My name is Nick and I am currently doing my PhD in physiology with an emphasis in muscle physiology. Welcome to my exercise science blog. Unlike a lot of fitness blogs out there, this one is unique because it is backed by true science. You will find only articles that have been peer reviewed and published in top tier science journals on this blog. For the fast easy read, just read the bold type. If you have any questions do not hesitate to ask me. I am at your disposition for any advice in exercise or just basic physiology. This is not a progress blog to benefit myself but rather to share some of my knowledge and expertise with you that I have gained over my years dedicating my career to exercise science. If I do not know the answer, I will do my best to search through the journals to find it for you. Although I am in biomedical research, I am not a licensed medical professional so please consult a physician before entering any exercise or nutrition program.
February 16, 2012
Where your body deposits fat matters in regards to insulin resistance and future cardiometabolic risk. Here is a figure from a brand new study published by my doctoral adviser in Obesity. Getting around the ugly statistical box plots, what it means to you is simply that subcutaneous thigh adipose tissue appears to show a protective effect when it comes to insulin resistance (Dr. Amati uses Rd in this case, which is rate of glucose disposal, as a marker of insulin sensitivity). The higher you are on the scale, the more sensitive your periphery is to insulin. The worst marker of insulin sensitivity, and what scientists can deem as the dangerous area to store fat, is the visceral abdominal adipose tissue. These results are all regardless of age and gender.
Here we see again the apple vs. the pear story in how one stores fat depots where in this case, the pear seems to win, or at least, be favored.
Finally, we’ve come to the end of sugar month when I will now gather all of the thoughts to bring you the key points of what we know now in the scientific community in regards to sugar.
Sugar when given in large amounts can have deleterious effects. The key to this sentence are the words in bold.
The effects are essentially on hepatic lipids, plasma lipoproteins, and hepatic insulin sensitivity.
The effects are related to fructose more than glucose.
The effects of high-fructose corn syrup and sucrose are the same.
The effects of fructose can be attenuated by exercise.
It is important to note that intervention studies, that is to say, studies over long periods of time are necessary and needed to truly elucidate whether or not increases in sugar are harmful over a substantial period of time. Until these are accomplished, it is difficult to conclude true health consequences of sugar ingestion.
Hope you learned something from all of this and that you can apply the knowledge given here to better your health and lives.
Last April, there was a very popular article published in the New York Times about how sugar is toxic to the body. Although it is not entirely scientifically sound, it is still a well written piece, stemming from the original, and hugely popular, video from Dr. Robert Lustig posted on YouTube back in 2009.
Dr. Lustig publicly proclaims that sugar is indeed toxic to the body as that of tobacco products or alcohol. This acclimation began with a publication in the American Dietetic Association journal back in 2010 when Dr. Lustig wrote an entire detailed review on fructose having similar properties to ethanol. In summary, Dr. Lustig states that fructose has deleterious effects on the liver similar to that of ethanol in that it:
Drives de novo lipogenesis, resulting in dyslipidemia, steatosis, and insulin resistance.
Increases the amount of reactive oxygen species which in turn increases the risk for liver cell damage.
Activates reward centers in the brain by blocking leptin and promoting sensations of hunger, which contributes to a positive feedback pathway for continuous ingestion of food, even when you’re not hungry.
Although these consequences of consuming excess sugar are possible, Dr. Lustig also provides two “antidotes” to combat the harmful liver effects from fructose:
Exercise: which increases hepatic TCA cycle maximal velocity leading to a process of biochemical events that will eventually provide less substrate for the creation of triglycerides. In addition, improving the activity of mitochondrial proteins involved in promoting insulin sensitivity.
Fiber: by reducing glycemic load and rate of carbohydrate absorption, fiber reduces the content of energy from the food the liver has to metabolize which in turn again, reduces triglycerides and improves insulin sensitivity. Also, fiber is well known to increase satiety which would reduce consumption of more sugar.
