How to interpret research part I - Fructose

MrRippedZilla

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I did want to use this sub-forum to help people separate the good from the bad science and the easiest way to do this is to focus on the bad while explaining exactly WHY it is so bad. So here we are...


Consuming fructose, not glucose, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humanshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673878/


Abstract
Studies in animals have documented that, compared with glucose, dietary fructose induces dyslipidemia and insulin resistance. To assess the relative effects of these dietary sugars during sustained consumption in humans, overweight and obese subjects consumed glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks.
Although both groups exhibited similar weight gain during the intervention, visceral adipose volume was significantly increased only in subjects consuming fructose.
Fasting plasma triglyceride concentrations increased by approximately 10% during 10 weeks of glucose consumption but not after fructose consumption. In contrast, hepatic de novo lipogenesis (DNL) and the 23-hour postprandial triglyceride AUC were increased specifically during fructose consumption. Similarly, markers of altered lipid metabolism and lipoprotein remodeling, including fasting apoB, LDL, small dense LDL, oxidized LDL, and postprandial concentrations of remnant-like particle-triglyceride and -cholesterol significantly increased during fructose but not glucose consumption.
In addition, fasting plasma glucose and insulin levels increased and insulin sensitivity decreased in subjects consuming fructose but not in those consuming glucose.
These data suggest that dietary fructose specifically increases DNL, promotes dyslipidemia, decreases insulin sensitivity, and increases visceral adiposity in overweight/obese adults.

I want to make it very clear that I absolutely hate this paper, for reasons that will become apparent as you read on, and so if your interested in a more "friendly" form of critique then I recommend checking this out instead.


Methodology

This study is a classic example of some researchers being so far up their own asses that getting published is more important than producing results that have even a slight whiff of reality to them. The study design is so flawed that, no matter how accurate the results are, it simply doesn't matter in real life because this specific scenario NEVER happens in real life.

Let's start with some baseline stats of the subjects:
- Sedentary men & women in their 50s.
- Both sexes are extremely obese with men around the high 20's & women low 40's for bf%.
- No significant differences to start with when it comes to lipids, glucose, insulin or other parameters between the two groups.
- Full stats can be seen here.
So they took these sedentary, and very fat, subjects and put them into either a "fructose" or "glucose" group consuming a diet composed of 55% carbs (25% from fructose/glucose), 30% fat, 15% protein.
The study involved a 2 week control period to establish baseline stats, then 8 weeks ad-libitum (eat whatever you want, no tracking, as long as it includes the 25% fructose/glucose), and 2 weeks control to finish for final assessments.

Now let's get the positives out of the way before I rant.
During the initial and end 2 week phases, diet was completely controlled by the lab and they did use a bunch of cool assessment tools.
The initial phase established dietary maintenance along with a wide range of clinical indexes being assessed like DEXA for body comp, CT scans for visceral & sub fat, needle biopsy's of adipose tissue to assess gene expression and measuring DNL.
Unfortunately, no matter how thorough your methods of assessment, it will all be a giant waste of funds if what your actually assessing is pointless & retarded...

Immediately, we have an ethical issue here.
Considering one of the main reasons a lot of pharmaceutical research never gets done is due to the fear of harming the subjects involved, why the **** were extremely obese, sedentary, people allowed to consume a fantasy amount of sugar? I have no answer.
The researches knew damn well that these folks would overeat during the ad libitum phase and therefore get fatter, increase insulin resistance & lipid levels - they just wanted to know which sugar would do the most damage. This study already smells bad.

Then we have this issue - WHY WOULD YOU MAKE ALMOST LITTLE ATTEMPT TO CONTROL THE VARIABLES DURING THE 8 WEEK AD-LIBITUM MIDDLE PHASE?
As a result of this complete lack of dietary control both groups gained weight & fat during the ad-libitum phase only. This goes back to the researchers knowing exactly what was going to happen - they wanted these subjects to become more unhealthy.

And the biggest issue of them all, and the reason why the study design makes this study WORTHLESS, the dosing of fructose and glucose used here would be close to IMPOSSIBLE to find in real life.
Specifically, there is NO soft-drink that is sweetened exclusively with fructose or glucose only. Most, if not ALL, non-diet soft drinks are sweetened with sucrose, high fructose corn syrup, etc - these ingredients contain a mix of fructose/glucose that tends to be around 50/50.

To illustrate how RETARDED this dosing was, let's break it down even further.
They had 25% of total cals coming from these drinks = approx 600 cals = 150g of either fructose or glucose.
To achieve that total in real life you would need to drink around 7 CANS OF NONDIET SODA EVERYDAY - who the **** does this?

The authors then have the balls admit, and reference, the fact that the average sugar intake of Americans is around 15.8%. Since fructose makes up half of that, we're talking about 7.9% of the daily diet - not even CLOSE to the 25% used in this study.
AFAIC, this is the authors pretty much admitting that this was going to be a bunch of mental masturbation with ZERO influence on reality. I did mention that I hate this paper right?


