11

votes

Might this Be a Simple Explanation for the Obesity/Diabetes Epidemic (at least in men/post-menopausal women)?

Answered on August 19, 2014
Created July 12, 2011 at 6:15 PM

alt text

We've all probably seen similar graphs and I have for a long time attributed most cases of obesity to prolonged high fructose intakes. What I never stumbled across until now was a proposed mechanism:

http://www.ajcn.org/content/72/5/1128.short

Heavy fructose intake leads to elevated triglycerides.

http://diabetes.diabetesjournals.org/content/53/5/1253.short

Elevated triglycerides lead to reduced transport of leptin across the blood-brain barrier. Without proper leptin signalling, appetite isn't effectively managed, leading to an overall increase in food intake. If fructose constitutes X% of an individual's diet, and fructose increases the volume of food ingested, then it also increases the fructose intake, ensuring that an individual is locked into lipogenesis until fructose is removed.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917125/

RJ Johnson et al have put forth a theory that we have evolved toward an amplification of the effects of fructose by 1) losing the ability to endogenously create ascorbate, which increases the excretion of urate (a by-product of fructose metabolism) and 2) losing the enzyme uricase, which oxidizes uric acid. There was likely a time in our evolutionary history where this fructose-induced increase in adiposity was welcome and probably ensured our survival. Clearly, this is no longer the case.

Interestingly, the consumption of yeast also spikes uric acid due to the large amount of RNA that is being consumed (the breakdown of nucleotides leads to uric acid production). Perhaps a diet consisting of heavy bread/beer/fructose intake is even worse than fructose alone. Theobromine, present in chocolate and a byproduct of caffeine metabolism has the highest concentration of purines that I've seen. All of these things seem to factor heavily into the diets of the people residing in countries with the highest obesity rates.

https://www.ncbi.nlm.nih.gov/pubmed/16234313

This study showed that insulin resistance, hypertension, high triglycerides and weight gain were prevented by giving fructose-fed rats a uric-acid reducing agent as well. It seems to me that uric acid management is the key to all of this and that a simple approach to reverse/prevent obesity would simply be:

Avoid: fructose, bread and beer
Increase: vitamin c from low fructose sources (red bell peppers, strawberries etc.)

Edit: It occurs to me that the actual number of grams of theobromine ingested would probably be insignificant and that theobromine toxicity would likely be encountered before you ever got enough purines from it.

1a98a40ba8ffdc5aa28d1324d01c6c9f

(20378)

on August 15, 2011
at 03:09 AM

Very Nice Question!!!!

Medium avatar

(39831)

on July 13, 2011
at 05:36 PM

http://jcem.endojournals.org/content/89/6/2963.abstract Seems to at least temporarily affect women actually

E7a462d6e99fec7e8f0ddda11b34a770

(1638)

on July 13, 2011
at 01:56 PM

Thanks - evidently I got 2 anonymous down votes for this answer too, so I doubly appreciate it.

Medium avatar

(10611)

on July 13, 2011
at 03:50 AM

Interesting demonstraton of evolutionary adaptation over only 10 generations. As a linear process there's no going back. You have to make better eating choices deliberately since you've been adapted to gorge on fructose.

667f6c030b0245d71d8ef50c72b097dc

(15976)

on July 13, 2011
at 01:38 AM

Very nteresting. Thanks for posting that. We tend to be preaching to the choir sometimes.

Medium avatar

(39831)

on July 13, 2011
at 12:27 AM

Here's the obesity one: http://www.ajcn.org/content/86/4/899.full

Medium avatar

(39831)

on July 13, 2011
at 12:20 AM

The diabetes prevalence maps similarly: http://edrv.endojournals.org/content/30/1/96.full

21fd060d0796fdb8a4a990441e08eae7

(24543)

on July 13, 2011
at 12:18 AM

Where do you learn those emoticons from? The complex ones never translate well for me. This koala, for example, doesn't really work C(*o*)O

Medium avatar

(39831)

on July 13, 2011
at 12:18 AM

I mean specifically with regard to fructose. I don't know what the mechanism is.

