Fish Oils: Ethyl Ester versus Triglyceride forms

Low strength natural fish oils are in triglyceride (TG) form, as are most natural oils. To purify the oils by removing impurities and less desirable fatty acids and to concentrate the EPA and DHA fatty acid components, molecular distillation is used.  This process allows the oil to vaporize at low temperatures under pressure and is also known as vacuum distillation. The resulting vapor is collected and cooled, stratifying into distinct layers of fatty acids. This allows a purer esterified oil (called an ethyl ester form, or EE) with higher levels of EPA-DHA than crude fish oils and removal of triglycerides and cholesterol as well as other undesirable components. 

Some companies like to add triglycerides back in; this dilutes the fish oil concentrate by about 20% and the process also introduces mono- and di-glycerides, which don’t exist in natural fish oils to a significant degree but are thought responsible for higher absorption levels of this reconverted triglyceride form (rTG) oil over natural triglyceride and ethyl ester forms. If no triglycerides are added back, the body’s own store of triglycerides will be used to bond to the fatty acids after absorption, potentially lowering serum triglycerides more than an rTG oil. 

Absorption from our guts is always in the form of free fatty acids, so the oil’s original triglycerides are typically discarded during digestion and reattached later from body stores. This lowers the potential of the TG or rTG oils to lower triglycerides already in our bodies since they introduce additional triglycerides, which may be absorbed either into the body (adding more triglycerides into the liver) or into fiber or other materials that carry cholesterol out through the stool (potentially reducing the removal of cholesterol by competitive absorption). 

The prescription fish oils are in the ethyl ester form, not triglyceride form, because of the higher purity and higher strength of EE fish oils over TG or rTG forms resulting in better study outcomes on cardiovascular health measures. 

Krill oil is distinct because of its phospholipid matrix that greatly enhances omega-3 absorption more than the EE, TG, or rTG forms of fish oil.

Fish Oils: ethyl ester or triglyceride or...?

Most fish oils today are molecularly distilled, changing them from their natural triglyceride forms to ethyl ester (esterified) forms.

Anything stronger than a natural strength fish oil (up to about 30% EPA+DHA combined) is typically concentrated by molecular (vacuum) distillation to allow vaporizing at low temperatures, in the process converting to the ethyl ester form. This allows separation of the fatty acid constituents in order to add back some of the desired omega-3 fatty acids in order to concentrate them up to 60% or higher levels of the oil. This is accomplished by removing undesired fractions that were separated by the distillation, such as cholesterol, triglycerides, and various other fatty acids.

Because of the warming oceans, the naturally occurring amount of omega-3 fatty acids in most fish have declined from historically about 30% to somewhat less. Due to this change, most fish oil supplements containing 180 mg. of EPA and 120 mg. of DHA (300 mg. combined in a 1,000 mg. fish oil capsule) now need to spike the potencies by adding additional EPA and DHA fractionated from the original oils by molecular distillation. It is now unusual to find even a low strength fish oil capsule that is not at least partially molecularly distilled into ethyl ester forms. 

Some of these distilled oils are then partially reconverted to a triglyceride form in a process called reconversion that involves adding back 20% or more triglycerides to the esterified fatty acids to try to reattach the triglycerides to the fatty acids with enzymes. This imperfectly produces a highly processed combination of both triglyceride and mono-and-diglyceride forms of omega-3 with many of the original oil’s natural constituents deliberately removed (cholesterol, omega-6, omega-9, stearates, et al). This newly engineered combination is called a reconverted triglyceride form (rTG) containing typically at least 60% triglyceride form fatty acids that’s distinct from the original triglyceride (TG) form, but is as far from the original triglyceride form as can be produced by intentional chemical manipulation. Numerous brands offer this rTG form and inaccurately call it a natural triglyceride form, when it is in fact far removed from that oil.

This is done because of a prevailing and largely disproven belief that the natural triglyceride form is best. That's certainly untrue for cardiology and the form has recently been shown to be largely irrelevant to absorption and efficacy in general. 

