By Dr. Mark Miller

A recent report at the Experimental Biology meetings in 2012 by Reidy et al., is worthwhile because it challenges the monocular view of the importance of single protein sources in sports nutrition. The latter concept has become pervasive despite or because of its simplicity. Perhaps it is time to recap the various factors at play here and take a moment to consider the history behind where we are now. Valuable lessons may have been lost with the passage of time.

Protein in sports performance has its roots in infant nutrition, which is a state of remarkable anabolic needs. By understanding the evolution of infant nutrition one can better appreciate where we are today in sports nutrition. Firstly, it is important to note that all mammalian milks are protein blends, they are not a single protein source and even broad classifications are comprised of numerous protein forms. The first major breakdown is the amounts of casein and whey. The relative amounts of casein and whey vary between species, as well as the total protein content. In human milk it is 40% casein and 60% whey. On the other hand, bovine milk is 20% whey and 80% casein. There are numerous proteins that make up these broad classifications and there are substantial interspecies differences in the form and functionality e.g., human casein does not form a true curd and bovine whey has allergenicity issues largely due to alpha-lactalbumin and beta-lactoglobulin. To explain in simple terms casein is acid insoluble (forms the white part of milk) and whey is soluble and was once called milk plasma (and is yellow in color like plasma). Think “Little Miss Muffet”.

Early infant formulas were largely recreations of cow’s milk, with a comprehensive switch to whey dominant formulas (to mimic human milk) not occurring until the 1990’s. Hydrolyzed proteins were used to reduce allergenicity and not the current sports performance dogma of increasing rate of absorption or anabolism. In extreme cases elemental (amino acid only) formulas were necessary although this leads to atrophy of the gut mucosal lining. An early alternative approach to intolerance was the use of soy proteins, which afforded for many infants a nutritional alternative for those with cow’s milk protein allergies and lactose intolerance (or both).

Thus growth and anabolism has its roots in protein blends and alternatives were built around the need to reduce intolerance and allergy, and not to enhance anabolism through rapid absorption. So why does nature use protein blends? The answer is for much the same reasons that the study in question eludes to – to provide a sustained source of amino acids to promote muscle health and development. However, it is more complex than that. Casein, especially bovine casein forms a curd and this limits gastric emptying. As a result there is an increased opportunity for gastric acid to kill microbial contaminants ingested with the milk. This is actually quite important for virtually all four-legged mammals as the udder is underneath the anus, and if anyone has been to a dairy farm then they will appreciate that lactation and defecation are often simultaneous. This is not an issue with the evolutionary trend to a bipedal existence, and as a result the protein form of milk switched from casein dominant to whey dominant. But it remains a blend.

Soy protein has been embroiled in misperceptions largely because of confusion centered on isoflavones that possess estrogenic activities. Soy isoflavones technically are weak partial agonists, so in the context of no background estrogens they can promote a weak estrogenic response, but all partial agonists can act as antagonists in the presence of full agonists. In part because of this receptor-transduction activity, which is a well-appreciated fundamental of drug discovery, soy is associated with a reduced incidence of estrogen-driven cancers (breast, endometrial etc.). Additionally, soy isoflavones have interesting and desirable actions on transcription factors and can restore balance to redox-sensitive transcriptional events that dictate overall muscle growth e.g., by limiting the catabolic effects of inflammation. Inflammation switches off anabolic – repair genes and limiting inflammation maintains their activity. However, soy isoflavones are not proteins, they are polyphenols – they are distinct from soy proteins but present in soy. Soy proteins and peptides have true potential for cardiovascular health. Lowering cholesterol and improving vascular lipid profiles are neglected benefits of soy proteins in the sports performance mindset.

The final aspect that superficially is the most relevant to the Reidy et al. study is the link between timing of protein digestion and plasma levels of amino acids. Proteins which possess different rates of digestion deliver amino acids to muscle tissue for an extended period of time when compared to amino acids, protein hydrolysates or rapidly digested proteins like whey. The advantage here is that the signals and building blocks for anabolism are sustained. A longer lasting signal may be more desirable than a brief, albeit strong burst of amino acids.

