketogenic diets, and what HCV does to exploit lipids.
Next, I found out about the Nanji-French research that demostrates a liver-protective role for saturated fat, and tried limiting PUFA.
Then (about October 2010) I started to get the results I wanted and was ready to write about it, so I posted about it on MySpace (remember MySpace? Tom you bastard, I want my customized settings back!) then posted this at LEF (to date there have been no responses).

http://ask.lef.org/1620/Atkins-Paleo-Diet-for-treatment-of-Hepatitis-C?keywords=DIET&pageindex=1

the HCV virus
is linked exclusively to lipid metabolism (blood fats, commonly but
erroneously called "cholesterol").

- HCV virion is completed by enzyme DGAT, which also packages fats
(triglycerides) prepared by the liver.

- HCV virion escapes infected liver cells via VLDL-c expression.
VLDL-c (very low density lipoprotein cholesterol) carries fats made by
the liver to cells that need them, also carries cholesterol and
lecithins made by the liver.

- HCV virion enters uninfected liver cells via LDL-c receptor. LDL-c
is remains of VLDL-c after fats have been delivered. The fewer
triglycerides, the larger the VLDL-c and LDL-c, hence the fewer interactions there will be with receptors.

This is why HCV only infects the liver - only hepatocytes have all of
these enzymes and receptors.

Now, where do triglycerides and VLDL-c come from? Over half comes from
the carbohydrate in the modern high-carbohydrate diet, converted to
fats for storage or energy, and this half is not produced at all on
high-fat diets.
In other words, on a high-fat, very-low-carb diet, serum levels of
triglycerides (FAT = Fatty Acid Triglycerides) and VLDL-c are
approximately 50% of the levels seen on a low-fat diet.
This diet should automatically reduce the HCV viral load by a similar
amount and the reduction should continue over time. Because the LDL-c
receptor is upregulated on the high-fat diet, probably increasing
uptake of HCV (yet the LDL-c are larger, so there are even fewer of them) the effect is not quite as clear-cut as that, but the trend is definitely downward (we need someone with math skills to
design a mathematical model for this).
[note: I don't think today that the LDL-C receptor will be upregulated so much, if at all, if the diet is high in cholesterol and restricted in PUFA]
Further, on a high-fat diet there is also a very significant drop in
pro-inflammatory cytokines involved in liver fibrosis and autoimmunity
(which are connected to and driven by insulin) - see Volek et.al.
There are other benefits too: the food being nutrient dense puts less
work on the gut, and extracting energy from fats requires fewer
vitamins and minerals compared to carbohydrate metabolism. Oxidising a
long-chain saturated fat to ATP involves the same reaction over and
over, which is economical, whereas oxidising glucose involves a
different reaction at each step. This is why refined carbohydrates and
foods high in sugar and starch cause vitamin and mineral deficiencies,
while meat contains all the nutrients needed to process the fats it
contains.

Further, diets high in highly saturated fats such as coconut oil, palm oil, and beef tallow are able to reverse liver fibrosis (Mezey, also Nanji et.al.), while high-PUFA vegetable oils promote liver damage in inflammatory conditions. DHA and lecithin are exceptions to this rule.

The ideal diet for Hep C, according to this hypothesis (and borne out by my experience over the past year) is a diet rich in animal protein and animal fat, with some fish but mostly red meat and eggs, in which most carbs come from green, leafy vegetables. Coconut and coconut cream are used with fish, and grains are completely avoided, as are all sugars except dark honey, fruit juice except small amounts of pomegranate, legumes are restricted to small infrequent servings, all potato is replaced with small servings of sweet potato and pumpkin. Food that needs fat is cooked in beef tallow or butter. Cold pressed virgin olive oil and sm all amounts of sesame seed oil are the only liquid oils used. Nuts and seeds are eaten occasionally. Berries are the main fruit, with small amounts of apple, mango, and apricot  [I have no idea now why these particular fruits were my exceptions to the no-fructose rule. Today I'd prefer citrus, and the occasional banana]. Spices are used often; cheese and yoghurt are preffered to milk and milk solids.

As for the objection that this diet may elevate cholesterol, high cholesterol levels in Hep C are associated with less fibrosis and a better response to interferon-ribavirin. This is a diet that elevates HDL-c and lowers triglycerides, which are better proxy markers than cholesterol alone.