The Facts About Omega-3 Fatty Acids and Increased Prostate Cancer Risk

A study released this week, “Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial,” published in the Journal of the National Cancer Institute (JNCI)) suggests that the omega-3 essential fatty acids EPA, DPA, and DHA - but not the omega-3 fatty acid ALA, found in flax, chia, hemp seeds, and nuts that have repeatedly been shown to lower prostate cancer rates - are somehow associated with increased risks of high-grade prostate cancer. At the same time, higher amounts of normally harmful trans fats in these subjects were associated with lower rates of advanced prostate cancer. [1] Because of the known limitations of this particular kind of study, all of these reported results were completely unproven, highly questionable, and highly unlikely to be true.

What kind of study was this? It is data mining of a previously published population study in which important variables and endpoints for fish oil's relationship to prostate cancer were not controlled, nor any cause and effect demonstrated. Because it is a secondary analysis of a largely epidemiological (population) study, it represents the lowest level of evidence in human studies because most relevant variables, confounding factors, and clinical endpoints are not systematically collected for proper analysis as they would be in an actual controlled clinical trial. Instead, the limited goal was to look for possible associations that were admittedly not rigorous enough to be considered as actual evidence of a causal relationship. As a preliminary study, it was consciously designed only to raise questions, rather than to provide answers, and it did accomplish that goal but also created a messy splash of misleading and over-emphatic headlines inaccurately suggesting that this one study somehow trumps many more robust clinical trials. So much for the media knowing of and respecting the Scientific Method. [2]

Dr Marilyn Glenville PhD, the UK’s leading nutritionist specializing in women’s health and former President of the Food and Health Forum at the Royal Society of Medicine, has noted some deficiencies in the current JNCI report; some examples: [3]

• “This is not a randomised controlled trial but a trial comparing Omega 3 levels in men with prostate cancer with healthy men. The men with prostate cancer had higher levels of Omega 3. But you cannot extrapolate cause and effect from this finding. It is like saying that if the majority of men with prostate cancer played tennis compared to healthy controls then tennis could trigger prostate cancer.”
• In 2009 the Harvard School of Public Health reported that “Omega 3 deficient diets cause up to 96,000 preventable deaths a year in the US. The researchers estimated the number of deaths resulting from 12 preventable causes and Omega 3 deficiency ranked as the sixth highest killer of Americans. A deficiency in these fats was classed as a bigger killer than high intake of trans fats.” [4]
• “…there are many cultures such as the Japanese who eat high amounts of oily fish containing Omega 3 fatty acids and yet have one of the lowest prostate cancer death rates in the world.”

Duffy MacKay, N.D., vice president, scientific and regulatory affairs of the Council for Responsible Nutrition, also noted some concerns with the report: [5]

• “Hundreds of studies over the past two decades have shown omega-3 fatty acids to have positive effects associated with cardiovascular health, perinatal health, inflammation, cognitive function, or cancer. Collectively, this body of research serves as the basis for numerous recommendations from respected organizations, scientific boards and healthcare practitioners that Americans get omega-3 fatty acids in their diets.”
• “While we encourage researchers to continue to study omega-3 fatty acids with an open mind, it is counterproductive when studying nutrition for researchers to promote their study as if it were the only piece of research that counts. In this case in particular, it is especially disingenuous for the researchers to make the kinds of assertions we've seen in the press, given their results are in stark contrast to previous epidemiologic studies that not only demonstrate no correlation between omega-3 consumption through fish and/or supplementation and the risk of prostate cancer, but in many cases also showed a protective effect against prostate cancer.”
• “One should also consider whether this study could have simply been measuring a biomarker reflecting recent intake of fish or fish oil supplements in a group of high risk cancer patients that had been told to increase their EPA and DHA levels, as compared to a group of non-cancer patients that had not been told to consume more EPA and DHA. Plasma levels of EPA and DHA reflect very recent intake and are considered a poor biomarker of long term omega-3 intake especially when compared to red blood cell levels, which reflect medium term intake. A single fish oil dose (or hearty serving of fish at lunch) results in >100 percent increase in plasma omega-3 levels. So looking at plasma levels in healthy and sick people may only provide insight into the recent habits of these individuals.”
• “The American Heart Association, the World Health Organization (WHO), the U.S. Institute of Medicine’s Food Nutrition Board (IOM FNB) and the 2010 Dietary Guidelines all have current policies advising Americans to eat more fatty fish to get the benefits of omega-3 fish oils. It is highly unlikely this one study will change that advice. Omega-3s can also be obtained by taking one of the many supplement products on the market. For those consumers who have concerns about prostate cancer or other questions about omega-3 fatty acids, we recommend speaking with your doctor or other healthcare practitioner.”

