Integrated Supplements Blog

A Case Against Arginine Supplementation

The conditionally essential amino acid arginine is involved in a wide variety of biological functions. It’s needed for proper immune function, tissue–building, and for the production of a wide array of biological substances. Arginine can be found in almost every protein–containing food, and is plentiful in most modern diets.

But research has indicated that high (multi–gram) doses of supplemental arginine may be harmful if taken over extended periods of time.

How could this valuable, seemingly harmless nutrient (or even, seemingly beneficial nutrient, if you listen to the supplement industry) cause harm?

The answer lies within the wise words of Paracelsus, in which we find a fundamental tenet of nutrition itself:

“...only the dose permits something not to be poisonous."

First, A Little Background…

During the mid 20th Century, as the nutritional shortcomings of the increasingly industrialized American food supply became more widely recognized, nutritional supplements and the concept of “health food” were born.

At this time, the goal of “health foods” and vitamin supplements was generally to “fill the gaps” and replace nutrients which had become lacking in our uniquely–modern diet.

But, as nutritional science advanced during the latter part of the previous century, nutritional supplements began to shed their original role as mere “nutritional insurance,” and took on the role of sometimes significant therapeutic agents.

The effects of high–doses of isolated nutrients began to be investigated more closely, and before long, some physicians and researchers were claiming remarkable successes, not merely in correcting nutrient deficiencies, but in rectifying some full–blown disease states. Many of these pioneering researchers began advocating supraphysiologically high dosages of isolated nutrients and nutrient mixtures as alternatives to drug treatment for medical disorders such as schizophrenia, heart disease, and cancer.

These “megadoses” of nutrients became the hallmark of what is known as orthomolecular therapy, a practice whose advocates famously included chemist, and two–time Nobel Laureate, Linus Pauling.

Around this time is when the line first began to blur between the “nutrients–as–nutrients” paradigm, and the “nutrients–as–drugs” paradigm we increasingly see today. Where the orthomolecularists were often ridiculed in their early days, today, even mainstream medicine has at least begun to respect the possibility that some nutrients can, indeed, be effective pharmacological agents.

Dose is Everything

But while the orthomolecularists were medical professionals who used high–doses of nutrients to treat disease, the logical progression of their ideas gave way to the concept of life–extension nutrition. By the early 1980’s the idea of manipulating ones’ diet via unprecedented types of supplementation was being advocated as a way to prevent (or dramatically slow) the aging process itself. As a result, millions of Americans, armed with little to no biochemical knowledge, began to delve in the emerging field of anti-aging supplementation which continues today.

Of course, large numbers of people taking a pro–active stance towards their health is, generally, a very good thing. But it’s important to state the following fact explicitly: Although a case could be made that high doses of nutrients represent a relative degree of safety when compared to some pharmaceutical drugs, it’s important to realize that high–doses of isolated nutrients, more often than not, are imparting drug–like, not nutritive, effects. As such, the fact that a substance is a nutrient, or that it’s “found in food” does not, in and of itself, give us reason to believe that a substance is safe when consumed in high amounts in isolated form.

Enter Arginine

One of the hallmarks of these early life–extension–oriented nutritional programs was the supplementation of high doses of the amino acid, arginine. Based upon what we now know was a shockingly narrow view of the complexities of arginine metabolism, multi–gram doses of arginine were recommended in order to stimulate the release of the youth-associated growth hormone from the pituitary gland.

And several years later, in the early 1990’s, a groundbreaking book on sports nutrition written by an eminent PhD and sports nutrition expert also advised athletes to consume multi–gram doses of arginine in order to, similarly, increase growth hormone levels.

Generally speaking, growth hormone had (and often still has) an almost mystical allure among the anti–aging and athletic crowd as some sort of endogenously–produced fountain of youth, destined to improve performance and reverse the hands of time.

But, despite the initial enthusiasm, stimulating growth hormone release via arginine (or any other nutritional substance, for that matter) simply doesn’t seem to offer the anti–aging or performance–enhancing results which were once promised.

Although arginine may very well increase growth hormone, some studies show that arginine supplementation dramatically reduces athletic performance. The following study, for example, found that arginine supplementation was associated with average marathon times 23 minutes longer than predicted:

Study Link – The effect of arginine or glycine supplementation on gastrointestinal function, muscle injury, serum amino acid concentrations and performance during a marathon run.

Quote from the above study:

Finish times were longer than predicted (23+/–21 min[utes]… for the [Arginine] group.

Arginine and Nitric Oxide

By the mid 1990’s, the arginine–for–growth–hormone fad had pretty much run its course, only to have arginine revived a decade later, this time as a “nitric oxide booster.”

But, in several editions of the Integrated Supplements Newsletter, we explained the big picture behind nitric oxide, and showed many reasons why people may want to think twice before consuming large amounts of nitric oxide precursors like arginine.

Nitric Oxide The Big Picture – Part 1

Nitric Oxide The Big Picture – Part 2

Nitric Oxide The Big Picture – Part 3

Arginine – Reason for Concern

Knowing that one of the functions of nitric oxide is to dilate blood vessels, it wasn’t all that long ago that some within the medical community had high hopes for the nitric oxide precursor, arginine, as a treatment for heart disease - but the fact that arginine repeatedly caused harm in many of the studies in which it was tested has given researchers reason for concern.

It turns out that, in controlled studies, patients taking arginine often fared notably worse than those not taking the amino acid. One important trial in heart–disease patients even had to be stopped prematurely because of an increase in death in the group taking arginine supplements:

Study Link – L–Arginine Therapy in Acute Myocardial Infarction The Vascular Interaction With Age in Myocardial Infarction (VINTAGE MI) Randomized Clinical Trial.

Quote from the above study:

6 participants (8.6%) in the L–arginine group died during the 6–month study period vs none in the placebo group (P = .01). Because of the safety concerns, the data and safety monitoring committee closed enrollment. . . L–Arginine, when added to standard postinfarction therapies, does not improve vascular stiffness measurements or ejection fraction and may be associated with higher postinfarction mortality. L–Arginine should not be recommended following acute myocardial infarction.

Study Link – L–Arginine Supplementation in Peripheral Arterial Disease – No Benefit and Possible Harm.

Quote form the above study:

Although absolute claudication distance improved in both L–arginine– and placebo–treated patients, the improvement in the L–arginine–treated group was significantly less than that in the placebo group (28.3% versus 11.5%; P=0.024). . . As opposed to its short–term administration, long–term administration of L–arginine is not useful in patients with intermittent claudication and PAD.

Study Link - Adverse Effects of Supplemental L–Arginine in Atherosclerosis

Contrary to what was first assumed, there are several mechanisms by which arginine supplementation can cause harm – the most likely being that supplemental arginine is very likely to convert largely to the potent cellular toxins, superoxide and peroxynitrite (we discussed this effect extensively in the above–linked newsletters on nitric oxide).

But recent research sheds light on a related mechanism responsible for the toxicity of high–dose arginine – its ability to interfere with creatine kinase activity. Creatine kinase is the cellular enzyme responsible for allowing creatine to rapidly regenerate the energy molecule, ATP. Interfering with this enzyme system is known to produce varied toxic effects (in our previous blog post, we saw how the chemical (and, unfortunately, dietary supplement ingredient), guanidinopropionic acid, exerts its cardiovascular toxicity by a similar mechanism).

The following study showed arginine to interfere with creatine kinase activity in the cerebellum of rats:

Study Link – Arginine administration reduces creatine kinase activity in rat cerebellum.

Quote from the above study:

The data indicate that the reduction of CK [creatine kinase] activity in cerebellum of rats caused by arginine was probably mediated by NO and/or its derivatives ONOO(–) [superoxide] and other free radicals. Considering the importance of CK for the maintenance of energy homeostasis in the brain, if this enzyme inhibition also occurs in hyperargininemic patients, it is possible that CK inhibition may be one of the mechanisms by which arginine is neurotoxic in hyperargininemia.

The fact that arginine has caused many negative effects when administered in multi–gram doses has surprised even some very intelligent medical researchers. But although the research clearly gives any rational person reason to think twice before engaging in arginine supplementation, arginine–containing products continue to be sold with almost no mention whatsoever of their potential risks.

So, as the line continually blurs between nutrients and drugs, and as inadvertent “self–medication” becomes more and more common, the take–home lesson is clear:

Any person looking to enhance his or her health through supplementation should take heed of the relevant research – and should not simply assume that a nutrient is safe at high doses merely because the same nutrient happens to be “found in food.”

This sort of false sense of security is often perpetuated by the supplement industry, itself, but may sometimes be putting our health in serious danger.

We’ll have more research coming your way soon – stay tuned.

Guanidinopropionic Acid - What’s in Your Creatine Product?

