Research Blog

Losing Weight: Control Quality, not Quantity

lemons and oranges healthy fruit


A program that encouraging drinking water, eating whole foods and 30 minutes of daily walking significantly increased participants’ health.





A study published in the January issue of Advances in Preventive Medicine found that participants in a health program focused on eating healthier calories rather than less calories showed significant improvement in health parameters and weight loss (Short-Term Effectiveness of a Lifestyle Intervention Program for Reducing Selected Chronic Disease Risk factors in Individuals Living in Rural Appalachia: A Pilot Cohort Study, 2014. David Drozek, et al.).

The program utilized the Complete Health Improvement Program (CHIP), which is a community lifestyle intervention program. Most of the program sessions met 4 times a week for 4 weeks. The individual sessions consisted of an instructional video, a group discussion and an exercise component. The CHIP program focuses on encouraging participants to consume whole foods ad libitum; foods such as fresh fruits, vegetables, whole grains, legumes and nuts. Participants strived to consume less than 10 teaspoons of sugar, 50 mg of cholesterol and 2000 mg of sodium. Furthermore, participants were instructed to consume at least eight glasses of water and keep fat content below 20% total calories. Study participants were self-selected from rural Ohio.

The participants showed significant reductions in body mass index, systolic and diastolic blood pressure and fasting blood levels of total cholesterol, low-density lipoprotein, and glucose. Those participants who were the most at-risk showed the greatest improvements in the health biomarkers measured.

As our overloaded healthcare system shifts toward preventive care, as directed by the Affordable Care Act, it will be important to find simple ways to improve health. This study highlights easy steps one can take to enhance his or her health. Furthermore, the program was relatively inexpensive and was effective in a rural community with high poverty and obesity. The medical community must play a pivotal role in inspiring healthier lifestyles in the population it serves. 

Our Genetic Code determines How We React To Training

genetics, woman, hispanic, weights, working out, exercise, training, GEAR,


A new study hopes to explore the genetics of the training response. This research will identify genes that predict how one’s body will react to training. This information will be useful for both the competitive athlete looking to increase performance and patient trying to regenerate fitness.


Along with motivation, coaches encounter two additional traits that predict an athlete’s future success: innate talent and ability to react to training.  These two traits generate four different types of athletes. An athlete with limited innate talent and a limited ability to react to training, unfortunately, has little potential in athletics.  The second type of athlete has great innate talent, but limited ability to react to training. These are the athletes in high school that seem destined for superstardom as a freshman, but fail to show significant improvement over the course of their athletic careers. These athletes are often criticized for lacking the will to capitalize on their potential, but it is easy to emphasize with the personal frustration that comes about when training fails to bring improvement. The third type of athlete lacks innate talent, but reacts strongly to training. These athletes may be able to reach the innate athlete with limited ability to adapt to training, but they must put in a lot more work. Because training is rewarding to the third type of athlete, they usually train hard, but due to limited innate ability, often fail to reach the pinnacle of their sport. It is the fourth type of athlete, with a mix of innate talent and an ability to react to training, that makeup most of the superstars of athletics.

Innate talent is relatively easy to determine. Either one has it or they do not.  The ability to react to training is harder to determine.  To test, one must actually participate in a training program. To complicate matters, an individual may be predisposed to react better to a specific type of training.  For example, one may be able to build anaerobic muscle by lifting weights, but fail to develop aerobic capacity by swimming. Of course, the situation could also be reversed. What if one could test their ability to respond to different types of training?

In 2012 a team at the University of Miami set out to lay the foundation for a genetic test to determine an individual’s ability to adapt to training. The study is called the Genetics of Exercise and Research (GEAR). Our genes determine traits ranging from height to predisposition to cancer.Thus, it is not far fetched that genes also can determine one’s adaptability to exercise.David Epstein highlights the GEAR study for its potential to predict athletic performance in his bestselling book, The Sports Gene. This research would be useful not just for athletes, but also patients looking for programs to increase their fitness. Some of the molecular factors that were proposed by investigators in the GEAR study to play a role in defining innate adaptability to training are shown in the figure below.

This figure shows molecule markers in different physiological systems that may define innate adaptability to training.  These markers were proposed by investigators in the GEAR study in 2012.

One group the GEAR study initially looked at for genetic markers was a multi-ethnic cohort of women (Genomic Signatures of a Global Fitness Index in a Multi-ethnic Cohort of Women, 2013. Rampersaud E, et al.). This study looked at composite fitness improvement over a variety of fitness tests. The 12-week training program that the women participated in consisted of both cardiovascular and resistance training. Participants were all sedentary in at least the 6 months prior to the fitness program and ranged in age from 18 to 65. The subjects were divided into quartiles based on improvement in composite fitness score. Those in the top quartile were labeled high responders and those in the bottom quartile were labeled low responders.  