From an evolutionary perspective mammalian milk shares this conceptual advantage. The question that is worth revisiting is “Have we in our desire to create simple messages lost our appreciation of the importance of sustained elevations of amino acids to promote muscle growth and repair?” Does a revisit to evolutionary & historical perspectives help us regain this focus and lead to more desirable outcomes?


  1. Reidy P.P. et al. Effect of protein blend vs whey protein ingestion on muscle protein synthesis following resistance exercise.


Dr. Mark J.S. Miller

With the changing demographics of the U.S. population there is growing concern that complications primarily seen in the elderly will become an overwhelming health problem. Cognitive decline, with Alzheimer’s disease (AD) representing an advanced form, represents a substantial societal burden.

An intriguing question is “Can dietary interventions or supplementation affect the cognitive and mental problems associated with aging, by either preventing or delaying the problems?” There have been a series of recent publications to suggest, especially in the early stages, that indeed there are significant benefits to supplementation or dietary intervention.

 The most recent study by Tan et al., 1 addressed the impact of dietary omega-3 fatty acids (the fish oils), particularly those rich in docosahexanoic acid (DHA). DHA levels in red blood cell membranes reflect dietary intake and these levels were compared to brain volume, as measured by MRI, and performance on cognitive tests. It was noted that individuals with the lowest levels of DHA in red blood cell membranes had significantly greater brain atrophy or shrinkage, and they performed significantly worse on tests for logical recall, verbal and visual memory, abstract reasoning, and attention and executive function.

The magnitude of the changes in the study by Tan et al., were dramatic 1. Essentially, those individuals with the lowest quartile of DHA levels had brains that were the equivalent of being two years older in mass and function. These results were independent of other factors that have known influences on brain structure and function e.g., homocysteine levels, physical inactivity and high body mass, and traditional vascular risk factors. In other words, DHA levels in blood was correlated with brain mass and function independently of other risk factors.

This investigation was conducted in middle-aged and elderly subjects free of clinical stroke and dementia, but yet at risk. What is less well appreciated is the effectiveness of omega-3 fatty acids in more advanced forms of the disease.

The conclusion that there is a functional correlation between diet and brain volume and cognition is supported by other studies assessing nutrient profiles. Bowman et al., noted that cognitive performance and brain size were favorable in individuals with high omega-3 fatty acids 2. Whereas high levels of trans fats were associated with compromised mental performance and brain atrophy.

Bowman et al., also noted that individuals with high plasma levels of B vitamins (B1, B2, B6, folate, B12) also displayed larger brain volumes and superior performance on cognitive tests 2. This relationship between B vitamins and mental health has been addressed in specific interventional studies with dietary supplementation with high dose B vitamins for two years (about 10x the current DV) 3, 4. In studies conducted at Oxford University, supplementation with B vitamins suppressed the rate of brain atrophy by a third and like brain volume in conjunction with improved cognitive function 3,4. In the Beyond Ageing Project 5, supplementation with folic acid and vitamin B12 for two years improved cognitive functioning in the elderly. Improved mood and psychological performance has been noted with a high dose B vitamin complex in males between the ages of 30-55 years, suggesting that these benefits are not limited to an aged population 6.

It is also important to note that the dose of B vitamins required for the lowering of homocysteine levels is substantially above the DV, suggesting supplementation is critical. It does appear that the effectiveness of B vitamin supplementation is minimal in subjects where cognitive decline has progressed to the point of diagnosis of Alzheimer’s disease 7,8. This indicates that these nutritional interventions need to be in place as preventative measures and not as a treatment for advanced disease.

Does the same mechanism account for the benefits of omega-3 fatty acids and B vitamins? It appears unlikely although both appear to exert positive outcomes by an action on the vasculature. In the Tan et al. study 1 the benefits were independent of homocysteine levels, whereas B vitamins work by lowering homocysteine levels, converting homocysteine to the amino acids methionine or cysteine. Additionally, the benefits of B vitamins are substantially greater in individuals with high plasma homocysteine levels 2,3. In other words, B vitamins are most effective in subjects with high homocysteine levels and the effectiveness of DHA is independent of homocysteine.