Antioxidant supplements including Co-Q10, selenium, tocopherols, zinc, ascorbate, grape seed extract, plus krill oil or cod liver oil and vitamin D3 are taken.

Also, supplements supplying 400mg calcium and 150mg magnesium are taken with each meal of meat or high-iron vegetables to significantly reduce iron uptake.

Glucosamine and niacinamide, plus B12 and folate are used to promote normal iron metabolism and erythropoesis if necessary.

This hypothesis first published (c) 2010 by George D. Henderson, Huia, Auckland, New Zealand 

While looking for this, I also found the Atkins website recommendations for Hepatitis. These are pretty much the supplements I used to take, some of which I still use.
FYI, here is my current supplement regime:

100mg co-enzyme Q10

120mg Enzogenol pine bark extract (or 200mg grape seed extract) 

4mg astaxanthin

Lactobaccilus rhamnosus and bifidus probiotic

Magnesium (as CMD) with salt

Vitamin D (10,000 iu 2x weekly)

Vitamin K2 (MK7) 90mcg daily

vitamin E 130iu (in above supps, or I probably wouldn't bother)

vitamin C 60mg (ditto, but I'd take 500mg 2x daily if I had it)

I also eat some brazil nuts every day for extra selenium, and eat liver regularly for retinol, copper, etc.

What do I do in my spare time? This.

Thanks for reading this blog so patiently and critically, now it's time to relax and enjoy a song: "Secret Holiday" by The Puddle.  http://thepuddle.bandcamp.com/releases

Recent Blood tests: HCV Genotype 3 and Cholesterol

Some results of recent blood testing from Auckland Hospital. Getting enough blood to run the tests was, as always, difficult, but at least was possible on this occasion. It’s worth mentioning this because anything I report about my status should be seen in context. I’m 54 years old, I’ve been diagnosed HCV+ since 1991 (this was the first year testing became available here, I likely was infected much earlier), I was an IVDU, polydrug user from the 1980s till well into this century, an alcoholic and solvent abuser as well for much of the last. I gave up methadone, my last drug of addiction, about a year ago.

My fibroscan (elastography) result was 6.8. This is very light scarring (healthy livers go up to 5, cirrhosis starts at 12).

My ALT is 67 U/L; all the other LFT scores are normal (WNL).
Albumin is 52; this is the maximum normal, and I think a pretty reliable sign of a functioning liver.

Iron saturation was high at 0.55, and ferritin high at 251. This is definitely something I’ll be looking at. However, I don’t have the signs of inflammation that I used to attribute in part to high iron. I'm fit, sleeping well, and pain-free.

Hemoglobin was 154 g/L. MCV and MCH were maximum normal.
WBC count was low at 3.86 (4.0-11.0 is normal). Individual WBC counts were all low but WNL.
This is interesting because I haven’t had any infections all year (it’s almost spring) beyond one light cold. Are my WBCs low because some other aspect of innate immunity is taking care of business? Because my diet is low in allergens, pathogens and toxins, and the probiotics I take are working?

IgG was 14.3, IgM 0.89, both WNL.
Platelets were WNL at 237, haemostatis PR = 0.9, HbA1c = 36
Negative for coeliac markers, but then I never touch grains, so I would be.
Vitamin B12 = 495 pmol/L (ref. 170-800)
Folate = 28 nmol/L (ref. 9-45)

HIV negative, HBV antibody positive, HBs Ag negative. As I haven’t had an HBV vaccine, this means I’ve been exposed to hepatitis B and cleared it at some stage. I’m pretty sure I know when that was; everyone else in that room got sick. 

The most interesting news for me; my HCV genotype is 3. If you’re wondering why it took so long to find this out, you don’t understand the New Zealand health service. 

HCV Genotype 3 and Cholesterol.

Genotype 3 is the form of HCV most specifically associated with fatty liver (steatosis) and hypocholesterolaemia. Steatosis can be a negative factor in any case of HCV infection but in G3 it is promoted by viral mechanisms as well as host dietary factors. One of the mechanisms is the suppression of distal sterol synthesis beyond the proto-sterol lanosterol.

