Does sugar truly cause heart disease? Evidence and explanations behind the link

[lavinia]

Recently I viewed a short video that recommended reducing sugar in our diets because new research suggests that sugar causes heart disease. What is the status of this research? How convincing is the evidence?

 

[Greg Bernhardt]

Here is a study from back in April

Added Sugar Intake and Cardiovascular Diseases Mortality Among US Adults
http://archinte.jamanetwork.com/article.aspx?articleid=1819573

btw, can you post the video?

@Ygggdrasil

 

[lavinia]

Here is a study from back in April

Added Sugar Intake and Cardiovascular Diseases Mortality Among US Adults
http://archinte.jamanetwork.com/article.aspx?articleid=1819573

btw, can you post the video?

The video appears on the Kripalu yoga institute website. It is not a scientific discourse but more a discussion of how to reduce sugar intake. I also found some papers on line that indicated that sugar is toxic to the heart and was wondering how accepted this evidence is.

 

[jim mcnamara]

Here is a suitable discussion at the NIH website discussing CVD and sugar intake:
http://www.ncbi.nlm.nih.gov/pubmedhealth/behindtheheadlines/news/2014-02-04-sugar-intake-linked-to-heart-disease-deaths/

It cites a JAMA paper that finds 2.75 times increased CVD in persons consuming 25% or more of their calories as sugar. (NIH recommends a 10% maximum. With a tacit suggestion to avoid sugar as much as possible in parallel sources)

I would go with this point of view, rather than the Kripalu Yoga Institute's version of things. Bottom line: lots of calories from simple sugars in your diet is bad long term.

 

[gravenewworld]

Sugar is directly linked to reprogramming the entire way your cell functions (cancer, diabetes, AZ are all characterized by abnormal glucose metabolism/consumption). I know I sound like a crazy person for constantly talking about the O-glcnac modification on these forums, but it is absolutely a thing of beauty--and I wouldn't be surprised that years from now it would be Nobel worthy.

First, some background. Protein physiology is almost always shown in cascade cartoons as being like on/off switches via phosphorylation, however it is becoming increasingly clear that this is a grossly oversimplified model. The O-glcnac modification (which is the addition the sugar N-acetylglucosamine) occurs on proteins at Ser/Thr residues in proteins and many times these Ser/Thr residues are the same exact sites where protein phosporylation occurs. If you can start to see the bigger picture, the significance of O-glcnacylation can not be understated. It behaves as a 'cap' almost to block sites from being phosphorylated on proteins. In otherwords, our models of protein physiology are vastly oversimplified because you are ignoring the fact that proteins should have multiple sites for not only phosphorylation but also for O-glcnacylation (plus mutiple combinations thereof between the two) and need to include some sort of extremely complex cycling mechanism between both phosphorylation addition/removal and addition/removal of O-GlcNAc.

Consider how many hundreds, if not thousands, or kinases and phosphatases that exist in order to regulate the phosphorylation status of the proteome. Contrast that to the O-glcnac modifcation which is controlled by only 2 enzymes--OGT which adds it to proteins and OGA which removes it, that's it (why it's mechanism and discovery is so beautiful). We now know that almost every cytosolic protein is modified by O-glcnac or is very likely to be modified by O-glcnac. O-glcnac/OGA/OGT can be viewed as a master, master regulator of almost all cellular function.

So what does this have to do with the topic? The substrate for O-glcnacylation, which is UDP-GlcNAc-- is a direct by product of glucose, and more specifically, glycolytic metabolism. In otherwords, there is a very direct link between sugar consumption and metabolism, regulation of the proteome, and disease potential through O-GlcNAc.

How could disease be possible though disturbing sugar metabolism? Well, the O-GlcNAc modification is known to regulate the function, localization, and a myriad of other things of some very, very interesting proteins.

For example, O-GlcNAc is a master regulator of writing your epigenetic code--both DNA methylation and regulation of histone dynamics:

http://www.ncbi.nlm.nih.gov/pubmed/21045127 (regulation of the histone code by O-glcnac)
http://www.cell.com/molecular-cell/abstract/S1097-2765(12)01055-6 (regulation of DNA methylation dynamics via o-glcnac)

It stands to reason that overtime, excess sugar consumption could somehow perturb how your genes are expressed, and that could possibly be through the regulation of the epigenetic code through O-glcnac (again a by product of glucose metabolism). In fact, the evidence is increasingly pointing in this direction, and it could very well be why altered sugar metabolism is a very common observation for major diseases like cancer, diabetes, alzheimer's, and heart disease.