In conclusion, there are intense efforts to develop pharmaceutical interventions to treat dementia and cognitive decline, but unfortunately effective options are not currently available. On the other hand, it appears that maintaining cognitive health for as long as possible can be achieved with simple cost-effective dietary supplementation with omega-3 fatty acids like DHA, and B vitamins.


  1. Tan Z.S. et al., Red blood cell omega-3 fatty acid levels and markers of accelerated brain aging. Neurology 2012; 78: 658-664.
  2. Bowman G.L. et al., Nutrient biomarkers, cognitive function, and MRI measures of brain imaging. Neurology 2012; 78; 241-249.
  3. Smith A.D. et al., Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS One 2010; 5; e12244
  4. De Jager C.A. et al., Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial. Int J Geriatr Psychology 2011; DOI: 10.1002/gps.2758
  5. Walker J.G., et al., Oral folic acid and vitamin B-12 supplementation to prevent cognitive decline in community-dwelling older adults with depressive symptoms – Beyond Agein Project: a randomized control. Am J Clin Nutr 2012: 95; 194-203.
  6. Kennedy D.O., et al., Effects of high-dose vitamin complex with vitamin C and minerals on subjective mood and performance in healthy males. Psychopharmacology (Berl) 2012: 211; 55-68.
  7. Aisen P.S. et al., High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial. JAMA 2008: 300; 1774-1783.
  8. Van Dyck C.H. et al., Cognitive and psychiatric effects of vitamin B12 replacement in dementia with low serum B12 levels: a nursing home study. Int Psychogeriatr 2009: 21; 138-147.


By: Mark J.S. Miller, PhD, MBA, FACN, CNS

The genome is extraordinarily stable. Changes in the code are rare, albeit dramatic when noted, but changes only evolve over millennia. How else can we share so much of our code with evolutionary relatives: lab mice and primates?

So the genetic code must be very stable. So does that mean if your genetic lot determined that youwill be fat or slow or whatever body characteristic you do not enjoy, then that is your lot in life? It cannot be altered?

That is the consensus that pervades our thinking, but in the last few years there is a revolution in our knowledge of genes and how they affect our form and function. That revolution is the science of epigenetics. This revolution will totally redefine our understanding of health and disease. It is a game changer.

But what is epigenetics? The word epi is from the Greek meaning “above” or “on top of”, and refers to chemical tags that sit directly on the DNA or proteins that wrap up DNA. These tags do not change the code but they determine how the code is used. In computer terms, the DNA code (or genome) is your hardware, and the epigenome is the software. Each cell has the same hardware, but the diversity of form and function is controlled by the epigenome or genetic software. Imagine the chaos if a cell lost its identity and started changing its software – a skin cell acting like a neuron, or developing teeth in your liver, or hair in your cartilage? The attractive thing about the epigenome is that we can measure it, these tags can be tracked and changes noted.

So while the epigenome also needs to be stable, it can adapt and change as the environment dictates. That may be due to exposure to chemicals or nutritional factors. However, as it relates to body composition, there was a recent publication that truly shakes our thinking of how our genes respond to environmental influences, which is at the core of our survivability.

Barres et al., 1, studied the effects of acute exercise on our genetic software, our epigenome, the chemical tags that determine which gene is activated and which ones are dormant. One would think that acute exercise would do nothing as the code is too stable, but significant changes were evident. In particular three genes were affected.

  • PGC-1a, which protects against sarcopenia or muscle loss/wasting, bone loss and is anti-inflammatory
  • PDK4, which regulates the entry of carbohydrates into mitochondria for energy production
  • PPAR-d, which promotes Type 1 muscle fiber development, these fibers are associated with endurance and obesity resistance

Studies were performed in humans and then verified in isolated mouse muscles and showed that acute exercise reduced numbers of methyl groups (small one carbon tags) through out the genome, but particularly these 3 genes, and this resulted in increased expression or activity of these genes.