HCV G3, but not G2, selectively interferes with the late cholesterol synthesis pathway, evidenced by lower distal sterol metabolites and preserved lanosterol levels. This distal interference resolves with SVR. Normal lanosterol levels provide a signal for the continued proteolysis of 3-hydroxyl-3-methylglutaryl coenzyme A reductase, which may undermine other host responses to increase cholesterol synthesis. These data may provide a hypothesis to explain why hypocholesterolemia persists in chronic HCV infection, particularly in HCV G3, and is not overcome by host cholesterol compensatory mechanisms.http://www.ncbi.nlm.nih.gov/pubmed/22318926


 G3 wants HMG-CoA reductase to keep ticking over; as completed cholesterol accumulates it suppresses HMG-CoA reductase. By lowering conversion of lanosterol to cholesterol, the virus keeps the enzyme active – and cholesterol low. 

(The reduction in cholesterol - distal sterol - synthesis seems to be achieved by lowering expression of the cytochromes CYP51 and CYP11A - see table II).

Without the cholesterol, fats can’t leave the cells of the liver easily. They stay there till the virus is completed and ride out whenever triglycerides (and the HCV virions) are released as VLDL. This should mean a relatively high TG/LDL ratio. 

There's another benefit to the virus, perhaps the main one; with serum cholesterol levels low, LDL-receptors are increased to compensate, and the LDL-receptors mediate the entry of HCV virions into uninfected cells. 
Less cholesterol equals more LDL-R; more LDL-R equals greater ease of entry for HCV.
This is why we should limit PUFA (cut out vegetable oils), this plus the damage from the oxidation of highly polyunsaturated membrane lipids. Animal PUFAs - AA, DHA, EPA - have antiviral benefits and we want to be eating these, but probably not supplementing them that much (Krill oil is better than fish oil).

Put another way, the viral strategy is to corner the market in cholesterol and restrict the supply. This increases demand in uninfected cells, increasing their exposure to the virus, which enters using LDLR associated receptors like CD81 and NPC1L-1.

What happens if you just eat a lot of eggs? The cholesterol from the diet suppresses HMG-CoA reductase (http://www.lipidworld.com/content/6/1/34/), as well as eventually decreasing LDL-R expression (http://ajcn.nutrition.org/content/39/3/360). The viral strategy is stymied from both ends.

Not everyone with HCV G3 develops steatosis or hypocholesterolaemia. Could the difference be something as simple as having adequate cholesterol in the diet and limiting carbohydrate? 

Higher LDL is a good indication that someone with HCV will respond to antiviral drugs, and is associated with lower rates of fibrosis.
However, clinical experience (thanks, Silvia) is that high LDL doesn’t always mean good response, low LDL doesn’t always mean non-response.

It’s worth remembering that a crappy diet of cake and biscuits can elevate LDL (at least, it usually does this in people without HCV) as surely as a good grain-free diet of eggs, meat and vegetables. We’re not really talking about the same phenomenon at all. Just as, in physics, the phenomenon we call weight can be produced by gravity (on the surface of the earth) or by acceleration (in a centrifuge or rocket), and its meaning and implications may be quite different. Shooting across space in an accelerating rocket ship may well have different long-term consequences compared to standing on the Earth’s surface, even if both sets of scales are reading the same weight at present.

Think about it: saturated fat supposedly elevates serum cholesterol, which is a risk factor for heart disease (I tried to find a scientific reference for this simple statement, without added nuances about particle size, ApoE, and BMI, but it has proved surprisingly difficult. However, most governments, and quite a few doctors, still say it; for example, the Australians here: http://www.aihw.gov.au/high-blood-cholesterol/). 
Increasing consumption of saturated fats doesn't correlate with CVD risk, but obesity does.
So either fat doesn't make you fat (which is the case in some scenarios, but surely not all), or something else that also makes you fat gives you heart disease.

My GP is still encouraging me to lower my cholesterol, and the hospital didn’t take a reading. Me, I feel thankful it’s still “a bit high”. If I was in the cholesterol range that the NZ government thinks is optimal, I’d start to get a bit worried.


One size fits all? Wasn’t there a chap called Procrustes once who believed that? Whatever became of him?


Appendix:

Current lipid panel (fasting): mmol/L converted to (mg/dL). Ok, only when the frickin' HTML will allow it. Note how no reading except HDL can be "too low". 