If you are a man and believe this report, then you’ll probably want to eat partially hydrogenated artificial trans fats instead of omega-3 fats for prostate health; though that change would greatly increase your risk of suffering far deadlier cardiovascular diseases, based on evidence from many clinical trials. But that would be ridiculous. In fact, many cultures around the world consume far more fish oil than Americans without having increased risks of aggressive prostate cancer; these include the Inuit people ("Eskimos"), Scandinavians, Southeast Asians, Pacific Islanders, Japanese, Filipinos, and others. 

In any case, in the absence of proper controls or any evidence of causation, we actually can’t know what these study results really mean. For example:

• Were DHA levels related to diet, supplementation, or both?
• Were fish and/or fish oils perhaps consumed as a deliberate health choice because of prior knowledge of prostate issues, rather than actually causing or aggravating those issues? In other words, could the consumption represent an attempt to improve a pre-existing condition by improving one’s nutritional status and be unrelated to the disease itself? Perhaps even suggested by medical teams as potentially helpful for patients' diet?
• If they had been collected, what would key inflammatory and oxidative markers, that are much likelier to be related to prostate health problems than long-chain omega-3 fatty acids such as DHA, have told us about these men’s state of health and disease?
• Where is the biochemical evidence that DHA itself may negatively contribute to prostate concerns? None is presented, even theoretically.

The Global Organization for EPA and DHA Omega-3s (GOED) also criticized these and numerous other some aspects of the JNCI report, among them these important points: [6]

• “The difference in mean blood plasma phospholipid fatty acids blood level for omega-3s was 4.66% in the combined cancer group versus 4.48% in the control. They are basing their results on just ca. 0.2% difference in omega-3 levels.”
• “Plasma phospholipid fatty acids as measured in this study are not a good index of long term intake and are influenced dramatically by a single meal, or even timing of a fish oil dose. A single fish oil dose massively increases LC omega 3 (typically increasing levels by 100% or more) in about 4-12 hours and then washes out around 48 hours.”
• “The study was not designed to look at omega-3 and confounded with selenium and Vitamin E used in the treatment arms.”
• “The test cohort included sick and healthy people. It is possible that sick people were taking fish oil supplements at a higher rate than the healthy individuals.”
• “A recent meta-analysis of fish consumption and prostate cancer by Szymanski et al. (2010) reported a large reduction in late stage or fatal prostate cancer among cohort studies." [7]
• "Several population based studies have shown a benefit of increased omega-3 fatty acid intakes to reducing prostate cancer risk.” [8]^, [9]

As I said earlier, this type of study raises questions about possible associations; but due to its built-in limitations, and results conflicting with most other related studies, provides no real answers.  Unfortunately, its counter-intuitive results generate sensational press coverage rarely accompanied by any true perspective on what this new study really means (not much).

In real life, most Americans and others in Western societies no longer consume the ideal amount or ratio of omega-3 fatty acids in their diet as our ancestors did a century or two ago. This reduction reportedly contributes to the large increase in chronic health problems that plague these societies. It is a public disservice to inappropriately scare people away from healthy foods and supplements, which help balance the diet in these many cases where the lack of essential nutrients is actually causing harm, based solely on such flimsy “evidence”. 

After reviewing this study I, a vegetarian, will continue to take my vegan DHA supplement twice a day with absolutely no concerns that it will negatively affect my own prostate health. Why am I not at all concerned? Because there is still no hard evidence explaining how long-chain omega-3 fatty acids like EPA and DHA may promote prostate cancer. There is still no demonstrated mode of action for this concern, and there are still no plausible explanations of any biological mechanisms that could justify the theory that long-chain omega-3 fatty acids may promote prostate cancer. My lack of concern is evidence based, after carefully reviewing the studies in question. Contrast this with the fear-mongering about fish, fish oil, and omega-3 fatty acids in foods and supplements that is overwhelmingly based on speculation, flimsy data, ignorance (on several levels), and maybe even some bias.