In our newly–released audio program, The Truth About Creatine, we examine the extensive scientific research documenting the safety and effectiveness of pure creatine monohydrate. Given its stigma as a mere bodybuilding supplement, people are often surprised to learn just how well–researched creatine is, and how much promise this simple nutrient has shown, not only for improving athletic performance, but also in helping to combat some of the major health maladies of our time.

But despite the existing research, some companies within the sports supplement industry have taken to formulating creatine–containing products with untested and potentially harmful ingredients.

Take, for example, the now–common dietary supplement ingredient called guanidinopropionic acid (GPA) which can be found in many pre–workout drinks and “nitric oxide boosters.” Ironically, GPA is known as a creatine antagonist, which means that it blocks the cellular uptake of creatine. As a research chemical, GPA is commonly administered to cause the depletion of creatine from cells.

Creatine supports cellular energy production in all cells including cells of the musculature, brain, nervous system, and heart. As such, creatine is remarkably protective of cellular health, and any substance which depletes it can only honestly be described as a toxin. For this reason, GPA has simply not been tested in humans. This fact is reason enough to avoid ingesting it, but animal studies in which GPA has been administered give us every reason to believe that GPA may be overtly harmful.

In our audio program on creatine, we referenced a 2001 study published in the journal, Circulation, in which GPA was fed to laboratory animals. To examine the possible protective role of creatine during and after a heart attack, the researchers used a procedure called coronary ligation to block blood flow to the heart of the test animals. Under normal conditions, coronary ligation is fatal to 40 to 50 percent of animals, but in this study, coronary ligation was fatal to a full 100% of the test animal consuming GPA. By depleting creatine, GPA prevented the heart from producing the emergency energy it needed to survive.

Study Link – Chronic Phosphocreatine Depletion by the Creatine Analogue ß–Guanidinopropionate Is Associated With Increased Mortality and Loss of ATP in Rats After Myocardial Infarction.

Quote from the above study:

Rats with an 87% predepletion of myocardial PCr [phosphocreatine] content cannot survive an acute MI. Chronically infarcted hearts subjected to additional PCr depletion cannot maintain ATP homeostasis…

The most remarkable finding of the present study is that when hearts were prefed with GP[A] for 2 (n=43) or 4 (n=45) weeks, leading to a 65% and 74% reduction of PCr content, respectively, the 24–hour mortality of prefed rats undergoing coronary ligation was 100% (P<0.0001, 2=27.69, MI+GP versus prefed MI), whereas in untreated rats, mortality for this procedure is 40% to 50%. This finding clearly shows that rat hearts with a 65% depletion of PCr and a 75% reduction of Flux CK are unable to cope with the stress of an acute MI, or, in other words, that an intact PCr–CK [Creatine Kinase] system is needed to survive an acute coronary ligation.

Because GPA, in essence, robs the cells of creatine, GPA can alter the substrates which cells use to produce energy. As a defensive mechanism when GPA depletes creatine stores, cells can use more glucose or fatty acids as fuel instead of relying on creatine. For this reason, companies trying to sell you GPA–containing products will tell you that GPA can “burn fat,” or “lower blood sugar,” but they are unlikely to tell you about the above research showing GPA to induce pathological changes in the heart, or of similar research showing GPA to cause pathological changes to the brain, and muscles.

Of course, when confronted with the fact that substances like GPA have the potential to do serious harm, some people contend that the doses of these ingredients found in nutritional supplements are too low to do any meaningful damage. This says nothing however, of the long–term harm which could be done by consuming these ingredients even in low doses, nor does it address the important fact that none of these ingredients have even been shown to be effective for their stated purpose.

Let’s not forget, that if a company puts an ingredient in their product, it’s incumbent upon them to provide research to show that the doses they are recommending are both safe and effective. But companies using GPA, and a whole host of other ingredients found in some creatine–containing products simply cannot show that these ingredients are either safe or effective

Far too often in the sports supplement industry, products are formulated with new and untested ingredients simply so the company selling them can create the image of being on the “cutting edge” of product development. Time and time again however, using unproven ingredients simply makes these companies look foolish and irresponsible in the eyes of anyone who has actually studied the existing research.

We’ll have more of this research coming your way soon – stay tuned.

Related Articles:

Study Finds Creatine Improves Health and Increases Lifespan in Mice

Nitric Oxide – The Big Picture Part 1

Creatine Q&A Fact vs. Fiction – Part 3

FDA Issues Warning Regarding Popular Weight-Loss Supplement

May 1, 2009 – The U.S. Food and Drug Administration today issued a consumer warning regarding the use of one of the most popular diet and weight–loss supplements sold in the United States. The product has been associated with numerous incidences of liver injury and one death:

FDA Warns Consumers to Stop Using Hydroxycut Products
Dietary Supplements Linked to One Death; Pose Risk of Liver Injury

Quote from the FDA release:

The FDA has received 23 reports of serious health problems ranging from jaundice and elevated liver enzymes, an indicator of potential liver injury, to liver damage requiring liver transplant. One death due to liver failure has been reported to the FDA. Other health problems reported include seizures; cardiovascular disorders; and rhabdomyolysis, a type of muscle damage that can lead to other serious health problems such as kidney failure.

The product manufacturer/marketer is in the process of issuing a recall for this, and many similar products sold under the same brand name. 

The scientific literature also contains case reports of liver toxicity associated with the use of the above-mentioned dietary supplement:

Link – Two Patients with Acute Liver Injury Associated with Use of the Herbal Weight–Loss Supplement Hydroxycut

(Report begins on page 477 of the document)

 Quotes from the above report:

Patient 1, a 27–year–old man, presented with 8 days of fatigue and jaundice. He had been taking Hydroxycut for 5 weeks, 3 tablets 3 times per day.

Patient 2, a 30–year–old man, presented with 10 days of jaundice, fever, vomiting, and fatigue. For 5 days, between the 16th and 11th days before presentation, he had been taking 9 tablets of Hydroxycut per day.

In the April 2009 edition of the Integrated Supplements Newsletter, we discussed the danger of liver toxicity associated with the use of potent herbal extracts currently being included in dietary supplements – including the above–mentioned product. Isoflavones from soy, polyphenols from green tea, and many other plant chemicals currently being promoted as “antioxidants,” are often found in highly concentrated amounts in dietary supplements. Broadly, these chemicals can be classified as phytoestrogens, or, plant chemicals which are similar to estrogen in structure and in many biological functions.

As hormonally active chemicals, these herbal extracts often place a far more significant burden on the liver than many people realize. The liver is called upon to detoxify food–based and herbal hormones such as these, and the doses often found in supplements appear to sometimes damage liver function significantly.

As a company dedicated to producing only safe and effective dietary supplements, we at Integrated Supplements have gone on record warning against the use of many common products sold as dietary supplements, including potent phytoestrogenic herbal extracts.

We’ve also warned against the use of other common supplement staples such as:

• Whey Protein Concentrate

• Soy Protein

• Caseinate Powders

• Nitric Oxide “Boosters”

• Concentrated Fish Oils (in the doses often recommended)

• Flaxseeds and Flax Oil

Although the diet product mentioned above is one of the most recognizable products in the nutritional supplement industry, its formula is not unique. Scores of similar products line the shelves at supplement stores, drugstores, and supermarkets throughout the country. As supplement use becomes more mainstream, the number of adverse events related to dietary supplement usage is sure to increase, unless we find a way to create educated and impassioned dietary supplement consumers.

Those of us who value our access to dietary supplements will be well served to take the above warning seriously. In the United States, we currently have the freedom to choose a nearly countless array of nutritional substances. But a corollary of the freedom to choose is the responsibility of educating ourselves – and of honestly assessing the risks involved in consuming any given product.

We implore supplement users, retailers, medical professionals, and public health authorities to examine the research–backed articles on our website, www.IntegratedSupplements.com. As a result of shoddy manufacturing practices, inferior raw material selection, and overall biological ignorance with regard to product formulation, many nutritional supplements now possess a greater risk profile than ever before. Similarly, with the advent of increasingly potent herbal extracts (many of which are often combined haphazardly in single formulations), supplement use has strayed ever–so–slowly away from its roots in nutrition, and towards the realm of wanton and inadvertent self–medication.

In the midst of a nutritional landscape marred by short–range thinking, dietary supplements should rightfully offer us the ability to compensate for an increasingly nutritionally–degraded food supply. But far too often, in actual practice, dietary supplements merely serve to create more health problems than they solve.

This is a trend we at Integrated Supplements are intent on combating head–on.

We’ll have more research coming your way soon.

Study Shows Creatine Supplementation May Prevent Aging and Degeneration

The dietary supplement, creatine, has risen to prominence in recent decades largely because of its effectiveness in helping to increase muscular size and strength. But, while creatine is still widely though of as a mere “sports supplement,” this remarkable substance is slowly beginning to gain the respect it deserves as a remarkable anti–aging nutrient as well.