21fd060d0796fdb8a4a990441e08eae7

(24543)

on July 13, 2011
at 12:15 AM

What did I say about using emoticons, Melissa?? By the way, look at this koala @(*o*)@

21fd060d0796fdb8a4a990441e08eae7

(24543)

on July 13, 2011
at 12:15 AM

What did I say about those emoticons Melissa? By the way, look at this koala C(*@*)O

3a2f98fb863f39ce37c560942bbf6ead

(18)

on July 12, 2011
at 11:57 PM

Also, theobromine is a vasodilator so it lowers blood pressure and there's some pretty good evidence in the last few years that it has "anti-coughing" effects too. Better to go for dark choc or straight cocoa powder though, don't want to rot your teeth :)

66e6b190e62fb3bcf42d4c60801c7bf6

(12407)

on July 12, 2011
at 11:52 PM

here 'tis... i believe i'm reading it correctly. http://www.ncbi.nlm.nih.gov/pubmed/18703413

Fa9f340eddbad9a544184c688fa4dcdd

(6433)

on July 12, 2011
at 10:28 PM

Thanks for that - you've reassured me. :)

8949bf87b0e0aefcad10f29975e4fa2b

(8989)

on July 12, 2011
at 10:01 PM

Oh, I get it. But, how is estrogen protective? While I believe that it is true that women do tend to gain more weight after menopause, look at all the fat younger women, especially after having kids. Estrogen doesn't seem to be protecting anything there.

66e6b190e62fb3bcf42d4c60801c7bf6

(12407)

on July 12, 2011
at 09:39 PM

and it doesn't correlate with gout. from my n=3(me, my father and bro all have gout)fructose is the primary driver of gout. we all eat plenty of the purine rich foods they made us stay away from for years with no ill effect...

Medium avatar

(39831)

on July 12, 2011
at 09:30 PM

I think it's estrogen itself that has a protective effect.

66e6b190e62fb3bcf42d4c60801c7bf6

(12407)

on July 12, 2011
at 09:20 PM

Sugar is big and so are the oils and gluten. All of them seem to work in concert to cause systemic inflammation. It wasn't until I threw out all 3 together I was able to reverse the metabolic derangement. I've seen a rat study where rats tended to overeat on fat(didn't specify what kind) AFTER being fed a high fructose diet over an extended period of time. I have to find that study.

Medium avatar

(39831)

on July 12, 2011
at 09:00 PM

Fructose raises fasting triglycerides in addition to post-prandial TGs.

E35e3d76547b18096a59c90029e7e107

(15613)

on July 12, 2011
at 08:39 PM

I wouldn't worry about 85% chocolate. 15g sugar/7.5g carbs per 100g bar isn't much and I can't even eat a whole bar, despite my prodigious fat eating abilities and love of 100% cocoa (too much caffeine/tannins) and re. the purines meat and offal also contain purines, which given the higher proportion of meat in one's diet compared to chocolate, I'm sure means that high purine intake doesn't correlate with obesity.

9a5e2da94ad63ea3186dfa494e16a8d1

(15833)

on July 12, 2011
at 08:35 PM

I have never seen that (not saying it doesn't happen, just in my experience haven't seen it), whereas there are a lot of testimonials (here and elsewhere) that quitting gluten had major effects. I would be curious to get some kind of broad numbers on this.

Medium avatar

(39831)

on July 12, 2011
at 08:24 PM

I've read several accounts by people claiming that simply cutting out sugar was enough to bring about significant losses in fat mass. Couldn't tell you if they were true though. I think factors that cause fat gain don't necessarily lead to a commensurate fat loss when removed.