What we can take from this is that exercise fundamentally alters how we use our genetic resources within skeletal muscle.  Exercise, even acute, changes the processes that regulate how we use fuel, the type of muscle fibers and promotes a body composition type that is lean. These events are independent of classic drivers of caloric intake-expenditure equations, but rather mediated through a change in our genetic software, our epigenome. 


  1. Barres R et al. Acute exercie remodels promoter methylation in human skeletal muscle. Cell Metabolism 2012: 15; 405-411.

By: AdvoCare Scientific & Medical Advisory Board Members Dr. Leanne M. Redman & Dr. Sid Stohs

Fructose, the most common sugar found in fruits, vegetables and other foods, has received a bad rap recently for its association with close relative, high fructose corn syrup (HFCS). Many studies have related high fructose corn syrup with the obesity epidemic in the US as its increasing amount in our diet has been linked to the rise in obesity in adults and children.

HFCS is derived from cornstarch and is a mixture of fructose and glucose. The amount of fructose in HFCS varies from 42 – 55%, the remaining sugar being glucose. Therefore, HFCS has the approximate composition of glucose and fructose that occurs in table sugar (sucrose) which are present in a 50:50 ratio.  HFCS is the major sweetener in our diet and is also a major source of added calories. HFCS is used extensively to sweeten soft drinks, fruit drinks, sports drinks, teas and other processed drinks. It is also used in baked goods, jams, yogurts and other sweetened foods. HFCS is used because of its availability as a liquid and the ability to readily blend with food and beverage constituents.

A recent paper has been published in the Annuals of Internal Medicine dispelling the myth that fructose in our diet contributes disproportionately to weight gain. In this paper, the results of 31 studies in 637 individuals were combined to determine the role of fructose in the diet on body weight changes.  People in these studies ate diets that were matched for the number of calories but that differed in the amount of fructose. This important paper shows that when the calorie levels of the different diets were identical, there was no preferential effect for fructose to produce weight gain. A careful look at only those studies reporting weight gain with fructose intake identified that these diets while different in the amount of fructose, were not matched for calories. Weight gain occurred with diets that provided more calories, which makes sense. Fructose could not be solely blamed for the weight gain, because the fructose diets provided more calories.

In summary, fructose is a type of sugar that is found widely in fruits and vegetables as well as in HFCS. The Dietary Guidelines for Americans 2010 suggests that sugar, especially refined sugars should be consumed in moderation. Fructose, like all sugars can become a problem for weight gain when it is eaten in excess. So the mere presence of fructose, say as HFCS, does not dictate a health problem or weight gain, but like other sources of calories if it is consumed in excess then issues may arise. Specifically, the consumption of a diet high in fructose promotes the development of three of the clinical features associated with metabolic syndrome, namely, hyperlipidemia (excess fat in the blood), visceral adiposity (abdominal fat) and insulin resistance.

By Dr. Leanne M. Redman, Ph.D.

With the holiday season recently behind us many are embarking on New Year’s resolutions to shed those extra holiday pounds. While healthy eating may be part of our daily lives for 335 days of the year, everything we know and live by seems to fall by the wayside around the holidays. Most of us will overindulge in the traditional calorie-rich holiday foods that are customary to our culture. The question is, should we pay attention to where the extra 500-1,000 calories we are eating is coming from?

A collection of studies done over a 50 year period suggested that less weight is gained when individuals overeat a diet that contains either a low amount of protein (less than 5% of the total calories eaten) or a high amount of protein (more than 20% of the total calories eaten). This observation was recently tested in a randomized controlled trial at Pennington Biomedical Research Center in Baton Rouge, Louisiana. Twenty-five young men and women overfed about 900 calories a day for 8 weeks. The participants ate 1 of 3 diets where the total calories from protein diets were either 5% (low amount), 15% (normal amount) or 25% (high amount). In this state-of-the-art study, participants lived at the Research Center for about 10 weeks so the changes in body weight, body fat and metabolic rate could be closely monitored and participants would be forced to refrain from exercising to burn off the excess calories.

