Saturday, January 24, 2009

The Tokelau Island Migrant Study: Gout

Gout is a disorder in which uric acid crystals form in the joints, causing intense pain. The body forms uric acid as a by-product of purine metabolism. Purines are a building block of DNA, among other things. Uric acid is normally excreted into the urine, hence the name.

On Tokelau between 1971 and 1982, gout prevalence fell slightly. In migrants to New Zealand, gout prevalence began at the same level as on Tokelau but increased rapidly over the same time period. Here are the prevalence data for men, from Migration and Health in a Small Society: the Case of Tokelau (I don't have data for women):

This paper found that the age-standardized risk of developing gout was 9 times higher in New Zealand than on Tokelau for men, and 2.7 times higher for women.

The Tokelau Island Migrant Study: Background and Overview
The Tokelau Island Migrant Study: Dental Health
The Tokelau Island Migrant Study: Cholesterol and Cardiovascular Health
The Tokelau Island Migrant Study: Weight Gain
The Tokelau Island Migrant Study: Diabetes
The Tokelau Island Migrant Study: Asthma

35 comments:

Anonymous said...

Gout is seasonal:

http://www.ncbi.nlm.nih.gov/pubmed/9489831

http://www.ncbi.nlm.nih.gov/pubmed/10534553

It peaks in the spring, when vitamin D levels will most likely be lowest.

Gout could be related to vitamin D deficiency due to less sun exposure and/or less vitamin D in the diet.

TedHutchinson said...

Circulating Vitamin D3 and 25-hydroxyvitamin D in Humans:
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17218096

Hollis explains here how the vitamin D-25-hydroxylase operates well below its Vmax because of chronic substrate (vitamin D) deficiency.

We find Decreased serum concentrations of 1,25(OH)2-Vitamin D3 in patients with gout
http://cat.inist.fr/?aModele=afficheN&cpsidt=2180690

Possible the further from the equator the more likely one is to have less Calcitriol or Calcitriol limited by lack of substrate.

Robert Andrew Brown said...
This comment has been removed by the author.
Robert Andrew Brown said...

Onenatural

Thanks interesting.


Fructose and uric acid.

A causal role for uric acid in fructose-induced metabolic syndrome

http://ajprenal.physiology.org/cgi/content/full/290/3/F625


Visceral fat apparently increases the risk.

http://www.ncbi.nlm.nih.gov/pubmed/9711987?dopt=Abstract


Carbs and Omega 6 - are they factors?

From memory Omega 6 promotes visceral fat storage and I have seen several suggestions carbs increases visceral fats.

Stephan from memory previously posted the rat? trial in which removal of visceral fat improved inflammatory related condition.

Stephan do you know the comparative body fat status of the two groups ?


Robert Brown

Author Omega Six The Devils Fat

www.omegasixthedevilsfat.com

theoddbod said...

how have their exercise/activity levels changed or have they?

Stephan Guyenet said...

Onenatural and Ted,

I think vitamin D is a logical possibility.

Robert,

Both the Tokelauans and the migrants gained weight, but the migrants gained more.

Theoddbod,

They didn't measure exercise quantitatively, but here's what the authors observed anecdotally. Men on Tokelau exercised less at the end of the study than at the beginning. Women exercised about the same. Migrants exercised more than non-migrants on average.

Sel said...

Gout and kidney stones: any correlation? Is there a causal link between sugar and kidney stones - large uric acid crystal often form the nucleus of the most common stones according to some studies. I wonder how the body's inflammatory response figures into the making of a kidney stone? Are there any links between blood sugar levels and if the body perceives itself as being dehydrated?

Sel said...

I must say that I followed the Atkins Diet for almost a year. As it was written in the late 1990s it was unbalanced, no nuance at all and seemed to promote his line of supplements to make up for what you weren't getting. I enjoyed it and lost weight. But, according to my nephrologist and urologist, the size of my kidney stone in 2005 would have taken 5 to 7 years to grow to the size it was (how do they really know this?) and the time frame for the beginning of the stone was about the time I was on Atkins. Purines and meat rich in said purines....I must wonder if I didn't do it to myself?

Aaron Blaisdell said...

I haven't looked into the scientific or medical evidence for the link between meat consumption and kidney stones, but given the touted relationship I'd like to add the following hypothesis: Gout and kidney stones could result in part from a combination of increased intake of meat and other animal-derived protein on the one hand and insufficient intake of Vitamin D on the other. Obviously, with all of the hypotheses mentioned, we need some good empirical tests to discriminate among them. But given the critical role of Vitamin D (and K2) in processing of Vitamin A that Stephen has documented in numerous blogs, a Paleolithic diet could have its hazards in combination with low levels of Vitamin D.

Robert M. said...