On a cellular level, high creatine stores allow for the rapid recycling of the universal energy molecule, adenosine triphosphate, or, ATP. More specifically, supplemental creatine is able to increase stores of a chemical called creatine phosphate, which donates phosphate and “recharges” ATP (which means that ATP doesn’t have to be produced again “from scratch”). But, while the mechanism by which creatine works may be simple, the repercussions of this single chemical reaction are nothing short of profound for our health and longevity.

Energy is Life

When it comes to maintaining the vitality of youth, all of us are only as good as the efficiency of energy production, or in other words, the functioning of our mitochondria. In fact, keeping these energy–producing cellular structures intact and free from harm (or, finding ways of replacing them if they do become damaged) is increasingly being seen as a fundamental goal of anti–aging science.

To make a long biochemical story short, the mitochondria in our cells are unique among cellular structures in that they contain their own DNA (as you may remember from high school biology class, the vast majority of what we consider “our” DNA is found in the nucleus of the cell). Mitochondrial DNA (mtDNA), though relatively simple relative to the complex nuclear DNA, is still remarkably important as it contains the blueprints which encode for the building of the energy “assembly line” known as the respiratory chain.

Note: The fact that “our” DNA in the nucleus of the cell, and the mitochondrial DNA appear to be of different evolutionary origin has led many scientists to believe that human mitochondria were once bacteria which have adapted over eons to become a normal part of our physiology.

Because it resides on the “front lines” of energy production within the mitochondria, mtDNA is quite susceptible to damage via reactive oxygen species (ROS) which are natural byproducts of energy metabolism. This means that, unlike the DNA which is protected within the cellular nucleus, mitochondrial DNA is relatively easily damaged, and nearly impossible to repair.

Scientists have begun to gather evidence that damage to mitochondrial DNA is likely to play a fundamental role in such things as neurodegeneration, skin aging (a.k.a. photoaging), muscle loss and cancer:

Study Link – Analysis of potential cancer biomarkers in mitochondrial DNA.

Study Link – Mitochondrial DNA mutations in human cancer.

Study Link – Accumulation of mitochondrial DNA deletion mutations in aged muscle fibers: evidence for a causal role in muscle fiber loss.

Study Link – Mitochondrial DNA mutations in disease, aging, and neurodegeneration.

So, even a brief look at the research makes it very clear that anti–aging science is in dire need of substances which can protect the mitochondria (and its DNA) from the relentless assault of reactive oxygen species.

Creatine Prevents Damage To Mitochondrial DNA

A recent study published in the Journal of Investigative Dermatology shows that creatine may be just such a substance:

Study Link – Creatine supplementation normalizes mutagenesis of mitochondrial DNA as well as functional consequences.

The researches who conducted the above study tested the effects of in vitro creatine supplementation in ultraviolet A–treated fibroblast cells.

Ultraviolet A (UVA) is known to be the spectrum of ultraviolet light largely responsible for skin aging [and, although ultraviolet B (UVB) is commonly implicated, some research suggests a significant role for UVA in the development of skin cancers as well]. The researchers attempted to test the effects of creatine against physiologically–relevant levels of UVA as could be obtained from sunlight “during a regular summer holiday.”

Although such exposure to UVA was sufficient to cause functionally–relevant mtDNA mutations, these mutations were prevented in the presence of creatine.

The researchers reported:

Our data suggest that mtDNA mutations induced by sublethal repetitive UV–exposure of a magnitude acquirable during a regular summer holiday suffices to result in functionally relevant changes and that creatine supplementation of cells is able to normalize mtDNA mutagenesis and functional impairment.

Interestingly, the researchers noted that in this case, creatine didn’t confer its protective effect upon the mitochondria via scavenging ROS directly. That is to say that creatine didn’t exhibit a direct antioxidant effect per se. Rather, as the researchers hypothesized, the rapid recycling of ATP caused by the presence of creatine may have taken a metabolic “burden” off of the mitochondria.

In not having to produce ATP de novo (“from scratch,” so to speak), the mitochondria therefore don’t have to run the entire “assembly line” of energy production. The result is likely to be less reactive oxygen species generated from de novo ATP synthesis, and less overall free radical damage to the mitochondria.

Such cell–protective effects of creatine have already led to investigations of the nutrient’s role in muscular, cardiovascular, and neurological health; and if creatine can reduce cell damage caused by ultraviolet radiation as was shown in the above study, it appears we can add dermatological health to this list as well (it’s easy to imagine that we may see creatine–based skin care products hit the market before long).

Again, the take home message is clear: Creatine is far more than just a bodybuilding supplement. Creatine improves the efficiency of energy production at a fundamental level, and offers cellular protection to a wide range cells throughout the body. The implications of this may very well be a slowing of the aging process and an extension of lifespan for those who maximize their creatine levels.

Only time will tell.

Related Articles:

Study Finds Creatine Improves Health and Increases Lifespan in Mice

Study Finds Creatine Improves Health and Increases Lifespan in Mice

Recently, in the Integrated Supplements Blog, we’ve commented on how valuable lifespan studies can be for those of us looking to make truly healthy lifestyle choices. Lifespan studies examine the effects of certain interventions over the entire lifespan of the test animal – which gives a far more accurate indication of long–term effectiveness and safety rather than simply looking at biological markers in the short–term.

We’ve seen previously, how substances which support the production of beneficial intestinal bacteria (like certain soluble fibers), or substances which reduce the toxic burden of “bad” intestinal bacteria (like activated charcoal), have both been associated with an increase in lifespan:

Can Some Types of Dietary Fiber Extend Your Life?

Now, it seems that we can add another entry to the list of dietary/supplemental substances which may be able to increase healthy lifespan. Surprisingly to many, this substance is creatine monohydrate.

Researchers from Germany recently tested the effects of creatine given to one year old female mice. The average lifespan of the mice given creatine increased by 9%, and the creatine–supplemented mice also exhibited inproved performance in neurobehavioral/learning tests. Researchers also found a trend toward a reduced level of reactive oxygen species as well as a significant reduction in the fatty age–pigment, lipofuscin (lipofuscin can be noticed on the skin in the form of unsightly “age spots” or “liver spots,” but its presence in all tissues, including the brain, is a clear marker of the degeneration of aging).

Study Link – Creatine improves health and survival of mice.

Quote from the above study:

The median healthy life span of Cr–fed mice was 9% higher than in control mice, and they performed significantly better in neurobehavioral tests. In brains of Cr–treated mice, there was a trend towards a reduction of reactive oxygen species and significantly lower accumulation of the "aging pigment" lipofuscin. Expression profiling showed an upregulation of genes implicated in neuronal growth, neuroprotection, and learning. These data show that Cr improves health and longevity in mice. Cr may be a promising food supplement to promote healthy human aging.

Creatine – Not Just For Muscles

Long–known as an aid to muscle building and strength gains, creatine has also been investigated for the benefits it may offer in regards to nerological and overall health. The researchers who conducted the above study were prompted to do so by the promising outcomes achieved when creatine was studied in relation to the brain–disorders, Parkinson’s and Huntington’s disease. It is now certain that creatine plays an integral role in the rapid recycling of cellular energy (in the form of ATP), not only in our muscles, but in various tissues of the body, including the brain and neurological system.

As we’ve covered in the Integrated Supplements Newsletters on oxidative stress, the more efficiently our cells produce energy, the fewer harmful free radicals will be produced. On a fundamental level, any viable anti–aging strategy must involve the means to reduce the cumulative burden of oxidative stress – and creatine appears to do just that.

Because creatine is involved in a process which allows the cells to rapidly and efficiently produce energy - without engaging the full cellular machinery involved in producing energy from carbohydrates or fats, creatine is likely to be a major weapon in the fight against oxidative stress and aging.

This study, and others, make it clear that creatine supplementation is likely to have “brain–building” as well as muscle–building effects – not only to delay aging, but even to boost mental function and intelligence as well.

At Integrated Supplements, we’ll have more of the amazing “outside–the–box” creatine research coming your way soon – stay tuned.

Related Articles:

Rancid Fats and Oxidative Stress - Strategies To Reverse Aging - Part 1

Combating Oxidative Stress - Strategies to Reverse Aging - Part 2

Studies Show Potential Dangers of Denatured Protein in Foods and Protein Supplements

As a reader of the Integrated Supplements Blog, you now know full–well that all protein supplements are not created equal.

You know that the cholesterol found in whey protein concentrate is prone to oxidation; and that oxidized cholesterol is a major driving force behind the development of arterial plaque of heart disease:

Oxidized LDL – The New "Bad" Cholesterol

Study Finds Oxidized Cholesterol In All Dairy Powders Tested – Levels Increased With Storage

Oxidized Cholesterol in Dairy Protein Powders Part 2

How To Combat The REAL Risk Factor For Heart Disease And Aging

You know that only properly prepared whey protein isolate will deliver the full antioxidant and immune system–supporting functions which whey protein is known for:

Are You Wasting Your Money On Whey Protein? Studies Find Up To 53% Denatured Protein in Whey Protein Concentrate.