Total Cholesterol:  6.7  H     
Triglyceride:          0.8         
HDL:                     1.63              (63.57)
LDL (calc.)            4.7   H    
Chol/HDL ratio:     4.1          

HCV viral load on this day (21st May 2012): 60,690 IU/mL (4.78 log)



Lipid panel from 07 Feb 2012, during ketogenic diet phase:

Total Cholesterol: 8.9   HH  (347.1)
Triglyceride:         1.3          (115.7)
HDL:                    1.65         (64.35)
LDL (calc):           6.7    H    (261.3)
Chol/HDL ratio:     5.4   H

HCV viral load on this day: 25,704 IU/mL (4.41 log)

"Total blood cholesterol levels above 5.5 mmol/L are an indication 

of a greatly increased risk of developing coronary heart disease. 

Levels above 6.5 mmol/L are considered to indicate extremely high

risk.". 

5.5 mmol/L = 214.5 mg/dL, 6.5 mmol/L = 263.5 mg/dL.

This is interesting: http://renegadewellness.files.wordpress.com/2011/02/cholesterol-mortality-chart.pdf

And this:

"In 1987, in the Journal of the American Medical Association Framingham Study investigators reported these two important findings: 1) Over age 50 there is no increased overall mortality with either high or low serum cholesterol levels, and 2) In people with a falling cholesterol level (over the first 14 years of the study), for each 1% mg/dl drop in cholesterol there was an 11 percent increase in all-cause mortality over the next 18 years. (JAMA 1987;257:2176-2180)"

Hey, I'm over age 50! Better keep my cholesterol up.

More on the adverse consequences of low cholesterol from Chris Masterjohn.

It gets worse: 

"There were 27 deaths due to suicide. Adjusting for age and sex, we found that those in the lowest quartile of serum total cholesterol concentration (less than 4.27 mmol/liter) had more than six times the risk of committing suicide (rate ratio = 6.39; 95% confidence interval = 1.27-32.1) as did subjects in the highest quartile (over 5.77 mmol/liter). Increased rate ratios of 2.95 and 1.94 were observed for the second and third quartiles, respectively. The effect persisted after the exclusion from the analysis of the first 5 years of follow-up and after the removal of those who were unemployed or who had been treated for depression. These data indicate that low serum total cholesterol level is associated with an increased risk of suicide."

Zoe Harcombe lists the conflicts of interests of the scientists who set UK cholesterol guidelines; every single one of them receives money from companies that market "cholesterol lowering" statin drugs. Hmmn.

Well I guess they can always start prescribing antidepressants once they get your cholesterol down.

Viral Manipulation of Host Behaviour by HCV?

It's well known that some viruses and other parasites can influence host behaviour and physiology to maximize their spread.
Respiratory viruses make you cough and sneeze. Rabies makes you aggressive (it is spread by biting) and hydrophobic (dehydration concentrates the virus in your saliva). Toxoplasmosis replaces a mouse's instinctive  fear of cats with an attraction to them (Toxo has a two-phase, mouse-cat-mouse life cycle).
A blood borne virus like HCV falls somewhere between a 'flu virus and rabies in its ease of spread. It relies mainly on injections and transfusions, being dependent on blood to blood transmission.
What adaptations and manipulations of host physiology and behaviour would promote the spread of a virus that can today only be spread effectively by licit and illicit medical procedures?

Dysphoria comes to mind. Feelings of depression and pain for no good reason; slow recovery from other insults, bad hangovers from alcohol that cannot be relieved by more alcohol. Hypochondria that exposes one to both medical procedures (means of transmission in past decades, and in 3rd world nations today) and to oral medications that can decrease ones sense of caution. Tending to lead to, and reinforce, less hygiene and more sharing among addicts. Poverty that makes blood donation a necessity (a good means of spread in past decades).
In the modern world, a blood-borne disease that makes you feel bad in every way, but leaves you well enough to find a means to ease this temporarily, has a good chance of moving from host to host. The after-effects of the drug-seeking behaviour itself will soon perpetuate the state that benefits the virus.