Dr. Lustig also adds that although fructose is considered a carbohydrate, it is metabolized more like fat substances.
More recently (as of last week), Dr. Lustig is back at it again, publishing a comment article in Nature where he states some dramatic proposals in regards to fighting the war on increased sugar consumption. Again he drives home the point that sugar is analogous to consuming alcohol claiming that it is unavoidable in society, toxic, has the potential for abuse and creates a negative impact (metabolic syndrome) on society. There is even a link between sugar consumption and increases in the likelihood of cancer. He then proposes that there should be a tax on any processed foods that contain any form of added sugars including soda, juice, sports drinks, and chocolate milk. Does this seem extreme to you? Would this really reduce consumption? Statistical models show that for this to have an impact, companies would have to double the prices of all of these drinks to reduce intake. Furthermore, Dr. Lustig states that there should be a limit on the availability of these products, such as limiting the hours retail stores are open to sell these products, regulating the location and amount of retail markets, and setting a limit as to who can legally purchase these items. Yes, that’s right, Dr. Lustig feels you should be at least 17 years old to purchase drinks with added sugar.
Okay, I understand the detrimental effects of sugar on the body and you’ve seen for the past month numerous studies showing them, but accomplishing all of these does not seem feasible in the U.S. High-fructose corn syrup (HFCS) is not the sole culprit for the increase in obesity and Type 2 diabetes in the United States. This notion was stated by John White in an article back in 2008 on the content of HFCS where he goes on to break some common misconceptions about this sweetener and sucrose. As stated in the first week of sugar month, HFCS has a similar content to that of sucrose; 50% glucose and 50% fructose. The only real difference is, and the reason of the stigmatic popularity to brand this sweetener as the reason for the obesity epidemic, is that it is cheaper for companies to use in their products. White states that HFCS is not predictive of the rise in US obesity due to these conclusions:
HFCS has the same sugar composition of other “benign” fructose-glucose sweeteners such as sucrose, honey, and fruit juice concentrates.
Increased caloric intake since 1970 was not due to added sugars (including HFCS) but rather due to increased consumption of all caloric nutrients, especially fats, flour, and cereals
Fructose-glucose sweeteners are all metabolized through similar pathways regardless if you ingest them from fruit, sodas, or fruit drinks.
Therefore, in White’s view, switching back to sucrose instead of HFCS in products would have, “no change in basic metabolism and no changes in the rates of obesity” (since sucrose and HFCS are essentially the same two monosaccharides). ”The one change that consumers would notice is higher prices as sucrose is substituted for the less-expensive HFCS.”
Tomorrow is the conclusion of sugar month but for now I would like to know what some of you think about this post. Do you think sugar is truly as toxic as Dr. Lustig states and should we take such drastic actions in limiting the consumption and availability of these sugar additives?
Continuing with fructose, our focus now shifts towards the effects on the liver. Some of you might have heard of non-alcoholic fatty liver disease, which is the accumulation of fat inside the liver that eventually leads to inflammation, scarring, and finally, cirrhosis (when the scar tissue replaces the actual liver cells). Through the mechanisms of storing fat outside of normal fat depots (what we call ectopic fat depositions), scientists believe this creates a milieu of metabolites that eventually leads to insulin resistance and, subsequently, Type 2 Diabetes. I’ll keep it short this time.
If you look at Figure 1, you can see that ingesting large amounts of fructose (in this case it was equal to 4L of soda/day, yikes) causes an increase in de novo lipogenesis from the liver. It is also known to increase fasting triglycerides, which this study suggests a correlation between the two. I know this large amount is not comparable to everyday ingestion for a normal person but nonetheless it shows you the possibility.
The second figure is another study that shows increases in ectopic lipids (IMCL = intramyocellular lipids and IHCL = intrahepatocellular lipids) as well as triglycerides.
In regards to insulin resistance, the third figure from another study actually done here in the department of physiology shows indeed, even fructose overfeeding decreases hepatic insulin sensitivity.