If Your Protein Supplement Doesn’t Boost Glutathione, You’re Just Wasting Your Money

And, thanks to several recent blog posts:

Protein–Derived Toxins in Foods and Nutritional Supplements

Neutralizing Protein–Derived Toxins With Soluble Fiber and Resistant Starch

You know that the denatured proteins found in many protein powders, bars and ready–to–drink protein shakes are far from healthy, and are instead likely to impart many harmful effects with continued use.

At Integrated Supplements, we’ve touted the importance of undenatured protein supplements from day one; but as a seemingly lone voice of reason in an industry increasingly being taken over by short–sighted greed and baseless promotion, we’ve watched as other supplement companies continue to churn out low–quality, and potentially harmful nutritional products – while shamelessly masquerading them as the latest in cutting–edge nutrition.

So, as companies within the food and nutritional supplement industry continue to ignore the fact that their products contain a wide array of protein–based toxins, we think it’s time to set the record straight. We think it’s important to show our customers what the scientific research really has to say about the denatured and altered proteins found in many protein–containing nutritional products.

Protein Denaturation – A Matter of Degree

In simple terms, a protein is said to be denatured when its chemical shape changes in response to heat or extremes of pH (acid or alkaline). Some proteins (many enzymes, for example) lose their biological function when denatured; and, as we’ve seen elsewhere, particularly fragile proteins from whey protein isolate (The ones which aid in glutathione synthesis) must remain undenatured in order to exert their full biological activity.

But, not all proteins are rendered completely useless when denatured. Many common food–based proteins are known to be somewhat denatured under normal cooking conditions; and, of course, these proteins still offer nutritional benefit. For example, an egg white which stiffens and turns white when cooked, is an example of a protein denaturing right before our very eyes. And our body is still able to break the egg white down into its constituent amino acids, and to absorb and utilize these amino acids for use as the building blocks of our muscles, organs, tissues, and metabolic enzymes.

So, as methods of processing and preserving foods exploded in the early part of the twentieth century, there was often a tendency among food producers to simply assume that any changes in protein structure which took place as a result of processing were unlikely to be particularly harmful.

But we now know better.

Quite logically, it turns out that the denaturation of proteins is dependent upon the severity of processing conditions. In other words, protein subjected to extremes of heat or pH simply incurs more damage. It’s now known that even many of the cooking methods we employ in our own homes can create known protein–based cancer–causing toxins. The National Cancer Institute reminds us that carcinogenic heterocyclic amines (HCAs) are often produced from muscle meats heated to high temperatures as in grilling, broiling, or barbecuing:

Article Link – Heterocyclic Amines in Cooked Meats.

Quote from the above article:

Research has shown that cooking certain meats at high temperatures creates chemicals that are not present in uncooked meats. A few of these chemicals may increase cancer risk…Frying, broiling, and barbecuing produce the largest amounts of HCAs because the meats are cooked at very high temperatures. One study conducted by researchers showed a threefold increase in the content of HCAs when the cooking temperature was increased from 200° to 250°C (392° to 482°F). Oven roasting and baking are done at lower temperatures, so lower levels of HCAs are likely to form, however, gravy made from meat drippings does contain substantial amounts of HCAs. Stewing, boiling, or poaching are done at or below 100°C (212°F); cooking at this low temperature creates negligible amounts of the chemicals. Foods cooked a long time (“well–done” instead of “medium”) by other methods will also form slightly more of the chemicals.

So, it’s very clear from the existing research that processing (either via cooking methods or industrial processing) is often the key determinant of whether a particular food is healthy or harmful.

And it shouldn’t come as a surprise to find out that the industrial processing of food components is known to produce a slew of unique protein toxins which could scarcely be created by normal cooking conditions. This particular fact is one which most producers of foods and protein–containing supplements wish their customers would ignore.

Are These Things Really Healthy?

The powdering of protein–containing products (like protein powders sold as nutritional supplements), and the extrusion of breakfast cereals (which allows cereal companies to create all sorts of “puffs,” flakes and shapes for grains) are two of the most prevalent examples of industrial processing techniques known to create particularly harmful denatured proteins.

Of course breakfast cereals and protein supplements are often marketed as healthy nutritional choices and there are even several companies who have combined the two, and who have begun marketing protein–fortified breakfast cereals in recent years. But as is so often the case, we’ll see that the marketing and the actual science tell different stories entirely.

When you think about it at a chemical level, it’s more than a bit naïve to assume that foods can be taken from their fresh state, heated to extremely high temperatures, exposed to chemical and physical processing, spray dried, and left to sit on a store shelf (or in a warehouse) for many months (if not years), and still maintain the beneficial nutritional properties of the fresh food. But isn’t this is exactly what the sellers of many breakfast cereals and protein powders want us to believe?

Sure enough, a closer look at the chemistry of the denatured proteins in such foods has revealed scores of protein–derived compounds with known or suspected toxicity. In turns out, as we at Integrated Supplements have repeatedly mentioned, that it takes great care (low temperature, stable pH, selective filters, etc.) to produce protein–containing products without denaturing protein, and without creating protein–based toxins.

AGEs And Aging

If you’ve read any of our previous articles on oxidized cholesterol, you know that cholesterol oxidation can occur both in our bodies (under conditions of oxidative stress), and in our food. And with oxidized cholesterol increasingly being implicated in a whole host of degenerative conditions from heart disease to cancer, it’s safe to say that we’ll want to avoid eating foods which contain oxidized cholesterol as much as possible. Hence our position that any health–conscious person should avoid any powdered product (like many protein powders) which contains cholesterol (as cholesterol in powdered form is particularly prone to oxidation).

And similarly to cholesterol, altered protein structures – resulting from the chemical interaction of proteins, sugars, and fats – can be produced both in our foods and in our bodies as well.

Scientists call these altered, denatured proteins glycation products (when the chemical changes proceed far enough, the resulting structures are called advanced glycation endproducts, or, AGEs, for short). Various glycation products and AGEs have been found to be consistently elevated in the body under conditions of aging and disease.

For example, a particular glycation product, called furosine, has been shown to be elevated in patients with Alzheimer’s disease and diabetes:

Study Link – Plasma protein glycation in Alzheimer's disease.

Quote from the above study:

Recent studies have suggested that formation of advanced glycation end–products (AGEs) in some brain proteins could be associated with Alzheimer's disease…Protein glycation was evaluated in plasma with a highly specific HPLC–UV technique, using furosine, which is the acid hydrolysis product of epsilon–deoxy–fructosyl–lysine Plasma furosine was almost two times higher in subjects with Alzheimer's disease (p<.005) than in controls, but still 50% lower than in diabetic patients (P<.02).

And similar to the glycation phenomenon which occurs in our body under the conditions of aging, certain types of food processing are known to result in the production of high amounts of furosine in some very common foods – two of the most notable for our discussion, again, being products often marketed specifically for their supposed health benefits – breakfast cereals and protein powders:

Study Link – Lysine availability is diminished in commercial fibre–enriched breakfast cereals.

Quote from the above study:

Furosine is a heat–induced marker for thermal treatment in foodstuffs and is directly related to the loss of lysine availability…Data showed a statistically significant effect of protein content, added–dietary fibre and physical form of the samples (flakes/puffed) on the level of furosine present in commercial breakfast cereals. The higher the protein content in the formulation, the higher were the furosine levels, regardless of the protein source. Significantly higher furosine levels were found in puffed commercial breakfast cereals.

The following study tested the furosine content of several commercially available sports supplements produced using milk based ingredients like whey protein isolate, whey protein concentrate, and casein. The furosine levels the researchers found in some of these products was shockingly high:

Study Link – Assessing nutritional quality of milk–based sport supplements as determined by furosine.

Quote from the above study:

Furosine content ranged from 2.8 to 1125.7 mg/100 g protein in commercial sport supplements being usually lower in samples containing mainly whey protein isolates or casein, as compared with whey protein concentrates. It is estimated that 0.1–36.7% of the lysine content is not available in this type of products. The use of high quality ingredients for the manufacture of sport supplements reveals important, since it could be the major source of protein intake of certain group of consumers in high or moderate training regime. Furosine is an appropriate indicator to estimate the nutritional quality of sport supplements. A reference value of 70 mg furosine/100 g protein content in dried sport supplements could be set up for controlling the quality of milk–based ingredients used in the formulation. Samples with higher levels are suspected of use of low quality milk–based ingredients or inappropriate storage conditions.