Interestingly, some nutriceuticals that ease HCV pathology have also been shown to decrease drug seeking behaviour and related pathologies:

NAC prevents cocaine relapse:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661026/

Glutamate and compulsion in addictions:
http://psychiatryonline.org/article.aspx?articleid=17769

Acetyl-carnitine in methadone withdrawal (ALCAR is a GABA agonist)
http://journals.lww.com/clinicalneuropharm/Abstract/2009/01000/Acetyl_L_Carnitine_in_the_Management_of_Pain.8.aspx

Milk Thistle as effective as fluoxetine for OCD:
http://www.naturafoundation.co.uk/?objectID=4031&page=1

Niacinamide/nicotinamide a GABA (or benzodiazepine) receptor enhancer:
http://www.sciencedirect.com/science/article/pii/0091305780902361


NAC reduces cannabis use:
http://ajp.psychiatryonline.org/article.aspx?articleid=1184217

Does the virus modulate behaviour?  Does it need to? And did it do so differently in its evolutionary past?
Before the 20th century, medicine was of less use to blood-borne viruses like HCV. (see the second part of this article, HCV and the History of the Human Race). Warfare would have been a better way to get out and about, to jump from one tribal group or one city-state to another.
Could a virus make us more aggressive or xenophobic?
Would it need to? Or were we already warlike enough to make the perfect host?

Footnotes in Support of the Thiamine Hypothesis of Obesity

Some footnotes in support of the Thiamine Hypothesis:

From The Penguin Encyclopaedia of Nutrition, by John Yudkin:

"The reduction in the prevalence of beri-beri in some countries, such as Japan, has come about by a general improvement in living standards, which as always has been accompanied by a reduced proportion of cereal in the diet, and an increased proportion of other foods. In addition, some governments have introduced legislation requiring a lesser degree of milling of the rice, but this is not always enforced, and the people still prefer the whiter polished rice they have been used to. Nor has there been much success in persuading people to parboil rice if they have not traditionally used it in this form. The addition of thiamine to rice has also been attempted by some countries, but this too is difficult to enforce in the poorer countries.

[The imported rice which we buy in New Zealand is not fortified, and vitamins are sprayed on fortified rice and easily lost in washing and cooking. Only in the USA and Canada does the fortification of rice appear to be, though not mandatory, very pervasive] 

Although beri-beri is usually found in people whose staple food is polished rice, it does occur, although rarely, in other circumstances. It has been seen, for example, in areas where there has been a high dependence on bread made with highly-milled and unfortified wheat flour."

From Principles of Biochemistry 1954 (1973 edition)

"The sparing action of lipid was thought to reflect a lesser metabolic demand for thiamine, but since the thiamine pyrophosphate (TPP) content of the tissues of animals fed a high-lipid diet is considerably higher than that of animals on a high-carbohydrate diet, the lipid may in some manner protect thiamine from destruction.

Nutritional surveys indicate that for much of the American population the thiamine intake is marginal; few adults consume more than 0.8 mg/day, and many eat appreciably less. Thiamine intake can be augmented relatively cheaply by increased use of peas, beans, and enriched or whole-wheat bread, as well as by improved cooking practices. Prolonged cooking of peas and beans with soda results in destruction of as much as 60% of the original thiamine content, and excessive cooking leaches the water-soluble thiamine from many foodstuffs."

In a 1994-1995 survey, the mean intake of thiamine by American adults had more than doubled, to about 2 mg/day, with the lowest percentile near the older figure of 0.8 mg/day, and the highest at around 4 mg/day (this was from food alone, vitamin supplements were not included; today, energy drinks, vitamin enriched chewing gum, and vitamin water would also be boosting the intake): http://www.nap.edu/openbook.php?record_id=6015&page=466

Conclusion:

There is a difference in thiamine status between East and West, and a difference between the Western past, even the recent past, and the Western present, which is consistent with optimal thiamine status being a factor in the "obesity epidemic".
Marginal thiamine status has the potential to be an important confounder when evaluating associations between the proportional carbohydrate content of different diets and obesity rates.