Results & discussion

Considering the fantasy-booked nature of the diet, I honestly couldn't give a shit about the results of this paper but for those interested we have changes in bodyweight & fat, glucose & insulin response along with lipid & DNL levels that give the general, misleading, picture that fructose is worse than glucose.

I can hear you readers saying "surely the researchers aren't that impractical, they must have found some evidence to support the 25% dosing?"
Unfortunately, impracticality is what a lot of researchers specialize in. Even if the 25% figure is supported in SOME populations, like college students we still have the issue of sugar being half fructose & half glucose. So even in that scenario fructose intake would only make up 12.5%, NOT 25%, of the diet.

To really drive home the retarded nature of the study design used, here are a few examples of what getting 25% of your diet from fructose would actually look like for someone who maintains at around 2000-4000cals:
- 42-84 tsp of sugar.
- 20-40 apples (one of the higher fructose fruits)
- 300-600g of honey
- 7-14 cans of nondiet soda

Assuming we all agree on the impracticality of this paper, I'm left with 2 explanations for the methodology used:
- As I've stated before, this was simply an exercise in mental masturbation or as another researcher so eloquently put it:
" "Thus, studies using extreme carbohydrate diets may be useful for probing biochemical pathways, but they have no relevance to the human diet or to current consumption.""

- The researchers were simply doing what it takes to get published with no interest in having their data translated to helping people in real life.
The chances of getting published dramatically fall when you find no difference between groups in your study or results that have already been published and either scenario was high likely in a more realistic study design. You need something new and exciting that preferably creates significant differences...hence the study design here.
Disgraceful, mental jacking off, bullshit that benefits no one but the authors themselves AFAIC.


Take home points

If your a fat, inactive, person on a hypercaloric diet do NOT drink multiple cans of nondiet soda drinks every day - it can lead to dyslipidemia, insulin resistance, increased DNL, TG levels, etc.
This practice can become even more harmful if your a wizard with access to a special lab to get your hands on some fructose-only soda drinks.
While we're at it, you might want to address the "fat", "inactive" and/or "hypercaloric" parts of the equation too. Just saying.

Sarcasm aside, the real take home point here is to LEARN HOW TO INTERPRET DATA so that you can rule out the bad from the good science.
Don't be one of the many fitness media monkeys who will misapply study conclusions without paying any attention to the fantasy methodology used. This leads to consumers reading these headlines and mistakenly equating massive consumption of isolated fructose to eating a few pieces of fruit per day and on & on the cycle goes.

When you only read the abstract/conclusion to the paper like this and then read the methodology behind it, man, does the picture change dramatically :)
 
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PillarofBalance

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"Don't be one of the many fitness media monkeys who will misapply study conclusions "

*cough* Gary taubes *cough*
 

automatondan

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One of the thoughts that also comes to mind when I am/was researching, is that every paper has a bias. No matter what is observed. There is always a bias. I think that is something we should always consider when reading a paper.

Case in point, this paper. The "researchers" basically set up unrealistic circumstances that they knew would elicit the specific results they were after.
 
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MrRippedZilla

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One of the thoughts that also comes to mind when I am/was researching, is that every paper has a bias. No matter what is observed. There is always a bias. I think that is something we should always consider when reading a paper.

Case in point, this paper. The "researchers" basically set up unrealistic circumstances that they knew would elicit the specific results they were after.

Good science doesn't have a bias but I do agree that it is a major issue in the vast majority of the research. Not to mention it being one of the reasons why folks dismiss the value science in the first place, you read a bad study and assume its all nonsense and leave it at that.

You do raise a very good point since this form of bias, the sacrifice of good study design & methodology in order to gain a particular overall outcome, isn't what most people think of when they think of "bias". They usually think of "bias" as being against the truth or favoring 1 particular group in a study (due to commercial interests, etc) which wasn't the case here.

There was actually another paper published by the International Life Sciences Institute (ILSI) around the same time that goes into much greater depth on this topic. Unfortunately, since those guidelines were published in 2009, bias is still very much alive & well in the published data.
Money shouts a lot louder than the truth it seems but nevertheless the guidelines in that paper are worth quoting -


"All relevant parties shall:

1) Conduct or sponsor research that is factual, transparent, and designed objectively, and, according to accepted principles of scientific inquiry, the research design will generate an appropriately phrased hypothesis and the research will answer the appropriate questions, rather than favor a particular outcome;

2) Require control of both study design and research itself to remain with scientific investigators;

3) Not offer or accept remuneration geared to the outcome of a research project;

4) Ensure, before the commencement of studies, that there is a written agreement that the investigative team has the freedom and obligation to attempt to publish the findings within some specified time frame;

5) Require, in publications and conference presentations, full signed disclosure of all financial interests;

6) Not participate in undisclosed paid authorship arrangements in industry-sponsored publications or presentations;

7) Guarantee accessibility to all data and control of statistical analysis by investigators and appropriate auditors/reviewers;

8) Require that academic researchers, when they work in contract research organizations (CRO) or act as contract researchers, make clear statements of their affiliation; and require that such researchers publish only under the auspices of the CRO."