7e746be2f0e550a8cd7df881322ae705

(18701)

on July 12, 2011
at 08:19 PM

85% Dark Lindt. /o/\o\

E35e3d76547b18096a59c90029e7e107

(15613)

on July 12, 2011
at 08:19 PM

I wouldn't worry about 85% chocolate. 15g sugar/7.5g carbs per 100g bar isn't much and I can't even eat a whole bar, despite my prodigious fat eating abilities and love of 100% cocoa (too much caffeine/tannins).

Medium avatar

(39831)

on July 12, 2011
at 07:07 PM

Maybe one bell pepper per chocolate bar should even things out? I doubt that chocolate itself is going to make a huge difference, but it can't help on top of everything else.

Medium avatar

(39831)

on July 12, 2011
at 06:57 PM

I'd also say that if NHANES or whatever spits out a number like 73g of fructose a day on average, then it might just be that because junk food has changed and because there are far more enticing opportunities to eat huge amount of fructose now, the really heavy fructose intake outlier people are eating quite a lot more. They then would be the fattest among us and wouldn't necessarily honestly/accurately report their sugar intake.

Be1dbd31e4a3fccd4394494aa5db256d

(17969)

on July 12, 2011
at 06:52 PM

Ah yeah, that whole debate. I don't know what to make of it, I'm just avoiding all of that stuff.

21fd060d0796fdb8a4a990441e08eae7

(24543)

on July 12, 2011
at 06:50 PM

Good point. Unfortunately, not a lot of randomized trials around on obesity prevention. Trial participants tend to be f'd metabolically, so it's hard to extrapolate. Where's the money NIH??!

Medium avatar

(39831)

on July 12, 2011
at 06:47 PM

If HFCS has increased from 16% of sweeteners in 1978 to 42% in 2004, then the amount of free fructose molecules (not bound to glucose, as with sucrose) would have increased significantly. I don't know if metabolism is the same.

Fa9f340eddbad9a544184c688fa4dcdd

(6433)

on July 12, 2011
at 06:40 PM

Reluctantly upvoted as a smart question by a lover of Lindt's 85% chocolate. :)

Medium avatar

(39831)

on July 12, 2011
at 06:40 PM

Additionally, I think this is more effective for prevention compared to reversal. Once obese, it's likely going to take quite a bit more.

Medium avatar

(39831)

on July 12, 2011
at 06:39 PM

Perhaps the "natural fruit supplement" had a fair amount of vitamin C.

50637dfd7dc7a7e811d82283f4f5fd10

(5838)

on July 12, 2011
at 06:37 PM

Great question, Travis. +1

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9 Answers

4
Be1dbd31e4a3fccd4394494aa5db256d

(17969)

on July 12, 2011
at 06:38 PM

I think that you have demonstrated sugar to be a player with the triglycerides, but there is no simple answer. There are many factors that go into metabolic syndrome and leptin resistance and they all make each other worse. We have here a plausible mechanism, but in the case of humans living their lives it is harder to say if it is all the sugar. We have a plausible mechanism but the important thing to note about metabolic syndrome is that there is no single cause, only many things that come together to aggravate it.

This is a great chart of dietary trends since the 70s. http://civileats.com/2011/04/05/where-do-americans-get-their-calories-infographic/

Sugar hasn't really gone up much, grains have gone up and "added fat" (seed oils) have skyrocketed. I think that sugar was probably a big contributor to obesity in the 70s, and it is a factor in itself when people get a whopping 450 calories from it in a day, but the seed oils and wheaty grain "products" also have plausible mechanisms to suggest that they are big players.

Medium avatar

(39831)

on July 12, 2011
at 06:47 PM

If HFCS has increased from 16% of sweeteners in 1978 to 42% in 2004, then the amount of free fructose molecules (not bound to glucose, as with sucrose) would have increased significantly. I don't know if metabolism is the same.