Inline with the previous research, after the 8 week study individuals overeating the diet low in protein gained about 50% less weight (7 lb or 3.16 kg) compared to those eating the diet containing normal (13.3 lb or 6.05 kg) or high (13.5 lb or 6.17 kg) amount of protein.  The most interesting discovery was in how this body weight was gained. Using a unique kind of X-ray to measure body fat and muscle, or lean body mass, the researchers found that despite the differences in weight gain, all 3 diets caused participants to gain the same amount of body fat (7.1 lbs or 3.2 kg).  The discrepancy between weight gain then was due to the difference in the amount of body protein (or muscle) that was made.

This landmark study points out that people need to understand that the number on the scale does not necessarily provide all the information with regard to their health. Calories alone are important in controlling fat gain when overeating. Because body fat is the hallmark feature of obesity and a major risk factor for increasing health problems such as type 2 diabetes and heart disease, obesity treatments should focus on reducing fatness rather than body weight per se.

By Dr. Robert Hackman

The level of cholesterol in your blood is important, and keeping that level in a healthy range is part of a wellness lifestyle. High blood cholesterol, particularly when packaged as LDL cholesterol, can damage the smooth lining of your blood vessels, increase fatty plaque formation that clogs arteries, and increase one’s risk of a heart attack, a stroke or other cardiovascular crisis.

But cholesterol in food is not the same as cholesterol that clogs arteries. For most people, the amount of cholesterol eaten has a relatively minor impact on the amount of cholesterol circulating in the blood (1). Most of us make far more cholesterol in our bodies (specifically in our liver) than we get from the food we eat, and most of us trigger our liver to pump out cholesterol by eating saturated (animal) fats and trans fats, rather than from eating cholesterol-rich foods.

Egg consumption is a good example of how our understanding about nutrition and heart health has progressed. An egg contains roughly 200 mg of cholesterol (which is found in the egg yolk), and eating eggs was thought a few decades ago to be a major factor raising blood cholesterol levels. However, after 40 years of studies, we still don’t have any good evidence that eating eggs raises cholesterol levels in most people or is a contributing factor to heart disease. 

Moderation is still important when it comes to dietary cholesterol intake. A recent study reported that eating an egg per day (up to 7 in a week) was generally safe for most people, but egg intake beyond this level was still considered a risk factor for heart failure (2).

While most people do not show much change in blood cholesterol levels after eating cholesterol-rich foods, about 30% of the population does respond. Especially for people who have difficulty controlling their blood cholesterol levels, or who have heart disease already, it is important to pay close attention to food choices and limit eating cholesterol-rich foods to no more than the equivalent of three egg yolks per week. A recent study reported that higher intakes of eggs and other sources of dietary cholesterol were associated with increased risk of cardiovascular disease and death among older adults with type 2 diabetes (3), so moderation would be important for this group as well.

Practicing a healthy lifestyle, which includes wise food choices, consuming scientifically-based nutrition supplements, regular exercise and a good night’s sleep, is the best way to feel better, look better and perform better – When it comes to eggs, focus on the total meal, rather than just one food. While eggs are a good source of protein, and don’t affect blood cholesterol levels for most people, adding cheese, fried potatoes, or bacon or sausage can boost the intake of saturated fats and trigger a rise in blood cholesterol for most of us.

  1. Fernandez ML.  Dietary cholesterol provided by eggs and plasma lipoproteins in healthy populations. Curr Opin Clin Nutr Metab Care 9:8-12, 2006.
  2. 2.   Djousse L, Gaziano JM.  Egg consumption and risk of heart failure in the Physicians’ Health Study.  Circulation 117:512-6, 2008.
  3. Houston DK, Ding J, Lee JS. Dietary fat and cholesterol and risk of cardiovascular disease in older adults: the Health ABC Study.  Nutr Metab Cardiovasc Dis 21: 430-7, 2011.

AdvoCare Scientific & Medical Advisory Board member Dr. William Kraemer recently published an article on the benefits of nutritional supplements and how they can help reduce inflammation and improve recovery, featuring BioCharge.

Read the article in Nutrition Journal.


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