By Neil E. Levin, CCN, DANLA

REFERENCES:

[1] http://www.newswise.com/articles/view/605211/?sc=rssn&utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+NewswiseScinews+%28Newswise%3A+SciNews%29

[2] http://teacher.nsrl.rochester.edu/phy_labs/appendixe/appendixe.html

[3] http://www.hfma.co.uk/docs/Omega_3_and_Prostate_Risk-July2013.pdf

[4] The Preventable Causes of Death in the United States: Comparative Risk Assessment of Dietary, Lifestyle, and Metabolic Risk Factors" study, April 2009, PLoS Medicine

[5] http://www.crnusa.org/CRNPR13-Omega3071113.html

[6] http://us1.campaign-archive1.com/?u=4ae075406cd789efec4e9ff09&id=6f3dc7a018&e=1704ffc192

[7] Szymanski KM, Wheeler DC, Mucci LA. Fish consumption and prostate cancer risk: a review and meta-analysis. Am J Clin Nutr. 2010;92(5):1223–1233

[8] Terry P, Lichtenstein P, Feychting M, et al. Fatty fish consumption and risk or prostate cancer. Lancet, 2001,357:1764-6.

[9] Lietzman MF, Stampfer MJ, Michaud DS, et al. Dietary intake of n-3 and n-6 fatty acids and the risk of prostate cancer. Am J Clin Nutr 2004;80:204-216.

Does Fish Oil Dissolve Styrofoam - and Does That Prove It's Bad?

Recent attention given to the effects of various fish oils on polystyrene (Styrofoam®) cups has led to some misunderstanding of how these products work in terms of nutrition and safety. It is unfortunate that the use of these stunts imply may confuse or even scare people away from taking this natural product which provides constituents that are essential to human health. Don’t be fooled by this trick! If someone tries to use it as a means to push one product over another, challenge them to explain exactly what the test is supposed to mean. Here’s what you need to know about the test, how it works, and what it means:
Styrofoam® (polystyrene) cups can be dissolved by pure fish oils. All fish oils will have this same effect on polystyrene, but some will take much longer than others. Various healthy natural substances, like fresh lemon oil, will also dissolve polystyrene. In the Styrofoam® cup test, the esterified ethyl ester form of fish oil works to dissolve Styrofoam® much faster than the triglyceride form simply because the number of chemical bonds in the two forms of oil are different; with ethyl ester fish oil having its number of bonds closer to that of Styrofoam®. This similar chemical polarity is the same reason why pure lemon oil also works quickly to dissolve Styrofoam®. No solvents are used to produce the fish oils, so none are present in the finished products. This magic trick does not translate into any legitimate safety concerns, despite its obvious visual impact. Fortunately, the human body is not composed of polystyrene and is not negatively affected by fish oils in its commonly available forms.

Fish oil naturally comes in a volatile triglyceride (triacylglycerol) form and can be esterified for additional benefits. As soon as a fish is caught the oils begin to degrade and can easily go rancid. Esterification is a process that stabilizes and maintains the freshness of fish oil to prevent rancidity and allows higher concentrations of the essential omega-3 EPA and DHA fatty acids to be available. During this esterification process, the triglycerides are removed, changing the number of molecular bonds in the fish oil. Both the purified ethyl ester form and the triglyceride form must be digested to a simpler fraction, the free fatty acid, to allow bioavailability from the human gut. Ethyl ester and triglyceride forms are equally well digested by lipase and available for absorption as free fatty acids, and the ethyl ester form is at least as bioavailable as the triglyceride form. (1)

There is some evidence that the ethyl ester form will sustain circulating levels of the omega-3 fatty acids EPA and DHA better than the triglyceride form. The ethyl ester form of EPA and DHA is the form that is used in most successful clinical studies evaluating the potential health benefits of supplemental Omega-3 fats. In fact, clinical trials on the ethyl ester form more consistently generate positive results than those done with the triglyceride form. Also EPA and DHA as ethyl esters inhibit platelet aggregability and control serum triglycerides while leaving other serum lipids essentially unaltered. (2) The ethyl ester forms build up body stores, allowing conversion to free fatty acids more consistently than the triglyceride form. (3) Because of their proven benefits and safety, it would be unfortunate if a misunderstood “test” causes some people to reject the use of solvent-free ethyl ester fish oils as part of their diet.