Note: Again, the products used in the above study were commercially available products – the same ones you’ll find on the shelves of your local supplement store. Although the products weren’t identified by name, the study results lend clear scientific validity to what we at Integrated Supplements have been saying all along – far too many companies within the nutritional supplement industry use the lowest quality raw materials they can find – ingredients which are decidedly unhealthy and at least mildly toxic. This is exactly why we created Integrated Supplements CFM® Whey Protein Isolate using the patented CFM® whey isolate raw material known to contain the lowest level of denatured protein (less than 1%) of any whey protein available. This is also why we are passionate about educating our customers on the inner–workings of the nutritional supplement industry.

Eat AGEs – Eat Aging

Knowing that glycation products formed in our body are, in part responsible for the degenerative effects of aging, and knowing that glycation products have repeatedly been associated with various degenerative diseases, it’s logical to think that perhaps eating these same glycated proteins may not be such a great idea if we value our long–term health.

So, the question naturally arises – what does the scientific literature have to say about the effects of actually consuming glycated proteins?

To put it simply, the effects aren’t pretty.  But you'd almost never find this fact out from the supplement industry.  There's simply too much money to be made by selling athletes and fitness enthusiasts one processed powder after another. 

For example, one of the most common questions posed by users of protein supplements is: can too much protein be harmful?

In a feeble attempt to address this question, the prevailing myth perpetuated by the supplement industry is that the body is able to “get rid” of whatever protein is consumed in excess. To some extent the body is able to rid itself of excess protein, but the common stance of the protein supplement crowd completely ignores the toxic effects of the denatured and glycated proteins commonly found in nutritional supplements.

In fact, according to the existing research, “getting rid” of glycated proteins is exactly what the body does not do efficiently – and this is what makes many protein–based nutritional supplements uniquely toxic relative to minimally–cooked protein–rich foods.

Actually eating large amounts of these denatured proteins and glycation products (as many users of protein powder, protein bars and ready–to–drink protein shakes unknowingly do), has been shown to add to the AGE burden of the body, and may be particularly detrimental to kidney function:

Study Link – Advanced glycation endproducts (AGEs) as uremic toxins.

Quote from the above study:

Dietary AGEs may contribute significantly to the total AGE load of the body, particularly in uremia.

It has also been found that eating glycated protein causes a major increase in systemic inflammation – including inflammatory disease markers such as C–reactive protein, even in healthy subjects:

Study Link – Diet–derived advanced glycation end products are major contributors to the body's AGE pool and induce inflammation in healthy subjects.

Quote from the above study:

Advanced glycation end products (AGEs) are a heterogeneous group of compounds that form continuously in the body. Their rate of endogenous formation is markedly increased in diabetes mellitus, a condition in which AGEs play a major pathological role. It is also known, however, that AGEs form during the cooking of foods, primarily as the result of the application of heat. This review focuses on the generation of AGEs during the cooking of food, the gastrointestinal absorption of these compounds, and their biological effects in vitro and in vivo. We also present preliminary evidence of a direct association between dietary AGE intake and markers of systemic inflammation such as C–reactive protein in a large group of healthy subjects. Together with previous evidence from diabetics and renal failure patients, these data suggest that dietary AGEs may play an important role in the causation of chronic diseases associated with underlying inflammation.

AGEs are also known to damage blood vessels, and many researchers have implicated AGEs as the major factors responsible for the vascular damage associated with kidney disease and diabetes. Building logically from this, some researchers have proposed a very plausible connection between the ingestion of glycation products in foods and the development of diabetes and subsequent diabetic complications like kidney disease:

Study Link – Possible link of food–derived advanced glycation end products (AGEs) to the development of diabetes.

Quote from the above study:

The formation and accumulation of advanced glycation end products (AGEs) have been known to progress at an accelerated rate under diabetes, and there is accumulating evidence that AGEs play a role in the development of diabetes by inducing islet beta cell damage and/or insulin resistance. Further, there are several animal studies to suggest that dietary AGEs are involved in insulin resistance, visceral obesity and the development of diabetes.

Denatured Protein – Not Just “Wasted”

In this, and the previous two Integrated Supplements Blog posts, we’ve shown you clear evidence that denatured and/or glycated proteins are very commonly found in nutritional supplements. We’ve shown you as well how these denatured proteins may either act directly as, or increase the production of, protein–derived toxins which may hasten the development of degenerative disease.

So, despite the common misconception that denatured proteins are merely inert, or “wasted,” the evidence is overwhelmingly clear that they are, instead, often mildly and cumulatively toxic.

There’s extensive research in the scientific literature regarding the many toxic substances which are formed when protein–containing foods are processed – but most supplement and food companies continue to almost completely ignore it. In bringing just a bit of this research to public attention, we hope that the message is clear: If you value your health, you simply cannot afford to ignore the effect of processing on protein quality.

We’ll have more to say about denatured and glycated proteins and their presence in nutritional products in upcoming Integrated Supplements Blog posts – stay tuned.

Neutralizing Protein-Derived Toxins With Soluble Fiber and Resistant Starch

In the previous Integrated Supplements Blog post, we looked at some of the protein–derived toxins which can be formed during the production of some protein powders commonly used as ingredients in nutritional supplements.

We saw how the harsh alkali chemicals, used in the production of protein powders such as soy protein and calcium caseinate, lead to the formation of various denatured, cross linked, and structurally altered protein–toxins like lysinoalanine.

And, we also saw how these toxic protein structures are able to “feed” the bad bacteria in our gastrointestinal tracts leading to the subsequent production of yet more protein–toxins such as phenols, cresols, indoles, amines, and ammonia – all of which are implicated in the development of colon cancer and various gastrointestinal disorders.

So, the existing research makes it clear that we should take every step possible to avoid consuming products made with overly–processed and denatured protein ingredients like soy protein, whey protein concentrate, and calcium caseinate.

And similarly, because of the high–heat processing (pasteurization) they must undergo, we should also take steps to eliminate prepared drinks (like ready–to–drink protein shakes, and soymilks) which are formulated using these same protein ingredients. High–heat processing has been shown to cause the production of shockingly high amounts of such protein–toxins, and, as evidence of their toxicity, these drinks have been shown to dramatically elevate cholesterol levels.

(Please see: Protein-Derived Toxins in Foods and Nutritional Supplements for more information, and for links to the relevant studies.)

But while these protein powders and drinks are probably the “worst–of–the–worst” in regard to the toxic byproducts they produce in our bodies, protein–derived toxins can also form from the ingestion of “ordinary” protein–containing foods as well.

In fact, one of the strongest scientific cases for vegetarianism is the fact that meat (especially red meats), can lead to the production of the very same protein–derived toxins within the gastrointestinal tract.

But, rather than needing to adhere to a strict vegetarian regime, recent research indicates, that if we consume certain protective nutritional elements, we may be able to largely eliminate the formation of protein–derived toxins from a high–protein diet.

To boot, such protective elements, namely, soluble fiber and resistant starch, not only eliminate protein–derived toxins – they can actually lead to the production of several protective elements by selectively feeding the “good” bacteria in our gastrointestinal tracts.

Soluble Fiber and Resistant Starch

As recently as several decades ago, scientists still thought of dietary fiber (and resistant starch – a unique type of dietary fiber) merely as the “inert” indigestible portions of plant–based foods. Even by the 1960’s when British surgeon, Denis Burkitt and colleagues coined the “fiber hypothesis” – the idea that high fiber foods may help to prevent colon cancer and other diseases of modern civilization – the beneficial effects of fiber were still simplistically assumed to involve fiber’s well–known effect of improving regularity.

But, while recent studies have failed to show a clear link between overall fiber intake and risk of gastrointestinal cancer. . .

Boston Globe Article Link – Doubts cast on fiber's effect on cancer

. . .other studies have shown that certain types of fiber may be particularly protective in this regard:

All Dietary Fiber Is Not Created Equal – Study Shows That Only Certain Types of Fiber Prevent Pre–Cancerous Changes of the Colon

So, rather than lumping all types of dietary fiber under one umbrella, some thinking scientists have begun to explore the varied effects of different types of fiber. As a result, the dietary fibers now suspected to be the most protective against protein–toxins, and the cancerous changes they cause, are the select few dietary fibers which are able to support the production of beneficial colonic flora (i.e. our “good” intestinal bacteria) – soluble fiber and resistant starch.

As we wrote about in the above–linked blog article, fermentable fibers feed beneficial bacteria which, in turn, produce a protective short–chain fatty acid called butyrate as a natural byproduct of their metabolism.

And, not only do these bacteria produce butyrate, which helps to nourish and protect the cells of the colon, but, as it turns out, these same beneficial bacteria are able to significantly reduce the production of protein–based toxins, as was found in this study:

Study Link – Resistant starch lowers fecal concentrations of ammonia and phenols in humans.