Taubes basically flat out says that the primary reason the nutritional scientists ignored Atkins in the 1970s was because he was a pompous ass. Given the outsized egos scientists often have, he must have been a real jerk, or the nutritionists were unusually thin-skinned.

On the protein->urea front, does the text mention how much coffee and tea the islanders and migrants drank? I wonder if the migrants were perpetually dehydrated.

Stephan Guyenet said...

Sel,

There is an association between sugar consumption and kidney stones, but I don't know if they've established causality.

The other potential factor is vitamin K2. It activates a protein that prevents the precipitation of calcium salts in urine. Reference

Vitamin D also increases the synthesis of that protein.

Aaron,

I'm certainly willing to believe it's multi-factorial. It's possible that lots of purine-rich foods could aggravate the problem even if it's caused by something else. But I haven't found any evidence to support that at this point.

Robert,

Roughly 1/3 of people drank tea on Tokelau whereas over 3/4 of people drank either coffee or tea in NZ.

Pasi said...

Gout correlates with visceral fat which correlates with liver fat which is related to metabolic syndrome and T2DM and of course CHD.

One interesting thing that I recently found out was this:

"Aspirin (and other salicylates) have varying effects on uric acid. At low aspirin levels (as may occur in persons taking aspirin only occasionally), aspirin can increase blood uric acid."

http://www.ncbi.nlm.nih.gov/pubmed/10643705

http://cat.inist.fr/?aModele=afficheN&cpsidt=18227907

Minidose aspirin for T2DM patient..hmmm...

Unknown said...

Stephan you had linked some nice in depth reference previously about kidney stones but it wasn't what you linked here. Do you still have that page? I can't find the ref. Is the study you linked here new information since that other page?

Many thanks for the help.

Stephan Guyenet said...

Erin,

Was it this?

James said...

Keep going guys. This is beginning to get interesting. If I am not mistaken we're seeing something developing here.
Anecdotal: I just learned about an acquaintance who developed heart problems, ended up in the hospital. The works, got a couple of stents and is recouperating. Here comes the interesting part. Wanted to slowly get going but had to stay put for a bit longer because of a severe attack of
gout(!).
The guy is not overweight, not overly active, but neither a couch potato, however the studious type.
Fructose, simple carbs.. uric acid.
thanks for the link Robert. I am almost having an Aha-Erlebnis.
Ever since Stephan brought up his Tokelau information, combined with the studies accessed through Weston Price ( Uffe Ravnskov, the Swiss, and others)I think we're moving in the right direction with being very suspicious of some of our mainstays (carbs)in certain forms

Carl said...

FYI, I found this WEB page listing purines.

http://www.acumedico.com/purine.htm

Venkat said...

Stephan,

I am a male, 38 years, Type II diabetic. I follow low carb diet ( ~40g of carbs).

While my A1c is at 5.0, Uric Acid jumped from 5.9 to 8. My Vitamin D level is 30. Only one difference between last time lab work and this time is - I have started taking Fish (Anchovies) oil capsules for Omega 3.

Any idea to reduce the uric acid levels?

Thanks

Venkat

Stephan Guyenet said...

Venkat,

Reducing sugar (fructose) intake and keeping your vitamin D level high are strategies to consider. I don't know anything about the relationship between fish oil and uric acid.

Terry Hilsberg said...

Stephan,

At the end of this post you noted that the fructose consumption data etc. did not explain the difference in incidence of gout between the Toeklau person resident on their home island or in NZ

I noticed recently that none of the responses to your post identified alcohol consumption as a possible difference between the lifestyle of the folks on their native island and in New Zealand.

It was my understanding that serious alcohol consumption basically has the same impact as serious fructose consumption on the production of uric acid (and a bunch of other MS indicators). e.g Feig et al, Uric Acid and Cardiovascular risk, NEJM, Oct 23, 2008.

I speculate that this may be an explanation. It is my anecdotal understanding that alcohol consumption dramatically increased in these island populations as they moved to NZ.

As an aside, whilst I find much of the fructose as a cause or precursor of MS, literature convincing, I also wonder about the impact of the combination of increased frucotse and alcohol consumption.

John Paolo said...

Wow, this is a good discussion. I've never seen it in any literature, but I've always thought that gout was also related to weight issues. The people I personally know that have gout are also overweight. That would be great to know. Perhaps it's just an overdue diet that is preventing me from getting rid of the pain.

Anonymous said...

My mother is tiny but has had several attacks of gout. Metabolic Syndrome and diabetes are endemic in her side of the family but previously the only symptom she had was high blood pressure (for about 50 years), and high but "not diabetic yet" glucose from steroids.

I was pointed to this list of purines

http://www.britishdalmatianclub.org.uk/downloads/Purine%20Table%202003.htm

apparently dalmations have a genetic failure to correctly process purines. Though I have to wonder about owners who would feed them endive.