Expert opinion:

http://www.biosyntrx.com/articles.php?id=690

http://www.newton.dep.anl.gov/askasci/chem03/chem03994.htm

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Technical explanation:

Chemical Polarity plays a role in how compounds react with one another. Polarity refers to the electro-magnetic charges of a molecule, or the attraction between the positively and negatively charged parts of a molecule. Compounds are considered polar due to the unequal sharing or electrons. For example, water is a polar compound. A compound is non-polar when the electric charge is balanced. Edible oils are typically non-polar.

In Chemistry there is a rule to describe how polar and non-polar solvents react with similar solutes: “like dissolves like”. We all know that oil and water do not mix. The reason why is that water, which is polar, will not react (mix) with oil, which is non-polar. “Like dissolves like.”

Two common compounds, sugar and salt, are both polar and in nature they readily mix with water, another polar compound.

With polarity, compounds of differing polarity do not react/mix, while those with like polarity do mix. So a chemical reaction occurs when a non-polar compound comes into contact with another non-polar compound, and more readily when the number of chemical bonds in one substance more closely matches the other.

Polystyrene, a moisture-resistant foam commonly known as Styrofoam®, is formed from a long chain of polymers. This plastic is used in the manufacture of coffee cups and plates as an insulator and as packaging material, and is non-polar. What makes Styrofoam® ideal for keeping most hot beverages hot and cold beverages cold is that as a non-polar compound it will not react with the polar water used to make coffee, tea, and other beverages. This same material will react with any form of edible oil; this can be olive oil, lemon oil, fish oil, etc. This reaction is naturally occurring and its intensity is based solely upon the chemical properties of both compounds and the polarity of each.

All edible oils, which like Styrofoam® are non-polar, are made up of fatty acids; and these fatty acids are made up of a long chain of hydrocarbon molecules. With Fish Oils, some contain triglycerides and some contain ethyl esters. Both the triglyceride form and the ethyl ester form first need to be digested and broken down to a free fatty acid for absorption from the GI tract. After uptake, the free fatty acid is then converted to a triglyceride form in the liver by the addition of already available triglycerides obtained from circulating lipids (fats).

In the example of fish oils, ALL will react with Styrofoam over time; the length of time is determined by the number of chemical bonds in each type of fish oil relevant to the number of chemical bonds in Styrofoam®. Triglycerides will take longer to react with the cup, while oils bonded to ethyl esters, which have more chemical bonds, will naturally penetrate the cup wall faster.

REFERENCES:

1. Krokan HE, Bjerve KS, Mørk E. The enteral bioavailability of eicosapentaenoic acid and docosahexaenoic acid is as good from ethyl esters as from glyceryl esters in spite of lower hydrolytic rates by pancreatic lipase in vitro. Biochim Biophys Acta. 1993 May 20;1168(1):59-67. PMID: 8504143
2. von Schacky C. A review of omega-3 ethyl esters for cardiovascular prevention and treatment of increased blood triglyceride levels. Vasc Health Risk Manag. 2006;2(3):251-62. Review. PMID: 17326331
3. Rupp H, et al. Risk stratification by the "EPA+DHA level" and the "EPA/AA ratio" focus on anti-inflammatory and antiarrhythmogenic effects of long-chain omega-3 fatty acids. Herz. 2004 Nov;29(7):673-85. Review. Erratum in: Herz. 2004 Dec;29(8):805. PMID: 15580322

Fish Oil: Excerpts from a magazine interview with me

The balance of fatty acids in the body can promote inflammatory or non-inflammatory states. Higher amounts of omega-3 fats in the diet have been shown to modulate inflammation and keep it within healthy ranges. The various cellular and tissue damage that can occur from chronic inflammatory states are certainly not healthful. This basic mechanism of action implies a wide-ranging and powerful effect of omega-3 fats to support wellness. Additionally, these fats are part of brain and nerve structures, so they help to maintain the health of those tissues, as well.