Finally, the last figure is a proposed pathway by Prof. Luc Tappy on how fructose can lead to insulin resistance through several different mechanisms.
Figures adapted with aid of Prof. Luc Tappy MD, PhD
Fructose, friend or foe? It can be so beneficial to endurance athletes but so detrimental to the sedentary person. These findings may alarm you.
Introduction: As stated previously during sugar month, large fructose ingestion is linked with an array of health problems. In this case, researchers link it to the metabolic syndrome, which consists of insulin resistance, dyslipidemia, abdominal obesity, and elevated blood pressure. The metabolic syndrome often precedes the development of Type 2 diabetes. Some of these effects are not found with glucose or diets consisting of starch. Fructose and glucose metabolism differ and one of the consequences is depletion of ATP and production of inflammatory mediators. The breakdown eventually leads to the production of uric acid, which may have a role in insulin resistance. Therefore, the researchers are trying to use a drug, allopurinol, as a way to reduce uric acid and see if this can reverse the symptoms of metabolic syndrome after fructose consumption.
Methods: Participants were 74 males who ingested 200g daily of fructose sipped throughout the day for a total of 2 weeks. One group received the drug allopurinol and the other did not.
Results: The following showed significant differences from baseline in regards to fructose ingestion:
Increase in ambulatory blood pressure with subtle greater increases in diastolic blood pressure throughout the day (number of participants who fit the criteria of metabolic syndrome for this went from 9 at baseline to 21)
Mean increase in fasting triglycerides
Reduction in HDL cholesterol
Increase in patients with fasting glucose meeting the criteria for metabolic syndrome ( >5.5 mmol/L)
Increase in fasting plasma insulin
Worsening of liver function tests
In regards to the group that consumed the drug (allopurinol) to decrease uric acid there were significant changes found to:
Protect against increases in systolic and diastolic blood pressure as well as mean arterial pressure
Protect against metabolic syndrome (32% participants had it before and only 34% after as compared to the fructose only group at 19% to 44% after two weeks)
Discussion/My input: The first thing you are probably thinking is, “Nick, who would drink 200g of fructose per day, this study is not practical.” Well, here is an alarming fact; the upper quintile of Americans consume more than 110 g of fructose daily either as additional sugar or as high-fructose corn syrup. That is pretty close and these changes happened in only 2 weeks! As far as the drug, it may be something included in the future to combat the metabolic syndrome; however, these results cannot be related to obese individuals or even women. The researchers state that fructose metabolism can vary between genders. Once again, fructose might not be the sole reason for the obesity epidemic, but it does lend credence to that notion.
The remainder of “sugar month”, for lack of a clever name, is going to be dedicated to mostly research about fructose. Therefore, it is appropriate that I also give you an introduction to High Fructose Corn Syrup (HFCS) and some background on fructose metabolism. Once again, we’ll keep it simple.
Fructose is found naturally in fruits and honey. It has somewhat of a low glycemic response in that it does not elicit as high of insulin spikes postprandial as other sugars. In fact, sports products that contain fructose are what are responsible for some of the stomach discomfort that endurance athletes experience upon ingesting these drinks during physical activity. HFCS can be a somewhat misleading term in that it is not entirely just fructose. HFCS is extracted from the starch (Amidon) in corn to make a glucose syrup. From this syrup, half of it is made into fructose (because pure glucose does not have a pleasant taste) and the other half is mixed with glucose. Thus, HFCS has a similar composition as sucrose (50% glucose, 50% fructose). This is summarized in the first figure.
As shown in Figure 2, the metabolism of fructose is similar to glucose in that it involves the GLUT2 transporter. Fructose metabolism is not dependent on insulin secretion. The fate of fructose upon ingestion within the organ systems can be seen in Figure 3. In summary, the effects of fructose on the body from numerous studies show that:
Long term fructose ingestion can induce metabolic disorders
In rodents: a high fructose/sucrose diet leads to obesity, insulin resistance, diabetes, dyslipidemia, and high blood pressure.