Medium avatar

(39831)

on July 12, 2011
at 06:57 PM

I'd also say that if NHANES or whatever spits out a number like 73g of fructose a day on average, then it might just be that because junk food has changed and because there are far more enticing opportunities to eat huge amount of fructose now, the really heavy fructose intake outlier people are eating quite a lot more. They then would be the fattest among us and wouldn't necessarily honestly/accurately report their sugar intake.

Be1dbd31e4a3fccd4394494aa5db256d

(17969)

on July 12, 2011
at 06:52 PM

Ah yeah, that whole debate. I don't know what to make of it, I'm just avoiding all of that stuff.

3
66e6b190e62fb3bcf42d4c60801c7bf6

on July 12, 2011
at 06:33 PM

you'll have to pry my lindt from my cold dead hands!!!

but seriously, that's good stuff. i've been reading up on excessive fructose and it's effects on triglycerides also and this sounds very plausible.

7e746be2f0e550a8cd7df881322ae705

(18701)

on July 12, 2011
at 08:19 PM

85% Dark Lindt. /o/\o\

21fd060d0796fdb8a4a990441e08eae7

(24543)

on July 13, 2011
at 12:15 AM

What did I say about using emoticons, Melissa?? By the way, look at this koala @(*o*)@

21fd060d0796fdb8a4a990441e08eae7

(24543)

on July 13, 2011
at 12:18 AM

Where do you learn those emoticons from? The complex ones never translate well for me. This koala, for example, doesn't really work C(*o*)O

21fd060d0796fdb8a4a990441e08eae7

(24543)

on July 13, 2011
at 12:15 AM

What did I say about those emoticons Melissa? By the way, look at this koala C(*@*)O

2
E35e3d76547b18096a59c90029e7e107

(15613)

on July 12, 2011
at 08:42 PM

Unfortunately you can show that same association for a host of other variables too: calorie consumption, economic inequality, PUFA consumption, wheat consumption, processed food consumption and so on... (I even saw one linking niacin to the post-70s obesity epidemic). No wonder people just wave their hand at the whole of "the industrial lifestyle."

As to the fructose disturbing leptin point. Yes, this is important to remember, but I don't think it's a plausible candidate for the obesity epidemic. The disruption of leptin (and also ghrelin if I recall correctly, I've talked about both on here before) is temporary, so you would expect mere hours after a fructose meal leptin sensitivity would return. Although I can see why fructose could cause weight gain to a moderate extent, one would think that obese people, after a suitable period without fructose would have a crushing lack of appetite. This also doesn't seem to make sense of people eating large quantities of starch and fat, which seems common.


Edit:

So Travis makes a good point, which I'd completely missed, namely that fructose increases fasting as well as post-prandial triglycerides. Presumably this is why he suggests only in men and post-menopausal women, because the paper only shows a difference from fructose vs glucose feeding in men. On its own, this makes me suspicious that this is a dominant mechanism- it would be odd if men and women have both gotten obese, but through independent mechanisms.

Having looked at table 3, I find it a bit mysterious that both groups have declining triacylglycerols throughout. Also interesting is that the glucose men, after 7 days, have fasting levels significantly below baseline for their group.

The men started at 1.325mmol/L- after a week the fructose group were minimally higher at 1.34 (the highest they got and had lower levels than baseline every week thereafter), whereas the glucose group after a week are on 1.11mmol/L significantly below baseline levels, and they decrease pretty steadily throughout the study.

might-this-be-a-simple-explanation-for-the-obesity/diabetes-epidemic-(at-least-in-men/post-menopausal-women)?

A quick and neat explanation for why this is the case might be that the men were consuming lots of fructose prior to the study, at baseline and so the fructose group more or less remained where they were (or, in fact, consumed a little less fructose and improved) whereas the enforced glucose/low fructose group steadily improved. But this seems somewhat unlikely since the fructose group were eating 17% of calories from fructose, whereas the study cites average intake as 9% (in 1988, it's increased a bit since then, but not that much, since fructose intake has only increased 19% since 1970.