In fact, here's a review on O-glcnac signaling in the cardiovascular system
http://circres.ahajournals.org/content/107/2/171.abstract

Also may be of interest:
http://www.ncbi.nlm.nih.gov/pubmed/20410435

Heart complications in diabetics and pre-diabetics is a well known and observed phenomenon and the link between the two could very well be sugar, and more specifically on a molecular level this could be via O-glcnac. There is a lot of very interesting emerging evidence linking sugar consumption to major disease on the molecular level.

Interestingly though, during times of stress (ischemia/reperfusion injury), maybe massive doses of sugar could be used in a cardioprotective manner since stress directly signals for the upregulation of the metabolic pathway that feeds into O-GlcNAc (but too much of a good thing overtime may be bad):

http://www.ncbi.nlm.nih.gov/pubmed/24630721
I wouldn't be surprised if 20-30 years from now we will have shown that sugar is in fact more damaging to your health than consumption of saturated fats.

 

[lisab]

Wow. Great information, GNW!

 

[Astronuc]

And if one needs more - http://www.ncbi.nlm.nih.gov/books/NBK1908/

Historical Background and Overview of Glycobiology - http://www.ncbi.nlm.nih.gov/books/NBK1931/

The O-GlcNAc Modification - http://www.ncbi.nlm.nih.gov/books/NBK1954/

 

[lavinia]

Sugar is directly linked to reprogramming the entire way your cell functions (cancer, diabetes, AZ are all characterized by abnormal glucose metabolism/consumption). I know I sound like a crazy person for constantly talking about the O-glcnac modification on these forums, but it is absolutely a thing of beauty--and I wouldn't be surprised that years from now it would be Nobel worthy.

First, some background. Protein physiology is almost always shown in cascade cartoons as being like on/off switches via phosphorylation, however it is becoming increasingly clear that this is a grossly oversimplified model. The O-glcnac modification (which is the addition the sugar N-acetylglucosamine) occurs on proteins at Ser/Thr residues in proteins and many times these Ser/Thr residues are the same exact sites where protein phosporylation occurs. If you can start to see the bigger picture, the significance of O-glcnacylation can not be understated. It behaves as a 'cap' almost to block sites from being phosphorylated on proteins. In otherwords, our models of protein physiology are vastly oversimplified because you are ignoring the fact that proteins should have multiple sites for not only phosphorylation but also for O-glcnacylation (plus mutiple combinations thereof between the two) and need to include some sort of extremely complex cycling mechanism between both phosphorylation addition/removal and addition/removal of O-GlcNAc.

Consider how many hundreds, if not thousands, or kinases and phosphatases that exist in order to regulate the phosphorylation status of the proteome. Contrast that to the O-glcnac modifcation which is controlled by only 2 enzymes--OGT which adds it to proteins and OGA which removes it, that's it (why it's mechanism and discovery is so beautiful). We now know that almost every cytosolic protein is modified by O-glcnac or is very likely to be modified by O-glcnac. O-glcnac/OGA/OGT can be viewed as a master, master regulator of almost all cellular function.

So what does this have to do with the topic? The substrate for O-glcnacylation, which is UDP-GlcNAc-- is a direct by product of glucose, and more specifically, glycolytic metabolism. In otherwords, there is a very direct link between sugar consumption and metabolism, regulation of the proteome, and disease potential through O-GlcNAc.

How could disease be possible though disturbing sugar metabolism? Well, the O-GlcNAc modification is known to regulate the function, localization, and a myriad of other things of some very, very interesting proteins.

For example, O-GlcNAc is a master regulator of writing your epigenetic code--both DNA methylation and regulation of histone dynamics:

http://www.ncbi.nlm.nih.gov/pubmed/21045127 (regulation of the histone code by O-glcnac)
http://www.cell.com/molecular-cell/abstract/S1097-2765(12)01055-6 (regulation of DNA methylation dynamics via o-glcnac)

It stands to reason that overtime, excess sugar consumption could somehow perturb how your genes are expressed, and that could possibly be through the regulation of the epigenetic code through O-glcnac (again a by product of glucose metabolism). In fact, the evidence is increasingly pointing in this direction, and it could very well be why altered sugar metabolism is a very common observation for major diseases like cancer, diabetes, alzheimer's, and heart disease.