Omega-3 and omega-6 fats have been called “essential fatty acids” since the body can’t manufacture them from other fats, as it typically can for other types of fat. The optimal ratio of omega-6 to omega-3 fats is somewhere between 1:1 and 3:1. The common American diet has been estimated to be over 15:1, a marked deviation from a healthy norm.

The benefits of most other non-omega-3 fatty acids in fish oil are not well-defined in the scientific literature. Fish oil naturally contains a range of fats, including cholesterol, triglycerides, and stearic acid. The ones that are considered less desirable, cholesterol and triglycerides, are sometimes removed from fish oils to further concentrate the omega-3 portion and allow higher strengths in fewer capsules.

All natural oils contain various mixtures of fatty acids in varying amounts. Omega-9 fats are best known as being abundant in Olive Oil, and are considered non-inflammatory and especially healthy if substituted for most omega-6 fats that are pro-inflammatory. Some natural oils are fairly well balanced, such as flax and hemp seed oils, or walnut oil. Others, like fish oil, tend to be predominantly omega-3. Most vegetable oils are mostly omega-6 fats and their predominance in the modern diet has been blamed for some of our poor health.

Some consumers do know about various sources of fish oil, and some have advantages or disadvantages. For example salmon is a favored source of omega-3 fats, though salmon oil typically contains less than other common fish oils. Traditional fish sources may be better accepted by those who won’t or can’t eat shellfish. The fisheries in Norway and Peru are among the best managed traditional fisheries on earth.

Krill, a small crustacean shellfish, is a unique source of omega-3 fats since krill also naturally bonds the fatty acids to phospholipids, which are essential for cell membranes and which enhance the bioavailability of the oil. Krill oil also contains the powerful antioxidant pigment astaxanthin, which is responsible for the color of shrimp and salmon. Krill is considered the best managed fishery in the world, with trained observers on each boat monitoring the harvest. The krill harvest limit can be rapidly adjusted to support a healthy population, and the total world harvest (most of which goes into pet foods) is only a fraction of the allowable sustainable harvest level.

Essential fatty Acids (EFAs) interview, Natural Products Marketplace magazine, January, 2011

The awareness of EFAs, especially the Omega-3 fatty acids EPA and DHA, is large and growing larger. The accumulating mountain of evidence and the endorsement by popular health “gurus” assures continued growth in this important product category. As the benefits of specific fatty acids for regulation of various healthy body functions – such as inflammatory processes, hormonal health, and maintaining brain/nerve/cellular structures – becomes even more well known, more and more people recognize the potential for EFAs to positively affect their health.

While there are combination products that deliver Omega-3, Omega-6, and Omega-9 fatty acids together, the focus has been more on specific sources such as fish or flax, along with some more unusual ones. Of course, natural oil sources are not comprised of a single fatty acid. For example, natural fish oil can not only supply EPA and DHA but also originally supplies ALA, cholesterol, triglycerides, and other fatty acids; though many of these components can be removed during processing to provide purer and stronger materials that are richer in EPA and DHA to require far fewer capsules to reach desired levels of these two fractions. Flax oil is best known as a vegetarian source of the omega-3 fatty acid ALA (alpha-linolenic acid), but ALA levels are only about 55% of the total; flax oil also contains about 19% omega-9 as oleic acid, 14% omega-6 as linoleic acid, and 12% saturated fats. The conversion of ALA to EPA is a significant metabolic hurdle. Women do this conversion better than men; people who consume the most omega-6 in their diets have a more difficult time converting ALA to EPA. Typically between 5% and 15% of ALA converts to EPA and about 2% to 5% of ALA converts to DHA, making flax a much more dilute and less certain source of EPA-DHA.

Fish oil is subject to environmental concerns related to both sustainability and contaminants. Manufacturers audit their suppliers and set strict identity/safety specifications to assure the quality of products.