Medium avatar

(39831)

on July 13, 2011
at 05:36 PM

http://jcem.endojournals.org/content/89/6/2963.abstract Seems to at least temporarily affect women actually

Medium avatar

(39831)

on July 12, 2011
at 09:00 PM

Fructose raises fasting triglycerides in addition to post-prandial TGs.

1
E7a462d6e99fec7e8f0ddda11b34a770

(1638)

on July 12, 2011
at 08:33 PM

I have been a sugar junkie since I was a little kid and it is still my biggest issue in transitioning my diet to a paleo/primal one and attempting to lose the 40-50 extra lbs that I am carrying. BUT, my trigs have consistently been under 70 for the last 10yrs or so at least and are currently sitting at 45.

So, either I am an outlier or there are other factors involved like some have suggested.

E7a462d6e99fec7e8f0ddda11b34a770

(1638)

on July 13, 2011
at 01:56 PM

Thanks - evidently I got 2 anonymous down votes for this answer too, so I doubly appreciate it.

667f6c030b0245d71d8ef50c72b097dc

(15976)

on July 13, 2011
at 01:38 AM

Very nteresting. Thanks for posting that. We tend to be preaching to the choir sometimes.

1
21fd060d0796fdb8a4a990441e08eae7

(24543)

on July 12, 2011
at 06:34 PM

I would suspect that uric acid reduction would not have the same effect in humans.

If gout medication led to weight loss, one would think that that effect would have been noticed, and even recorded in gout clinical trials. Actually, one possible side effect of the uric acid reducer allopurinol is weight gain. So things may be more complex.

One explanation for this might be that eating in humans differs from lab feeding in rats in two major ways: we are humans with different physiology, and we are free to eat what we want.

In addition, some randomized trials have shown greater weight loss with fructose-containing diets compared to low-fructose diets:

http://www.bodyrecomposition.com/research-review/the-effect-of-two-energy-restricted-diets-a-low-fructose-diet-vs-a-moderate-natural-fructose-diet-research-review.html

21fd060d0796fdb8a4a990441e08eae7

(24543)

on July 12, 2011
at 06:50 PM

Good point. Unfortunately, not a lot of randomized trials around on obesity prevention. Trial participants tend to be f'd metabolically, so it's hard to extrapolate. Where's the money NIH??!

Medium avatar

(39831)

on July 12, 2011
at 06:40 PM

Additionally, I think this is more effective for prevention compared to reversal. Once obese, it's likely going to take quite a bit more.

Medium avatar

(39831)

on July 12, 2011
at 06:39 PM

Perhaps the "natural fruit supplement" had a fair amount of vitamin C.

0
3a2f98fb863f39ce37c560942bbf6ead

on July 13, 2011
at 12:00 AM

Sorry, I don't actually have an answer for you but could you supply the reference for the graph you posted please, I can't seem to find it (sorry if I'm being stupid)

Medium avatar

(39831)

on July 13, 2011
at 12:27 AM

Here's the obesity one: http://www.ajcn.org/content/86/4/899.full

Medium avatar

(39831)

on July 13, 2011
at 12:20 AM

The diabetes prevalence maps similarly: http://edrv.endojournals.org/content/30/1/96.full

0
8949bf87b0e0aefcad10f29975e4fa2b

(8989)

on July 12, 2011
at 09:13 PM

The graph is a nightmare, cobbling together relatively unrelated data from several sources, and it is trying to get the untrained eye to be convinced of some sort of correlation. It should be ignored. In addition, the information is based on studies of men, and I fail to see how that would automatically apply to post-menopausal women. That said, there might still be something to your theory, or at least account for some of the increases in obesity. I know it is has not much to do in my case, as I ate an exemplary vegetarian whole-grain diet for many years before I became obese.

Medium avatar

(39831)

on July 12, 2011
at 09:30 PM

I think it's estrogen itself that has a protective effect.