Quote from the above study:

These results suggest that RS (resistant starch) significantly attenuates the accumulation of potentially harmful byproducts of protein fermentation in the human colon.

In fact, It’s likely to be our beneficial intestinal flora (and not just the fiber itself) which neutralizes the production of toxic metabolites from dietary protein.

As mentioned above, some of the protein we eat is able to travel all the way to the colon without being digested or absorbed. In the presence of a low–fiber diet, relatively “bad” bacteria will predominate in the colon, and these bacteria are able to metabolize this protein into the previously–mentioned toxic substances such as phenols, cresols, indoles, amines and ammonia.

But, on the other hand, if we supply our good bacteria with abundant amounts of soluble fiber/resistant starch, they (and not the bad bacteria) use the protein to grow and flourish in the intestines.

In other words, in the presence of certain types of fiber, beneficial bacteria are able to metabolize the nitrogen–containing components of undigested protein for their growth – thus simultaneously lowering the burden of toxic metabolites, (phenol, cresol, and ammonia); while increasing the production of beneficial substances like butyrate and other short chain fatty acids.

Scientists call the beneficial bacteria in our colon a “nitrogen sink” – meaning, a biomass which is able to metabolize nitrogen compounds (proteins) towards beneficial ends instead of toxic ones. While it often goes unrecognized, this natural form of “bioremediation” represents a stunning example of biological synergy, essential to our optimal health.

Feeding The Beneficial Bacteria

As we’ve repeatedly mentioned, only some types of fiber help to support the growth of the beneficial bacteria in our intestines, and this fact helps to explain why, despite effective marketing, certain types of fiber (i.e. some bran cereals), and intestinal “cleansers” and laxatives (both herbal and pharmacological) probably do relatively little to improve overall gastrointestinal health.

The synergy of protein and soluble fiber/resistant starch in supporting a healthy intestinal ecosystem is but one of countless examples in nutrition of the fact that nutrients never work in isolation from one another. Failure to grasp this concept has led to a great many dead ends in nutritional research where isolated nutrients continually fail to live up to their initial hype.

But, an integrated approach is the cornerstone of our philosophy at Integrated Supplements, and it’s just one of the reasons why we produce 100% Natural CFM® Whey Protein Isolate – the highest quality, undenatured whey protein available – along with Fiber Balance™, a smooth and delicious combination of 5 types of dietary fiber and resistant starch – all known to support the proliferation of healthy intestinal bacteria.

As research like that posted above continues to mount, our approach is consistently and repeatedly being validated. And as we continue to put the pieces of the nutritional puzzle together, we can confidently state that Integrated Supplements truly is Nutrition For Your Full Human Potential.

We’ll have more research soon – stay tuned.

Related Articles:

Can Some Types of Dietary Fiber Extend Your Life?

All Dietary Fiber Is Not Created Equal - Study Shows That Only Certain Types of Fiber Prevent Pre-Cancerous Changes of the Colon

Protein-Derived Toxins in Foods and Nutritional Supplements

With protein powders, protein bars, and ready–to–drink protein shakes currently flooding both the nutritional supplement and mainstream markets, people are often surprised to learn that many of these products are not the healthy, nourishing snacks they’re promoted to be. In fact, as scientists continue to study the effects of protein processing on nutritional quality, some interesting studies have emerged showing that many of the unnatural proteins formed in the production of modern foods and supplements are likely to be at least mildly toxic.

Scientists have long studied various toxic substances which are known to be formed during the production of protein–containing powders; and though it’s likely that many protein–based toxins still have yet to be discovered, there is enough evidence in the scientific literature to make any rational, thinking person wary of certain so–called “health foods”.

We’ve shown elsewhere, how the alkali–treatment of proteins (including common nutritional supplement ingredients such as soy protein isolate, and calcium caseinate), leads to the production of unnatural cross–linked amino acids like lysinoalanine (LAL). Lysinoalanine has been shown to have many negative effects on digestion and overall metabolism:

Study Link – Influence of feeding alkaline/heat processed proteins on growth and protein and mineral status of rats.

Quote from the above study:

The data suggested that LAL, an unnatural amino acid derivative formed during processing of foods, may produce adverse effects on growth, protein digestibility, protein quality and mineral bioavailability and utilization. The antinutritional effects of LAL may be more pronounced in sole–source foods such as infant formulas and formulated liquid diets which have been reported to contain significant amounts (up to 2400 ppm of LAL in the protein) of LAL.

Study Link – Interaction of lysinoalanine with the protein synthesizing apparatus.

Quote from the above study:

These results indicate that LAL is an inhibitor of both prokaryote and eukaryote lysyl–tRNA–synthetase. Furthermore, it is incorporated into protein. Both of these actions can be factors in the nephrotoxicity of this common food contaminant.

So, according to the above studies, processed proteins containing lysinoalanine:

• Inhibit growth

• Inhibit protein synthesis

• Inhibit digestion

• Inhibit mineral absorption

• May harm the kidneys

• And impart anti–nutritional effects

It’s more than a bit ironic then, that lysinoalanine (and many similar toxic “anti–nutrients”) can so commonly be found in the ingredients used by the nutritional supplement industry in an ever–increasing number of protein powders, bars, and drinks.

Decades ago, research into the toxic effects of protein processing centered on ways to create the least toxic infant formulas, or the least toxic enteral feeding formulas for hospital settings. Industrially processed proteins were never thought of as healthy, and the products in which they were used were produced for situations in which even poor nutrition was clearly better than dying of starvation. But, in recent years many of the same (or very similar) protein ingredients have been promoted as dietary staples for health–conscious consumers. Since so many people are currently being misled by flashy advertising and fancy product packaging, it’s important to set the record straight on the potentially harmful effects of some of the proteins found in nutritional powders, drinks, and bars.

The Effects of Processing

In addition to alkali–treatment, toxins like lysinoalanine can also be formed as a result of the high heat processes now commonly used to pasteurize milk. Ultra heat treatment, or ultra high temperature (UHT) and sterilization processes are now able to produce milk and milk–based products (like protein drinks) which require no refrigeration – but the formation of lysinoalanine in such products has been found to be shockingly high.

Study Link – Determination of lysinoalanine in foods containing milk protein by high–performance chromatography after derivatisation with dansyl chloride.

Quote from the above study:

The LAL contents analysed in raw and pasteurised milk ranged from 4 to 24 and 17 to 69 mg kg−1 crude protein, respectively. Compared to that, UHT–treated milk and sterilised milk showed higher LAL levels up to 186 and 653 mg kg−1 crude protein, respectively.

And if milk itself contains such a high LAL content when high–heat processed, it’s certain that protein drinks will fair much worse. Unlike fresh milk, the (alkali–treated) powders used in the production of protein drinks already contain significant lysinoalanine, even before further heat treatment:

Study Link - Lysinoalanine Content of Formulas for Enteral Nutrition

Quote from the above study:

. . .the preparation of caseinates and the thermal stabilization of the end products are the two steps more favorable for the formation of LAL.

And it’s important to note that lysinoalanine is far from the only toxic product formed by heat and pH treatment of proteins – it’s just one of the most studied:

From: Lysinoalanine in Foods and Antimicrobial Proteins

Heat and alkali treatment of food proteins widely used in food processing results in the formation of crosslinked amino acids such as lysinoalanine, ornithinoalanine, lanthionine, and methyl lanthionine, and concurrent racemization of L–amino acid isomers to D–analogs.

Still Think Your Protein Drink is Healthy?

Although many of the byproducts produced by protein processing have yet to be studied individually, there is clear evidence in the scientific literature that heat–treated protein drinks (the kind very commonly available, from soymilks, to protein–containing sports drinks) impart a cumulatively toxic effect.

The following study showed that both soy and casein protein, when subjected to ultra heat treatment (UHT) caused a significant elevation in LDL cholesterol levels.

Study Link – Ultra heat treatment destroys cholesterol–lowering effect of soy protein.

Quote from the above study:

Unexpectedly, at the end of the study, low–density lipoprotein cholesterol concentrations were significantly increased compared with baseline in all study groups. The magnitude of this increase (17–19%) was similar in all active and placebo study groups. Soy protein supplements previously shown to be effective in reducing serum cholesterol had in this study no such lipid–lowering effect after ultra heat treatment.

A 17% to 19% increase in LDL cholesterol as shown in the above study is an enormous elevation, and represents a major threat to health. The study authors concluded that the altered protein structures resulting from heat treatment were responsible.

Note: In the time since we first wrote about the above study, we’ve heard from quite a few people who were able to tie their high cholesterol levels with their consumption of ready–to–drink protein shakes. Such drinks are currently being promoted by professional athletes in flashy television commercials – which is a good indication that their popularity is sure to increase. But sadly, the negative health–effects of these drinks will probably never be suspected by the all–too–trusting public. As a reader of the Integrated Supplements blog, you, on the other hand, know the truth. Spread the word.