Guideline no.1 was the issue here, no.3 is never likely to happen.
 
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MrRippedZilla

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Continuing our fructose related theme...


Fructose overconsumption causes dyslipidemia and ectopic lipid deposition in healthy subjects with and without a family history of type 2 diabetes


Abstract
Background:
Both nutritional and genetic factors are involved in the pathogenesis of nonalcoholic fatty liver disease and insulin resistance.

Objective:
The aim was to assess the effects of fructose, a potent stimulator of hepatic de novo lipogenesis, on intrahepatocellular lipids (IHCLs) and insulin sensitivity in healthy offspring of patients with type 2 diabetes (OffT2D)—a subgroup of individuals prone to metabolic disorders.

Design:
Sixteen male OffT2D and 8 control subjects were studied in a crossover design after either a 7-d isocaloric diet or a hypercaloric high-fructose diet (3.5 g · kg FFM−1 · d−1, +35% energy intake). Hepatic and whole-body insulin sensitivity were assessed with a 2-step hyperinsulinemic euglycemic clamp (0.3 and 1.0 mU · kg−1 · min−1), together with 6,6-[2H2]glucose. IHCLs and intramyocellular lipids (IMCLs) were measured by 1H-magnetic resonance spectroscopy.

Results:
The OffT2D group had significantly (P < 0.05) higher IHCLs (+94%), total triacylglycerols (+35%), and lower whole-body insulin sensitivity (−27%) than did the control group. The high-fructose diet significantly increased IHCLs (control: +76%; OffT2D: +79%), IMCLs (control: +47%; OffT2D: +24%), VLDL-triacylglycerols (control: +51%; OffT2D: +110%), and fasting hepatic glucose output (control: +4%; OffT2D: +5%). Furthermore, the effects of fructose on VLDL-triacylglycerols were higher in the OffT2D group (group × diet interaction: P < 0.05).

Conclusions:
A 7-d high-fructose diet increased ectopic lipid deposition in liver and muscle and fasting VLDL-triacylglycerols and decreased hepatic insulin sensitivity. Fructose-induced alterations in VLDL-triacylglycerols appeared to be of greater magnitude in the OffT2D group, which suggests that these individuals may be more prone to developing dyslipidemia when challenged by high fructose intakes.


Methodology

Unlike the last fructose paper we looked at, which was utter mental masturbation, this one actually does at least look at an important area - the role of genetics in the risk of developing disease. All the subjects were healthy and of normal weight, which bypasses the ethical issues in the previous one, and the key difference was that 1 group was made up exclusively of people who's parents had type 2 diabetes (T2D).

Diet composition was 55% carbs, 30% fats, 15% protein - an accurate reflection of the average western diet but probably not of anyone who's actually reading this.
Physical activity was limited to 1hr/week so obviously the implications here are probably limited to the sedentary population.

The big limitation, and what makes both the title & abstract conclusion of this paper bullshit, was that the fructose dose was added ON TOP of the existing diet rather than simply replacing a portion of the current carb intake.
Therefore, it becomes impossible to determine whether the resulting effects were due to the fructose consumption or caloric surplus per se - so saying that "fructose overconsumption causes" anything, as the title & abstract do, is bullshit. It would be more accurate to say that fructose and/or caloric overconsumption causes a,b,c,d.
This is the key point to the whole context of this paper and only becomes obvious if you know how to interpret research properly rather than relying on the title and abstract conclusions.


Results & discussion

The key results can be found here and here with the main points being:

1) Leptin went up dramatically (1.3ng/ml) only in the T2D group, which is interesting for a lot of reasons I won't go into here.

2) The high fructose diet increased VLDL-TG, intrahepatocellular (ICHL) and intromyocellular (IMCL) lipids. The MOA behind this is likely the increased hepatic DNL = inhibited tissue lipid oxidation.

3) Subjects with T2D parents, who are healthy & normal themselves, do suffer with higher ICHL & VLDL-TG levels. This has important health implications because T2D themselves do have a higher risk of developing non-alcholic fatty live disease, which is characterized by ICHL accumulation and fructose-driven increases in fatty acid synthesis within the liver.

Now, let's put these results in perspective.
The dose used, again, was on the retarded side in order to force the occurrence of adverse metabolic outcomes - this type of bias was discussed in part I and was very much at play again here. The fructose dose was 3.5g/kg FFM, which averages 215g ON TOP of the regular diet for the 7 day experiment.
As a result, we have a 35% caloric surplus. To achieve this fructose dose in real life, you would need to drink around 10-11 nondiet soda cans per day and don't get me started on fruit (you should NOT be avoiding fruit because of the ****ing fructose content).
As a result of these practical limitations, the fructose warnings from this and the previous study I dissected need to be ignored as far as reality is concerned.


Take home points

- If your bulking, then don't do anything stupid when it comes to fructose intake; especially if your a higher risk individual who comes from a family of T2Ds.
- Do NOT assume that a study title & abstract tells you everything you need to know about the main points of the paper. Always try to find out the methodology behind the research and interpret said research in the right context.
 
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