8949bf87b0e0aefcad10f29975e4fa2b

(8989)

on July 12, 2011
at 10:01 PM

Oh, I get it. But, how is estrogen protective? While I believe that it is true that women do tend to gain more weight after menopause, look at all the fat younger women, especially after having kids. Estrogen doesn't seem to be protecting anything there.

Medium avatar

(39831)

on July 13, 2011
at 12:18 AM

I mean specifically with regard to fructose. I don't know what the mechanism is.

0
51c2cdd55bf287026db68cf31a6d0a0b

on July 12, 2011
at 08:06 PM

This is very interesting to me for two reasons.

1, I have had a bit of an issue with dried fruits lately. I love them but then figured that was because it gave me my sugar fix and I could kid myself that 'cos they were fruit they were healthy. Of course I know this isn't the case and while dried fruits in moderation are OK, (I hope) the fructose in them is something that we should try and stay away from. While I've been told this by quite a few people, seeing it in this way really does prove what I have had niggling at the back of my brain for a few weeks.

2, I can use it to shut up all the people at work who think I'm a weirdo for not eating one of the doughnuts they brought in. :)

Thanks for posting it!

Paul.

0
9a5e2da94ad63ea3186dfa494e16a8d1

on July 12, 2011
at 07:58 PM

I don't think it is any one thing or any 3 ingredients all by themselves. If it were just sugar for example that was causing widespread obesity and disease, then simply cutting out sugar would cause widespread weight loss and health improvements, which it doesn't. Cutting out sugar is a good thing in general, but all by itself won't make you lose 50 pounds.

My personal opinion is that beer itself isn't a major contributor to obesity, but many of the things that go along with it are (sitting on the couch and watching tv, eating chips and wings, etc), i.e. the "beer lifestyle" contributes towards these problems, but beer itself is pretty low on the offender list. Sugary drinks for example I think are much worse.

I think bread and related "processed grain products" are a major factor for the subset of the population that is sensitive to gluten, which I think is a bigger subset than many people think.

The bad oils and fats also I think are a problem, but all by themselves don't really explain everything.

More than any of these things, I think it is the broad trend towards food that is highly processed and lacking in nutrition that is "the problem". These foods are high in all of these things, and also cause people to avoid eating "real" food.

The best all-encompassing explanation I've heard is the "insulin response" theory, which I think is likely correct or close enough to being correct. Also the theory that most problems are the result of inflammation, and thus indirectly by things that cause inflammation. You could probably come up with some trend charts over the past 50-70 years that show massive increases in foods and activities that exacerbate this basic problem.

9a5e2da94ad63ea3186dfa494e16a8d1

(15833)

on July 12, 2011
at 08:35 PM

I have never seen that (not saying it doesn't happen, just in my experience haven't seen it), whereas there are a lot of testimonials (here and elsewhere) that quitting gluten had major effects. I would be curious to get some kind of broad numbers on this.

66e6b190e62fb3bcf42d4c60801c7bf6

(12407)

on July 12, 2011
at 09:20 PM

Sugar is big and so are the oils and gluten. All of them seem to work in concert to cause systemic inflammation. It wasn't until I threw out all 3 together I was able to reverse the metabolic derangement. I've seen a rat study where rats tended to overeat on fat(didn't specify what kind) AFTER being fed a high fructose diet over an extended period of time. I have to find that study.

66e6b190e62fb3bcf42d4c60801c7bf6

(12407)

on July 12, 2011
at 11:52 PM

here 'tis... i believe i'm reading it correctly. http://www.ncbi.nlm.nih.gov/pubmed/18703413

Medium avatar

(39831)

on July 12, 2011
at 08:24 PM

I've read several accounts by people claiming that simply cutting out sugar was enough to bring about significant losses in fat mass. Couldn't tell you if they were true though. I think factors that cause fat gain don't necessarily lead to a commensurate fat loss when removed.

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