Most fish oils are molecularly distilled to remove contaminants, manufactured under strict quality assurance standards, and screened to be free of potentially harmful levels of contaminants and heavy metals, such as mercury, PCB’s, dioxins, and others.

Other types of EFAs include Flax seed oil, Evening Primrose Oil, Pumpkin seed oil, Black Currant seed oil, Wheat Germ oil, Castor Oil, and Virgin Coconut Oil.

Purity, potency, and freshness are always the challenges with EFAs.

The trend is toward more concentrated products of higher purity that allow people to get their EPA and DHA with smaller quantities of capsules or less volume of liquid. Liquids and smaller capsule sizes allow more children and seniors to enjoy the benefits of fish oils, while high strength capsules better hit the main demographic in between.

All fish oil supplements are typically hundreds of times safer than eating a serving of fish in relation to environmental factors; and typical esterified products have the added benefit of being free of cholesterol and triglycerides, which are undesirable food components for those with high cholesterol. By far, most of the studies proving the health benefits of supplemental fish oils have been with the esterified (ethyl ester) form, rather than the triglyceride form found in cold water fatty fish. There is very strong science supporting the use of this form.

Esterified fish oils also have been shown to sustain human serum levels better than the triglyceride form, over both a 24-hour period and a one-month period, which better supports a healthy heart rhythm. Notably, the most concentrated products are available only as esterified fatty acids. The ability of a consumer to get the 1-3 grams daily of EPA + DHA recommended by many health experts is enhanced by modern formulas that concentrate these essential fatty acids into fewer capsules and smaller serving sizes with fewer undesirable components, thus increasing customer compliance with a healthy nutritional protocol.

Both triglyceride and esterified ethyl ester fish oils are available in the marketplace, and both forms have their advocates. In the body, both forms must first be digested, stripping off the triglycerides or ethyl esters and leaving only free fatty acids that can be readily absorbed. These free fatty acids are then combined with triglycerides present in the liver before entering general circulation; so the circulating form will actually be the triglyceride form, no matter which form of fish oil one consumes. Both forms provide great value and important nutrients for the consumer; but the triglyceride form has no more proven value than the ethyl ester form, despite some excessive marketing claims.

In Defense of Natural Foods: Fish Oils

In Defense of Natural Foods

By Neil E. Levin, CCN, DANLA

A public debate is now raging over the safety of natural fish oils. In truth, though, this should be more properly recognized as a narrowly focused legal debate rather than representing any real question as to whether these natural food products are good for us to eat; because health authorities around the world have already acknowledged that it is generally better to eat natural fish and fish oils than to avoid them. Yet a quirk in California law makes it possible for some environmental lawyers to argue that the general scientific and medical consensus on the known health benefits of natural fish products be ignored; instead touting zero tolerance for pollutants that are widespread in our food supply and advocating that only highly processed oils be sold.

I am certainly not in favor of pollutants; my bona fides are clear. As a student I led environmental classes in my school on the first Earth Day on April 22, 1970 and have broken whole grain bread with the late Earth Day founder Senator Gaylord Nelson at a natural food Thanksgiving dinner. I spent a day with Al Gore at a solar symposium that he hosted in Tennessee in the late 1970’s. My wife and I live on a 4-acre wooded hillside that is a National Wildlife Federation Certified Wildlife Habitat™. We have recycled, grown and bought organic food, used primarily natural and biodegradable products in our home, politically and financially supported several environmental groups, and otherwise have been ardent environmentalists for some 40 years. I’ve worked in the natural food industry for my entire adult life and am so into it that I became a clinical nutritionist who reads complex nutrition studies for kicks. So when I question other environmentalists for creating a public panic that may turn people off from eating foods that provide scientifically demonstrated health benefits despite the possibility of tiny amounts of pollutants being in them, it may merit some attention.

The attorneys argue that only highly processed fish oils are acceptable; all other fish oil products should have label warnings that they may contain parts-per-billion (ppb) amounts of PCBs, a banned industrial chemical that is still so widespread in the environment that the native people of the far north have it in their bodies from the wild fish that is the base of their traditional diet.