In humans: high fructose/sucrose diets lead to hypertriglyceridemia
As stated yesterday, increases in HFCS parallel the increases in obesity in the United States but it is unknown whether or not this is the sole factor. Now that you have the necessary background of the sugars and how this corresponds to metabolism, the rest of sugar month will be science articles convincing you that increased ingestion may or may not be a factor in obesity and diabetes.
So I told you that I’m dedicating this month to all about sugar and its effects on health. What I have for you is a plethora of studies and the aid of one of the leaders in the world on sugar metabolism studies in humans, Professor Luc Tappy. Before we begin, I’ll start with a simple introduction because I know those not in the sciences like science simple (and to avoid any pedantic writing).
Sugars in their simplest forms can be classified as the monosaccharides. We’ll stick to three of them: glucose, fructose, and galactose. Combining them together into disaccharides such as glucose + fructose gives you sucrose (table sugar) or glucose + galactose gives you lactose (what is found in milk). Each have different properties and their own role in metabolism. I’ve included a figure on the breakdown of carbohydrates and the absorption of these three monosaccharides.
The history of increases in sugar consumption began during the period of the Crusades when it was considered white gold. As you can see in the second figure, there was a large increase in sugar around 1850 which corresponds to an eventual (100 year) subsequent increase in obesity (the black dots) up until present day. This leads scientists to attribute increases in sugar as one of the main factors for the increase in obesity. However, is this really the sole cause?
The third figure shows the increase in sugar consumption per capita since 1986. It is important to note that this does not include consumption of the less expensive sweetener, high fructose corn syrup (more on this tomorrow). Finally, if we focus just on the U.S. you can clearly see in the last figure the trend of an increase in sugar consumption and a switch from ingesting sucrose to more high fructose corn syrup. Is this cheaper alternative really that bad for your health?
What I hope for you to take away from this month is the pathophysiological effects of a diet containing high amounts of sugar, specifically fructose, and how this potentially could have lead to the obesity epidemic and the relationships with diabetes.
Here is a very interesting figure published in Diabetologia last month showing that across all age ranges, men (the black dots) develop Type 2 Diabetes at a lower BMI than women. The means were 31.83 kg/m(2) (SD 5.13) in men and 33.69 kg/m(2) (SD 6.43) in women polled from 51,920 men and 43,137 women. Now that’s a strong sample size. It is very important to note that it is only Caucasians that were reported here and this may be different for other ethnic groups.
Epidemiologists from the School of Medicine at The University of Texas Health Science Center San Antonio reported data showing that diet soft drink consumption is associated with increased waist circumference in humans, and a second study that found aspartame raised fasting glucose (blood sugar) in diabetes-prone mice.
“Data from this and other prospective studies suggest that the promotion of diet sodas and artificial sweeteners as healthy alternatives may be ill-advised,” said Helen P. Hazuda, Ph.D., professor and chief of the Division of Clinical Epidemiology in the School of Medicine. “They may be free of calories but not of consequences.”
Diet soft drink users, as a group, experienced 70 percent greater increases in waist circumference compared with non-users. Frequent users, who said they consumed two or more diet sodas a day, experienced waist circumference increases that were 500 percent greater than those of non-users.
Sphingomyelin (SM) is one of the major phospholipids (components of the plasma membranes of cells) of the lipid microdomains. These are important regulators in the control of lipid entry into storage form, the lipid droplet. In this study, researchers looked at an enzyme of this SM that you can see in this figure, SMS2. Why is this important? This is why: deficiency in this enzyme prevents HFD-induced fatty acid uptake and lipid droplet formation, which would lead to fatty liver, obesity, and insulin resistance. We want this enzyme inhibited or downregulated in the body.Therefore, you are potentially looking at the next pharmaceutical target for the treatment of obesity and Type-2 diabetes by regulating the lipid domains on the plasma membranes of cells and subsequently, storage of lipid (fat).