Her attacks appear to have been caused by rhubarb. There's that fructose again, and also oxalate.

I've had it a couple of times, only in one thumb but that was painful enough: I don't know what was causal except almost certainly the high BG I didn't know I had then. It's one of many conditions "associated" with Type 2, like frozen shoulder, carpal tunnel etc. where connective tissue is glycated, so my money's on glycation as one of several factors.

Dr. Curmudgeon Gee said...

Hi, Stephen,

thanks for the interesting article.

my mom also has gout.
her trigger food seems to be chicken soup.

FYI: she is a little overweight & slightly elevated blood pressure. she exercises lightly.

yes, she was told to cut down food that is purine rich.

as a result, she eats a very "healthful" diet (by the modern standard): (white) rice & vegitable with little meat, low fat. she does not eat much no junk food.

since recently i have been rethinking about nutritian & diet,

so it dawned on me that maybe i should tell her to eat less rice?

regards,

pam

Anonymous said...

Could it also be something to do with the homogenised milk consumption of the subjects?
I think I remember something to do with xanthine oxidase (an enzyme is milk) helps to breakdown purines.

Unknown said...

I am 31 years old, a little over weight and have uric acid level 11. Recently my vitamin d level has been tested as 18.4. I take low purine diet and does some excerise, but i used to get gout trigges once a while from my child hood. I was very active in my childhood playing soccer etc and sweat a lot. When i sweat i can see salt formation on my shirt. Recently i read about Fanconi Syndrome in which Kidney malfunction and excretes minerals and salts which will lead blood acidic. Does this low level of vitamin D and high level of uric acid has any relation to Fanconi Syndrome. But all the other contents in my blood are normal. None of the doctors i have consulted couldn't find the root cause of this issue.

Sarah said...

I think there are some interesting things going on within those fat storage cells. Fasting can also trigger a gout attack. When the body stops using immediately ingested food and starts using up it's stores of energy from fat cells. Are they also storing powerful potential to raise uric acid in the blood?

I've been on a low-carb diet to reduce my own fat stores and protein/fat play a role there also, shifting metabolism to use those fat stores. Is the same mechanism that reduces my fat stores when eating protein/fat also the same that triggers gout attacks in those that are more susceptible? That might be what is leading people to believe that eating protein would trigger a gout attack. Maybe the fat stores should be investigated as to what they are actually storing.

Is there such a study?

Sarah said...

A couple of other thoughts.
Have the various kinds of food marketing influenced the diets of each group? Farmer's market vs supermarket, for example? Availability of junk food, sugar and high carbohydrate foods on a daily basis?
I've also observed a connection with the use of MSG and sudden increase in Uric acid in some individuals. Has this been studied? MSG comes in many prepared foods. Could the influence of prepared foods also be a factor to consider when comparing the two groups?

Also what time of the year are the samples being taken, there might be some clues there. With Vit D in question, are there differences in the aftermath of rainy vs sunny seasons? Outside work vs indoor work during the daylight hours?

How about daily alcohol consumers vs weekend binge consumers?

I would think more influences might be found in the basics like water, diet, how and when consumed. Have the emigrants changed their eating habits?

Are extreme low and high fluctuations in blood sugar and/or pH levels to blame for gout problems?

Bunpoh said...

Sarah - my husband and I have been using rounds of the HCG diet with real HCG provided by our doctor to lose weight. Gout runs in my husband's family. Almost invariably this has produced a massive gout attack in my husband during the first few days, EXCEPT this last time. If you aren't aware, HCG is a pregnancy hormone, which in conjunction with a very restricted diet causes rapid fat loss and a fat-burning metabolism. So you may be on to something. The doctor who first did the 30 years of research developing the diet did mention that people susceptible to gout will almost invariably develop it within days of starting a round, and should take preventative measures.

I wonder if his lack of gout this time has been because he has been supplementing with Vitamin D up until the beginning of the diet? Or, possibly because this time he is losing weight that he had previously lost, but regained recently, and not enough of the substances that produce gout were stored in the fat cells? I'm fascinated by this as well, and relieved for him.

Sarah said...

That Might lead to an answer for the main Discussion Question. The NZ bunch went on more diets than the Tokelauans or caught the flu more often thus ended up fasting more.

Turns out all kinds of molecules and food stuffs are stored in fat cells.

I have already suggested to my husband that before he loses weight, he should up the D3 and be on gout medication. I think there are too many people on gout meds that don't take advantage of getting down to their ideal weight before tapering off the meds. If just enough vit D3 would prevent an attack, that would be good news!

This seems to be the time of year in the northern hemisphere for gout attacks, lack of strong sunshine and wanting to take off holiday weight plus flu season tends to be a nasty combination.

telemachos said...