In fact, here's a review on O-glcnac signaling in the cardiovascular system
http://circres.ahajournals.org/content/107/2/171.abstract

Also may be of interest:
http://www.ncbi.nlm.nih.gov/pubmed/20410435

Heart complications in diabetics and pre-diabetics is a well known and observed phenomenon and the link between the two could very well be sugar, and more specifically on a molecular level this could be via O-glcnac. There is a lot of very interesting emerging evidence linking sugar consumption to major disease on the molecular level.

Interestingly though, during times of stress (ischemia/reperfusion injury), maybe massive doses of sugar could be used in a cardioprotective manner since stress directly signals for the upregulation of the metabolic pathway that feeds into O-GlcNAc (but too much of a good thing overtime may be bad):

http://www.ncbi.nlm.nih.gov/pubmed/24630721
I wouldn't be surprised if 20-30 years from now we will have shown that sugar is in fact more damaging to your health than consumption of saturated fats.

While I am not a biologist and can not comment on these papers myself, it seems from what you have said that the toxic effects of sugar on the heart are known in diabetics but are only speculated upon for normal individuals.

 

[lavinia]

I sent one of the referenced papers to a friend who during his career was a physician, medical researcher, and a renowned molecular biologist. The paper talks about heart cell death in hyperglycemia. Here is his reply.

"
Yeah this paper discusses HYPERGLYCEMIA, and abnormal condition that results in glycosylation of a number of proteins that are not normally glycosylated, and myocardial cell death. However, in a normal individual, blood glucose levels are kept at about 100 mg%, and the glucose that is imported into myocardial cells is essential for myocardial function. Glucose is the main source of ATP and NADPH production in the cell, and both molecules are required for myocardial contraction. So, while this paper may illuminate a pathological effect of diabetes, it says nothing about normal heart function in a normoglycemic individual.

Put it another way: you could completely starve a normal individual for carbohydrates including sugar, and their blood glucose would still be 100 mg% and myocardial cells would still get the same amount of glucose."

Here is his follow up reply.

"Incidentally - here's what happens if you completely deprive someone of glucose: First, glycogen stores in the liver and muscle are broken down to give glucose - glycogen is a polymer of glucose and is stored in these sites. Carbohydrate loading by marathon runners is done to maximize these stores, as they are the quickest way to get glucose into the blood. Once those stores are exhausted, the process of "gluconeogenesis" becomes increasingly activated. This process allows amino acids from muscle and other proteins to be converted to glucose. Fats can also be substrates for gluconeogenesis, but that process involves far more steps. The bottom line here is that a normal individual has jealously guarded homeostatic mechanisms for maintaining blood glucose levels.

If blood glucose levels drop severely for any reason (raging bacterial infection, an overdose of insulin, or other causes), the physiologic alarm bells go off - heart rate increases dramatically along with respiratory rate, and a variety of hormones, like cortisol and adrenaline, that raise blood glucose, are poured into the bloodstream. Since the brain requires glucose for normal function, extended periods of severe hypoglycemia can lead to coma and death or permanent brain damage.

The bottom line: glucose is the central molecule in intermediary metabolism and is essential for life. Your body will do anything and everything to maintain normal levels."

 

[Astronuc]

"Incidentally - here's what happens if you completely deprive someone of glucose: First, glycogen stores in the liver and muscle are broken down to give glucose - glycogen is a polymer of glucose and is stored in these sites. Carbohydrate loading by marathon runners is done to maximize these stores, as they are the quickest way to get glucose into the blood. Once those stores are exhausted, the process of "gluconeogenesis" becomes increasingly activated. This process allows amino acids from muscle and other proteins to be converted to glucose. Fats can also be substrates for gluconeogenesis, but that process involves far more steps. The bottom line here is that a normal individual has jealously guarded homeostatic mechanisms for maintaining blood glucose levels.

One often smells ammonia on the breath as a result. This is what I experienced in heavy exertion on my bicycle.