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

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.
http://medical-dictionary.thefreedictionary.com/Thiamine+deficiency

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:

http://www.medsafe.govt.nz/profs/datasheet/a/Apo-BComplextab.pdf

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). http://www.ncbi.nlm.nih.gov/pubmed/21126339  

In this paper, obese individuals store and recycle thiamine more than controls. http://www.ncbi.nlm.nih.gov/pubmed/15098017

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: http://www.jbc.org/content/206/2/725.full.pdf

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.
http://pubs.niaaa.nih.gov/publications/arh27-2/134-142.htm

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.

http://lpi.oregonstate.edu/infocenter/vitamins/thiamin/

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).

http://helid.digicollection.org/en/d/Js2900e/8.2.html

Why Might Statins Cause Memory Loss and Arterial Calcification? Vitamin K2, and HMG-CoA Reductase

In a recent trial of statin use in diabetes, greater compliance was associated with coronary calcium progression.
Statin doctors were quick to discount the findings. But aren't statins supposed to stop atherosclerosis? In this case, whether or not the statins caused the problem, they certainly didn't prevent it.
Is there a mechanism whereby statins may increase calcium deposits in arteries?
Let's look first at another side effect of statins; "certain cognitive effects such as memory loss and confusion".


Is there one effect of statins that could account for both these results?


Statins are HMG-CoA reductase inhibitors. HMG-CoA reductase is the rate-limiting enzyme for cholesterol synthesis. Cholesterol, like most lipophilic hormones and vitamins, is a terpene derivative, or isoprenoid.
Some of the essential isoprenoid structures, such as those found in vitamins E and A, are formed in plants, but others, including Co-enzyme Q10 (ubiqionone) are formed in the cytosol from a product of the HMG-CoA reductase pathway, mevalonate.
That statins can lower ubiquinone levels is well-known and accounts for occasional serious adverse reactions.
However, ubiquinone and cholesterol are not the only HMG-CoA reductase dependent compounds essential for health.


a) ubiquinone
b) menaquinone
the repeating isoprene group derived via HMG-CoA reductase is bracketed.


Vitamin K is present in green vegetables and vegetable oils as phyloquinone, and in fatty animal foods as menaquinone-4 (MK4), while bacteria produce menaquinone-7 (MK7).
Vitamin K1 is converted to vitamin K2 by removal of the phytyl side-chain and replacement with an isoprenoid side-chain.  
When this occurs in the brain the MK4 produced is an essential co-enzyme for the synthesis of special sulfur-containing lipids called sulfatides. Low CNS sulfatide levels are associated with congnitive decline and seen in the early stages of Alzheimer's disease.

Low sulfatide content in brain myelin has been recently linked with the disruption of myelin integrity [14, 21], whereas the disruption of myelin integrity was implicated as an essential contributor to cognitive deficit [6, 7, 43, 44]. Although our findings of dietary-associated decreases in myelin sulfatides suggest a potential disruption in myelin integrity in evaluated brain regions, it is currently unknown whether such disruption would be sufficient to modify motor and cognitive functions controlled by these brain regions.

In the present study both dietary forms of vitamin K1 were converted to menaquinone-4 (MK-4) in the brain. 

Doug Bremner states that congnitive impairment is more commonly reported with the more lipid-soluble statins, such as Zocor (simvastatin) and Lipitor (atorvastatin), which cross the blood-brain barrier, and is rarer (but still seen) with water-soluble statins such as Pravachol (pravastatin).


Vitamin K2 as menaquinone-4 (MK4) also prevents arterial calcification. 


 Warfarin-treated rats were fed diets containing K1, MK-4, or both. Both K1 and MK-4 are cofactors for the endoplasmic reticulum enzyme γ-glutamyl carboxylase but have a structurally different aliphatic side chain. Despite their similar in vitro cofactor activity we show that MK-4 and not K1 inhibits warfarin-induced arterial calcification.


Chris Masterjohn has long been writing about the importance of vitamin K2 on his blog at Weston A. Price.


Thus there may be a common mechanism for both calcification and memory loss; decreased conversion of vitamin K1 to MK4.


Now it may be that a diet high in animal fat and fermented dairy products will supply all the MK4 you need. But is a person being prescribed statins to lower cholesterol going to be advised to consume such a diet? 
Only if the doctor knows that the saturated fat lipid hypothesis is nonsense (the sugar-and-starch lipid hypothesis is another matter entirely).


An article postulating that statins might affect bone density by lowering K2 synthesis was published by Linda L. Demer in the journal Arteriosclerosis, Thrombosis, and Vascular Biology in 2001.