Interestingly, the expression of 39 unique genes were found to differ between the high and low responders at baseline. The pathways implicated included oxidative phosphorylation (generating ATP fuel using oxygen and glycolysis products) and lipolysis (breaking down fat molecules). Furthermore, a gene that has been shown to predict VO2 Max following training was found to be elevated in the high responders at baseline. The gene is an androgen chaperone protein regulated by insulin. Two genes up-regulated in low responders play a role in regulating platelet responsiveness. Additional genes involved in inflammation, immunity and angiogenesis (the creation of new blood vessels) were found to differ in the low and high exercise responders.

In the next several years, the GEAR study will provide preliminary research for additional genes to investigate. It will be fascinating to see how our increased knowledge of the genetics of adaptability to exercise changes how we approach competitive athletic training and fitness conditioning.


Workload Mechanics of Nordic Skiing

todd lodwick, cross country skiing, nordic, sochi


US Cross Country Skiing Olympian Todd Lodwick (right) was the American flag bearer at 2014 Winter Games in Sochi. A study finds that increases in double pole cross country ski work rate come from the legs, not the arms.



Cross country skiing is unique in that it requires enormous aerobic capacity. Aerobic capacity not only is a requirement of cross country skiing, but it also is a powerful predictor of nordic performance. In fact, a study done in 1991 found that VO2 Max, a measure of aerobic capacity or, more specifically, the maximum amount of oxygen that can be consumed by a subject during strenuous exercise, can predict the success of elite cross country skiers. VO2 Max could predict if an elite cross country skier was less successful, more successful or world class (Maximal oxygen uptake as a predictor of performance ability in women and men elite cross-country skiers, 1991.  Ingjer F).

In cross country skiing there are two primary techniques of movement: diagonal stride and double poling. Diagonal stride (see Todd Lodwick above) is used on uphill sections and requires mostly leg power. On the other hand, double poling is done on flat terrain and utilizes a combination of leg power and arm power.  The physiological mechanics of double poling were investigated in a study published in the Scandinavian Journal of Medicine & Science in Sports (Metabolic and Mechanical involvement of arms and legs in simulated double pole skiing, 2013. Bjarne Rud, et al.).

Double pole cross country skiing poses a problem for the arms. The arms rely on increased blood pressure during exercise, but when the legs are working their increase in circulation drops the blood pressure. Furthermore, the legs maintain a high arterial-venous oxygen difference that is generally not produced by working arms. So when a nordic skier increases his work rate while double poling, which limbs take up the additional work?

Subjects on a cross country 
skiing ergometer that mimics
cross country skiing.

The answer appears to be the legs. Bjarne Rud and colleagues found that when recreational cross country skiers were put on a machine that mimics cross country skiing, a cross country ergometer, the subjects increased work rate using their legs. The ergometer used by the researchers is pictured to the left. The subjects used the cross country skiing ergometer at a low and moderate work rate. A variety of physiological parameters were measured from the eight subjects.

One of the parameter measured in the subjects was the degree of motion of different joints. The degree of motion of the shoulder, elbow, knee and trunk were each measured. The knee was the only joint that showed a significant difference in range of motion between low and moderate work rate. The range of motion of the knee significantly increased when the work rate was increased from low to moderate on the cross country ski ergometer. The figure below shows the results of measuring the degree of motion in the shoulder, elbow, knee and trunk joints.  

Shoulder, elbow, knee, and trunk ranges of motion during low and moderate work rate double pole ergometer skiing. *P < 0.05 between work rates; n = 8.

In addition, the researchers measured blood flow and VO2 in the subjects at rest, at a low work rate and at a moderate work rate. Blood flow increased significantly in both the arm and leg when the subject work rate increased from a low to moderate work rate. However, VO2, which is a measure of oxygen consumption, showed a significant increase in the legs relative to the arms at moderate exercise. The figure below shows this blood flow and VO2 data.

Variables during double pole ergometer skiing. Arm and leg blood flow (a) and oxygen uptake (VO2) (b) at rest and low and moderate (Mod) work rates. *P < 0.05, between arm and leg; †P < 0.05, between work rates. BP; n = 8 or as indicated during rest and moderate work rate for VO2 and blood flow.

The researchers also investigated potassium and lactate balance. Potassium is released when the muscles and motor neurons repolarize between contractions.  The arms were found to have a net release of potassium at a low and moderate work rate. This suggests that the muscle fibers are firing to fast for the Na+/K+ ATPase pumps in the sarcolemma and neuromuscular junction to recover the released potassium. The legs had a neutral potassium balance. With regards to lactate, the arms had a negative lactate balance at a low and moderate work rate. The legs had, on the other hand, a positive lactate balance at a low and moderate work rate. Recall that lactate is a product of anaerobic metabolism.  Lactate can be used as fuel if sufficient oxygen is present to oxidize it. Thus, the legs burn the lactate that the arms were unable to oxidize.

All this data suggests that the arms are at maximal aerobic capacity under a low work rate during double poling. It is important to note that the subjects were recreational skiers, and this conclusion may not hold with elite cross country skiers. In addition, the data was collected by subjects on an ergometer in a lab. One can only speculate at how these results would change if the experiments were performed on snow with actual cross country skis. 