Altered Proteins and Intestinal Bacteria

Unlike native, undenatured proteins (protein which the body recognizes as nutritive), these foreign protein–containing substances are apt to be poorly utilized and absorbed. When such proteins are absorbed into the bloodstream, they’ve been shown to tax liver and kidney function as the body attempts to rid itself of them (an elevation in cholesterol level is sometimes indicative of the body’s response to a toxic threat, which may explain the above–mentioned cholesterol increase in response to UHT–treated proteins).

Any factor which impairs the nutritional quality of a protein will also impair protein absorption. And if proteins aren’t absorbed properly, they don’t simply pass through the body unscathed. Rather, in their journey through our digestive tract, altered proteins are likely to be fermented into various other toxic compounds such as phenols, cresols, indoles, amines and ammonia by the bacteria which inhabit the colon. This is one reason why so many protein supplements (including many of the lower–quality whey protein supplements) often cause gas, bloating, cramping, or an upset stomach – this phenomenon is due to the fermentation of protein by colonic bacteria, and is not simply due to lactose intolerance as some people believe.

Study Link – p–cresol: a toxin revealing many neglected but relevant aspects of uraemic toxicity.

Quote from the above study:

P–Cresol is an end–product of protein breakdown, and an increase of the nutritional protein load in healthy individuals results in enhanced generation and urinary excretion. The serum p–cresol concentration in uraemic patients can be decreased by changing to a low–protein diet. p–Cresol is one of the metabolites of the amino acid tyrosine, and to a certain extent also of phenylalanine, which are converted to 4–hydroxyphenylacetic acid by intestinal bacteria, before being decarboxylated to p–cresol (putrefaction).

The action of intestinal bacteria on proteins (especially overly–processed, altered, and poorly absorbed proteins) may explain why the consumption of certain protein–rich foods (processed meat, for example) has often been implicated in the development of colon cancer:

Study Link – Meat Consumption and Risk of Colorectal Cancer.

Quote from the above study:

Our results demonstrate the potential value of examining long–term meat consumption in assessing cancer risk and strengthen the evidence that prolonged high consumption of red and processed meat may increase the risk of cancer in the distal portion of the large intestine.

But despite the claims of some vegetarians that meats are the sole source of such protein–derived toxins, it seems that any overly processed, extensively heated, or denatured protein is apt to produce significant amounts of toxic byproducts in the intestines. The following study found that heat–treated (thermolyzed) casein, egg white, and soy proteins (the kinds of protein sources commonly found in dietary supplements) all caused a marked increase in the production of protein–derived intestinal toxins.

Study Link – Colonic Protein Fermentation and Promotion of Colon Carcinogenesis by Thermolyzed Casein.

Quote from the above study:

We found that the thermolysis of casein reduces its digestibility and increases colonic protein fermentation, as assessed by fecal ammonium and urinary phenol, cresol, and indol–3–ol. Thermolysis of two other proteins, soy and egg white protein, also increases colonic protein fermentation with increased fecal ammonia and urinary phenols.

Although the heat–treated proteins didn’t lead to the development of colon cancer in the above study (which actually surprised the researchers), the formation of toxic byproducts was significantly increased in animals who consumed the heat–treated protein supplements.

Studies by other researchers have shown that heat–treated casein does indeed lead to the production of aberrant crypt foci (ACF) – well–known precursors to colon cancer development.

Study Link – Promotion of aberrant crypt foci and cancer in rat colon by thermolyzed protein.

Quote from the above study:

Thermolyzed casein promotes early colonic precursor lesions in a dose–dependent and thermolysis time–dependent manner; thermolyzed casein also promotes colon cancer.

Researchers have also found that feeding mice and rats cooked combinations of casein, sugar, and fat led to the formation of microadenomas in the colon (microadenomas are small tumors, a step closer to colon cancer development than aberrant crypt foci.)

Study Link – Promotion of Colonic Microadenoma Growth in Mice and Rats Fed Cooked Sugar or Cooked Casein and Fat.

Quote from the above study:

. . .a diet containing 20% of cooked sucrose, or 40% of casein and beef tallow cooked together, promotes the growth of colonic microadenomas in initiated mice and rats, and would appear to contain promoters for colon cancer.

Given the above study, it’s truly frightening to note that one of the most popular ready–to–drink protein shakes in the country right now is a “muscle milkshake” which contains particularly high amounts of casein, sugar, and fat. By law, all such drinks must be “cooked” or pasteurized when they are produced – yet it’s doubtful that the millions of people consuming this drink have the faintest idea that they may be dramatically increasing their risk of colon cancer in the process.

Although the research presented here is just the tip of the iceberg in the field, we can see clearly that the heat and alkali–treated protein ingredients found in nutritional supplements don’t offer much in the way of actual nutrition – and that they very well may be mildly toxic.

Excluding protein ingredients like soy protein isolate, caseinate, and whey protein concentrate, as well as any ready–to–drink protein shakes, from our daily routine is a good first step. But even quality sources of protein from fresh foods may be able to form toxic substances in our body if we don’t take steps to protect ourselves. In the next Integrated Supplements blog article, we’ll take a look at some of the strategies we can employ to neutralize these toxins, and reap the full benefits of a healthy diet, and intelligent supplementation.

Stay Tuned

Related Articles:

Casein - The Slow Digesting Protein - Not So Fast

Study Finds Heat-Processed Protein Drinks Send "Bad" Cholesterol Skyrocketing

 

Can Some Types of Dietary Fiber Extend Your Life?

While life–extension research often centers upon some of the most cutting–edge procedures in biotechnology, recent research indicates that even some incredibly simple nutritional strategies may have the ability to extend lifespan as well.

A recent study published in the British Journal of Nutrition was the first ever to show that supplementation with two simple dietary fibers, inulin and oligofructose, extended the lifespan of test animals by over 30%.

Study Link – Effects of lifelong intervention with an oligofructose–enriched inulin in rats on general health and lifespan.

In the above study, researchers tracked 60 male and 60 female 3–month old rats. Half of the animals in each group were fed the standard control diet, and half a diet enriched with the prebiotic fibers inulin and oligofructose.

In the group receiving the inulin and oligofructose, the researchers noted a significant decrease in bodyweight, cholesterol, and triglycerides. And, as relates to lifespan, the researchers found:

After 18 months:

• None of the rats receiving the additional fiber had died.

• 15% of the rats in the control group had died

After 24 months:

• 38% of the rats receiving additional fiber had died.

• 59% of the rats in the control group had died.

All told, male and female rats receiving the fiber mixture exhibited an average increase in lifespan of over 34%.

How Could Prebiotic Fibers Increase Lifespan?

Unlike some other types of dietary fiber, inulin and oligofructose are known as prebiotics – a term coined relatively recently to connote types of fiber which encourage the growth of certain types of beneficial bacteria in the intestines. Not all types of fiber have this effect, but inulin and oligofructose are two of the most potent prebiotics known – our first clue as to the potential mechanism of their effectiveness in increasing lifespan.

In aging, many factors can cause the level of beneficial bacteria like lactobacillus and bifidobacteria to decline, which leaves other bacteria free to run amok in the GI tract. Many of these other bacterial species are known to produce toxic metabolites like indoles, phenols cresol, amines and ammonia from the foods we eat. In the absence of lactobacillus and bifidobacteria, the relatively harmful bacteria can multiply unabated, producing an ever–increasing amount of these toxic metabolites.

A Brief Word on Internal Cleansing and Detoxification

Many conventional physicians and health authorities still scoff at the idea that “normal” bowel bacteria produce toxins in sufficient amounts to impact health, but the research is accumulating indicating that this is indeed the case. In addition to the research linked above, we previously showed you research by the Soviet gerontologist VV Frolkis, who was able to similarly increase the lifespan of the rats he studied by adding the highly adsorptive substance, activated charcoal, to their diets.

Internal Cleansing - The Truth About The Most Controversial Subject in Natural Health

And considering that neither prebiotic fibers nor charcoal are even absorbed into the bloodstream, and that both act to lessen the burden of known intestinal toxins (prebiotic fibers by increasing the “good bacteria,” and charcoal by latching on to the toxins directly), it’s reasonable to assume that the life–extending capacity of both substances is directly related to some sort of “detoxifying” effect.

It should be noted too, that while intestinal toxins do exist, many common herbal and nutritional “detox” products sold as dietary supplements often contain only stimulatory herbs, destined to impart little more than a laxative–effect. Such products often do little to actually restore bacterial balance in the intestines, or to minimize toxic exposure in the long–term. These products could actually make the situation worse, as the intestines often become sluggish after chronic stimulation with such laxatives.