Okay, take two--but it's ridiculous that I just had to jump through hoops to get a google password and that, at the end of that process, my comment was lost and I have to write it all over again. Come on guys--this is the year 2011. We shouldn't still be having to go through this nonsense.

Okay--I've got gout, and becoming virtually vegetarian has caused gout attacks to go away. But becoming vegetarian permanently is not an option for me. My thinking has been pretty much along Weston Price Association lines, although I do not eschew sugar as consistently as I should, and my logical reasoning about gout is the same as yours. So what else to do?

Recently I spent a few months in Laos and I had horrible gout attacks. Since Lao cooking uses fermented fish in everything, it could be that these purine-rich foods are indeed the cause. Furthermore, since I was getting loads of sun in Laos, it is hardly likely that I lacked vitamin D.

But here's another element--I was suffering grievously from some intestinal parasites I'd picked up; they could have something to do with it. Then, too, in Laos I was eating white rice every day--virtually with every meal. Sugar was probably around the same as here.

I'm going to try to eat "normal" amounts of meat and fish and eliminate sugar (if I have the will-power!) and see what happens. Any suggestions or ideas would be welcome, or if you have questions so that my experience can help shed light on some of these things I would be happy to answer them.

Thanks!

James said...

Everyone that I know who has experienced gout on a regular irregular basis is using a cup of tart cherries. Works every time. It may not solve your gout problem, but it sure as heck takes the pain away.
By the way, I don't believe the purine story. If it is an inflammation issue, look no further than WGA and lectins in short wheat. Switch to spelt. Did I say say spelt? And don't believe the health nuts who think that you need whole spelt. Spelt flour is a complete nutrient not like wheat where you need the bran and the germ. Get your house in order and ban wheat, anything wheat, anything that has been in the same bag with wheat.

Ibeeza Geeza said...

I cut way down on carbs because I suspected I had candida. I also had gout at the same time. After a few days, I noticed that the gout was really starting to clear up. I had got rid of the gout by accident when trying to sort out the candida!

James said...

I really think we have to look in a different direction. Whatever the case, metabolic syndrome, arthritis, gout,etc. I think at the bottom of it all is inflammation. Arthritis can be relieved by heavy doses of Vitamin C (Pauling)
Both uric acid and ascorbic acid are strong reducing agents (electron donors) and potent antioxidants. In humans, over half the antioxidant capacity of blood plasma comes from uric acid. (European Journal of Clinical Investigation). In other words there must be a reason why the body is producing an overload of uric acid. There must also be a reason why tart cherries (known to fight inflammation)give relief to gout sufferers.
I think purines belong in the category concurrent events. I do not believe there is causality here. James

True Health Services said...

I have observed what I believed to be mycotoxicosis in a few clients who reported they we're suffering from gout. I was viewing the blood of these clients with a high powered microscope at the time. I feel like preliminary research needs to be performed in relation to yeast, fungus and mycotoxins. I am in no position to proclaim that high levels of fungus in someone causes higher Uric acid levels which leads to gout; but I feel this may be the causative mechanism between fructose/sugar and high Uric acid levels. Thank you.

Unknown said...

Potassium deficiency is deeply involved in gout and high uric acid as an accentuating factor because uric acid is less soluble in acidic urine. Potassium bicarbonate supplements will reverse this. In view of the fact that this is not considered by current rheumatologists, it would be very valuable for you to bring it into your future writing. It is not only that potassium is not considered by physicians in regard to gout, many of them do not even believe that a potassium deficiency is likely. This even though many of them prescribe what are actually supplements, but prescribed under euphemistic terms such as salt substitutes, sodium free baking powder, ORT salts (oral rehydration therapy for diarrhea), polarizing solutions, GIK (glucose, insulin, potassium) salts, vegetables, or glucosamine. A deficiency is further defined out of existence by defining the blood serum content normal as 4.2 when the actual figure is 4.8. For gout, though, the chloride is not acceptable. But potassium bicarbonate powder dissolved in fruit juice or half teaspoon sprinkled on cereal will work very well. It may be obtained from businesses which add it to wine. You may see an article on this concept in http://www.webmedcentral.com/article_view/4217 . If you supplement potassium, be very certain that vitamin B-1 is adequate, because otherwise heart disease can be triggered (see http://charles_w.tripod.com/kandthiamin.html ).
Sincerely, Charles Weber

Sarah said...

Getting back to the island study. I have a major Q. Are those on the mainland drinking more fruit juice as compared to whole fruit? Not only is more fructose being ingested, the fibre is less and consuming fruit juices is an "out of season" event. It is easy to drink more than a half or one portion.

Public health authorities place too much emphasis on fruit, fructose consumption. My husband and I have cut way back on fruits, splitting some portions between us to total 3 whole fruit portions per person a week. No juice at all. It helps.