What is EPO?

lance armstrong, epo, cycling, doping, blood doping


EPO is a well-known performance enhancing drug that is a common form of blood doping. In 2013, disgraced cyclist Lance Armstrong notoriously admitted to using EPO throughout his career.




Following rampant use by endurance athletes, EPO has earned a reputation as a potent performance enhancing drug. EPO is injected into the blood, a common form of blood doping, to increase the red blood cell count and metabolic factors necessary for aerobic exercise. Its popularity with endurance athletes is a reflection of its powerful effects on performance.  EPO is banned by most sports governing bodies. However, EPO naturally plays a role in regulating a myriad of physiological functions and has recently been found to be of clinical importance.

So what is EPO? EPO is short for erythropoietin. Erythropoietin is responsible for triggering erythropoiesis, the production of new red blood cells. The history of its discovery is rather interesting, and was described in a recent review in Cold Spring Harbor Perspectives in Medicine (Erythropoietin, 2013.  Bunn HF).  

Erythropoiesis in response to altitude was discovered in 1890 when Viault observed that his red blood cell count increased dramatically after two weeks in the mountains of Peru. It was not until 1950 that Reissmann and Ruhenstroth-Bauer showed conclusively that hypoxia (low oxygen) conferred erythropoiesis via a factor in the blood. They proved this by connecting a pair of rabbits at the capillary level by overlapping flaps of their skin.  When one rabbit breathed hypoxic air and the other breathed normoxic (sea level air), the result was both rabbits dramatically increased red blood cell production. By 1964, researchers had found that EPO was produced primarily in the kidneys. Actual human EPO was not isolated and purified until 1977. The EPO amino acid sequence was determined in the 1980s.

Regulation of red cell production by Epo. (A) Decreased oxygen delivery to specialized cells in the kidney results in increased expression and secretion of Epo, which circulates in the plasma and stimulates marrow progenitors, thereby increasing red cell production. If the increase in red cell mass relieves the hypoxic signal, Epo expression is down-regulated. (B) Plasma Epo levels (milliunits/mL) in patients with different types of and degrees of anemia and in those with primary erythrocytosis and secondary erythrocytosis. HIF, hypoxia inducible factor; PCV, polycythemia vera.

How is EPO regulated in the body?  EPO is not directly regulated by hypoxia. A factor called Hypoxia-Inducible-Factor (HIF) turns on EPO transcription in response to hypoxia. As a side note, HIF stabilizers are another banned performance enhancing drug. HIF is extremely unstable and therefore undetectable in cells when one is breathing air with sea level oxygen concentration (21%). When oxygen levels are lowered to hypoxic levels, HIF is much more stable due to deactivation of the HIF-specific ubiquitination protein (which labels HIF for degradation). Under hypoxic conditions, HIF binds to the EPO gene and stimulates transcription of EPO mRNA. EPO mRNA is then translated into the EPO protein by ribosomes. In the kidney, the primary location for EPO synthesis, the HIF subset HIF-2 is responsible for triggering EPO mRNA transcription. EPO then stimulates red blood cell production in the bone marrow by binding to its receptor there, EpoR. The figure above shows this negative feedback loop. 

In addition to its role in regulating erythropoiesis, EPO plays a part in regulating a number of other physiological processes. A review published last year highlights the diverse functions of EPO (Epo and Non-hematopoietic Cells: What Do We Know? 2013. Ogunshola OO and Bogdanova AY).

EPO bound to receptor EpoR, biochemical structure

In the nervous system, EPO serves as a neurotrophic factor and provides neuroprotection. Neuroprotection refers to protecting existing neurons from death due to oxidative stress, ischemia or a variety of neurodegenerative diseases such as Alzheimers. Neurotrophic factors promote regeneration of neurons through neurogenesis following an insult such as stroke. Likely as a result of these effects on the brain, EPO has been shown to be a potential therapy for stroke, depression and neurodegenerative disease in animal studies. Unfortunately, limited human clinical studies with cerebral EPO therapy have produced mixed results.

EPO impacts the heart, endothelium and pancreas. EPO is necessary for heart development. EPO has been found to increase the contractile force, but not rate, of the hearts myocardium. EPO attenuates inflammation in the heart. In the endothelium, EPO promotes blood vessel repair. Furthermore, EPO stimulates vessel proliferation and prevents apoptosis of existing endothelial cells. EPO has been found to help restore the function of beta cells in the pancreas of diabetic mice. EPO overexpression in mice has also been shown to increase insulin sensitivity and lower body weight.

In 1989, the FDA approved a synthetic form of EPO, termed Epogen, developed by Amgen for treating anemia. The utility of EPO therapy for patients with pancreatic, cardiovascular or nervous diseases has been debated. Human trials so far have proved inconclusive. Nonetheless, researchers believe EPO has potential to treat a variety of diseases from depression to diabetes. In summary, we use EPO for numerous physiological functions. As anti-doping agencies continue to crack down on blood doping, EPO may become better known as a clinical therapeutic, rather than a notorious performance enhancing drug. In the meantime, just thank EPO for allowing you to exercise at sea level and simply survive at altitude.

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