Life Span Studies

In medicine and nutrition, it’s easy to place entirely too much emphasis on markers of health and disease – those numbers on a blood test or lab report which we, or our physician, often try to coax into the “normal” range by any means necessary.

As a perfect example, recent research has raised concerns that a popular cholesterol–lowering drug combination may not prevent heart–disease risk, and may even be associated with an increased incidence of cancer.  Such findings should give us fair warning of the dangers of becoming too myopically focused on our levels of mere biological markers like cholesterol.

Article Link – Cholesterol Drug Zetia Doesn't Benefit Health: Study

Quote from the above study:

The long–awaited results of a trial of Zetia, a cholesterol–lowering drug prescribed to about a million Americans, shows the drug confers no medical benefit to users.

In fact, the pace at which artery–clogging plaques formed within vessels almost doubled in patients taking Zetia (ezetimibe) along with another cholesterol–lowering drug, Zocor (simvastatin), compared to those taking Zocor alone, the study found.

Study Link – Intensive Lipid Lowering with Simvastatin and Ezetimibe in Aortic Stenosis.

Quote from the above study:

Cancer occurred more frequently in the simvastatin–ezetimibe group (105 vs. 70, P=0.01).

The ability to be blindsided by such unforeseen effects when addressing only disease markers is why life span studies are among the most valuable in nutritional research – they help us to answer the only health question most of us really care about – what steps can I take to live a long, healthy, vibrant life?

In life span studies, when animals in one group begin to die prematurely and animals in the treatment group live significantly longer, this can give us some truly meaningful clues about the nature of aging in general, as well as clues about which foods and nutritional supplements truly deliver on their promise of supporting health, and which ones are just driven by speculative hype.

And the research keeps becoming clearer – prebiotic fibers, precisely because they support healthy microbial balance in the intestines, may be able to support our health in ways few people have previously imagined. Far from just supporting gastrointestinal health, such fibers may be a useful cornerstone of any nutritional program designed to forestall the ravages of aging.

Note: Integrated Supplements Fiber Balance™ contains both inulin and oligofructose, along with Fibersol 2®, and beta glucan from oats – all fiber sources carefully chosen for their ability to support a healthy microbial balance in the intestines.

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All Dietary Fiber Is Not Created Equal - Study Shows That Only Certain Types of Fiber Prevent Pre-Cancerous Changes of the Colon

Thanks in large part to a collaborative effort by major television networks, media members and prominent celebrities, it's probable that most of us will be hearing a lot more about colon cancer in the coming weeks.

And it's about time.

Unbeknownst to many Americans, colon cancer is the second leading cause of cancer death in America, behind only lung cancer.

According to the National Cancer Institute:

• An estimated 150,000 Americans are predicted to be diagnosed with colon or rectal cancer in 2008, and 50,000 are predicted to die from the disease.

• Regular screenings for colon cancer are important. If caught early, the 5-year survival rate for colon cancer is among the highest of all cancers.

• Dietary and lifestyle factors play particularly major roles in the development of colon cancer.

And not surprisingly, the dietary and lifestyle recommendations often made for colon cancer prevention are pretty straightforward – they echo the stock recommendations we’ve been receiving from health authorities for decades:

• Find ways to reduce stress

• Exercise

• Eat a low-fat, high fiber diet rich in fruits and vegetables

In fact, we’ve all heard this advice so many times, that there’s a tendency to let it go in one ear and out the other. So, perhaps we owe it to ourselves to take a deeper look at exactly how the foods we eat can affect the health of our intestines - and in particular, it may help us to question our assumptions about dietary fiber.

Fiber – More Than Just “Roughage”

Most of us simply think of fiber as “nature’s broom,” that indigestible part of plant food that “sweeps” our insides and keeps us regular. But we now know that certain types of fiber have much more intricate and fascinating effects than just this. When we look a little closer at the research, we find that certain types of fiber may be particularly protective of the delicate tissue of the intestines, while other types of fiber may not be.

This may be why, historically, scientific studies have produced oddly conflicting results when looking at the role of fiber in preventing colon cancer.

All Fiber is Not Created Equal

But as scientists have recently begun examining the effects of different types of fibers, their findings are helping to put the big picture of fiber into clearer focus. The researchers who conducted the following study, for example, found clear evidence that only fibers which increase the production butyrate in the colon are protective against pre-cancerous changes:

Study Link - Only fibres promoting a stable butyrate producing colonic ecosystem decrease the rate of aberrant crypt foci in rats.

Quote from the above study:

. . .only RS and FOS produced large amounts of butyrate, with a trophic effect in the large intestine. No difference in mucosal proliferation between the diets was noted at this time. In the subsequent experiment one month later, fewer aberrant crypt foci were present in rats fed high butyrate producing diets . . . A stable butyrate producing colonic ecosystem related to selected fibres appears to be less conducive to colon carcinogenesis.

We’ve written previously in The Integrated Supplements Newsletter, and blog about how soluble fibers (more correctly defined as fermentable fibers), are unique in being able to support the growth of good bacteria in the intestines. These good bacteria, which feed on soluble fiber, produce substances called short chain fatty acids (SCFAs) as a byproduct of their metabolism. It’s these SCFAs (especially butyric acid, or, butyrate) which are now thought to exert protective effects upon the cells of the colon.

The researchers who conducted the above study fed rats three different types of dietary fiber:

• Wheat Bran (mostly insoluble, non-fermentable fiber)

• Resistant Starch (RS, a fermentable fiber)

• FOS (Fructo-oligosaccharides, a fermentable fiber)

They found that only resistant starch (RS) and FOS – two fibers able to increase the production of the SCFA, butyrate, by colonic bacteria, prevented the production of aberrant crypt foci in rats injected with the known colon cancer-promoter, azoxymethane. In this study, wheat bran had no protective effect.

Note: aberrant crypt foci are clusters of abnormal tube-like glands in the lining of the colon. Their formation precedes the formation of colon polyps, and they are the earliest noticeable pre-cancerous change in the intestines.

So, while our bowl of raisin bran or fiber cereal in the morning may be helping to keep us regular, it’s probable that these fiber sources alone may not be offering us the full protective benefits which dietary fiber has to offer.

Note: Some fruits and vegetables, like bananas and onions respectively, are known to contain sources of fiber like those shown in the above study to increase butyrate production. Cereal fibers, although they comprise a major percentage of fiber consumption in this country, may not be quite as protective as we’ve been led to believe:

Study Link - Fruit, vegetables, dietary fiber, and risk of colorectal cancer.

Quote from the above study:

Individuals who consume very low amounts of fruit and vegetables have the greatest risk of colorectal cancer. Relatively high consumption of cereal fiber does not appear to lower the risk of colorectal cancer.

How Does Butyrate Work?

Butyrate is known to inhibit an enzyme involved in the regulation of genes known as Histone Deacetylase (HDAC). When this enzyme is inhibited by butyrate, tumor-suppressor genes are activated, and this may account for the potential protective effect of butyrate, and certain types of dietary fiber.

So, indirectly, fiber affects the health of our intestinal cells right down to the genetic and molecular level. And to think, it wasn’t all that long ago when scientists themselves thought of dietary fiber simply as the “roughage” we needed to keep us regular.

The Picture Becomes Clearer

While the causes of colon cancer are complex and multi-faceted, research like this makes the picture at least a little clearer. If you’re like the vast majority of Americans and you don’t consume sufficient fiber on a daily basis, or if you rely on cereal grains for the majority of your fiber intake, you may want to rectify this situation immediately - paying particular attention to take in sources of fiber which support the healthy intestinal bacteria, and the production of butyrate. Probiotic supplements, or cultured foods like yogurt are likely to be valuable as well.

Eating a varied diet of fiber-rich foods is, of course, important; but, even with the best diet, it can certainly be difficult to take in the recommended 25 to 35 grams of fiber we need each day. Making this task a little easier is why we created Fiber Balance™, an all natural blend of 5 types of fiber including inulin, FOS, and resistant starch – fiber sources which are all known to support the growth of the good bacteria, and to increase butyrate levels in the colon.

We often recommend that people mix Fiber Balance™ right into yogurt – with the combination of yogurt’s probiotic cultures and the butyrate-producing fibers in Fiber Balance™, you could hardly imagine a more potent one-two punch for supporting gastrointestinal health.

And the combination tastes so good, that you’ll probably have a hard time believing that this little snack is really on the cutting edge of scientific nutrition.

About Us: At Integrated Supplements, our goal is to bring you the wellness information and products you need to live your life to the fullest. We are dedicated to producing the highest quality, all natural nutritional supplements; and to educating the world on the health promoting power of proper nutrition. You can find out more by visiting: www.IntegratedSupplements.com

These statements have not been evaluated by the FDA. No Integrated Supplements product is intended to diagnose, treat, cure or prevent any disease.

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