According to the Food and Drug Administration (FDA), “Small amounts of PCBs can be found in almost all outdoor and indoor air, soil, sediments, surface water, and animals. However, PCB levels have generally decreased since PCB production stopped in 1977. People are exposed to PCBs primarily from contaminated food and breathing contaminated air. The major dietary sources of PCBs are fish (especially sportfish that were caught in contaminated lakes or rivers), meat, and dairy products.”

What are the health impacts of PCBs? That is really hard to say. Most negative reports are from rodent studies, where the animals are fed huge amounts for long periods. The FDA reports that, “PCBs are not known to cause birth defects,” and has no cases on record, so that concern seems unfounded, despite the claims of the current private lawsuit. The agency does report that PCBs are probable carcinogens based on such animal studies and cases of industrial workers exposed to substantial amounts of the chemicals. It also reports developmental problems in children of mothers exposed to “high” amounts, but not specifically birth defects and not at significantly harmful levels. “Some studies have estimated that an infant who is breast fed for 6 months may accumulate in this period 6–12% of the total PCBs that will accumulate during its lifetime. However, in most cases, the benefits of breast-feeding outweigh any risks from exposure to PCBs in mother’s milk.”

Fortunately, the FDA has also estimated that the amount of PCBs in food is steadily declining since the chemicals were banned. Between 1978 and 1991, the estimated daily intake of PCBs in adults from dietary sources declined by about 62%. “Meat and dairy products are other important sources of PCBs in food, with PCB levels in meat and dairy products usually ranging from less than 1 part in a billion parts (ppb) of food to a few ppb.” That means a Quarter Pound burger weighing about 113 grams could lawfully contain hundreds of nanograms (billionths of a gram, or parts-per-billion) of PCBs, approaching about half a microgram (a microgram is one-millionth of a gram, or one part-per-million). If you got somewhat less from a natural fish oil, plus enjoyed the added cardiovascular benefits of the essential Omega-3 fatty acids it provides versus the known cardiovascular risks of beef and other animal fats, should that really be a great concern, especially when heart disease is blamed for about half the deaths in this country?

The official Health Canada federal agency reports that, “Exposure to these low levels does not appear to affect human health. Based on recent results from Total Diet Studies (a series of studies organized by Health Canada), the average daily dietary intake of PCBs is thought to be less than half of one microgram (one microgram = one-millionth of a gram). People who eat large amounts of sports fish, wildlife or marine mammals may be exposed to higher dietary levels of PCBs…Media reports have raised concerns about PCBs in farmed salmon. Health Canada and the Canadian Food Inspection Agency recently completed a survey of farmed and wild fish. The survey analyzed a large number of samples for PCBs. The results showed that eating salmon from the commercial food supply (whether farmed or wild) does not pose a health risk to consumers.”

The UK Food Standards Agency has reported that the health benefits of eating moderate amounts of fish, including salmon, as part of a healthy balanced diet outweighed any potential risk from PCBs. Based on 21 surveys carried out by the Agency results found that exposure to these contaminants from the diet has fallen by about 75% between 1982 and 1997.

How has the U.S. federal government determined safe levels of PCBs in foods? “The FDA has set residue limits for PCBs in various foods to protect from harmful health effects. FDA required limits include 0.2 parts of PCBs per million parts (ppm) in infant and junior foods, 0.3 ppm in eggs, 1.5 ppm in milk and other dairy products (fat basis), 2 ppm in fish and shellfish (edible portions), and 3 ppm in poultry and red meat (fat basis).” Two ppm in fish is equivalent to 2,000 ppb (parts-per-billion) in fish. The fish oil products in question today contain less as a percentage by weight than is allowed even in baby food, and are taken in far smaller amounts by total weight per serving than whole fish. Yet these fish oils are now being targeted for added label warnings that they are known by the state of California to contain toxins with the false implication that these minute dietary amounts are proved to be harmful and should be avoided at all costs.

What are the alternatives? Apparently eating actual fish won’t do; they would be consumed at far larger serving weights and naturally contain far more PCBs than a serving of natural fish oil. Yes, some fish oils are highly purified, which is what the lawyers argue as a reasonable alternative to the natural oils. Yet there are legitimate critics who argue against chemically processing and refining natural food products such as this, even for reasons of purity. And some of the oils most likely to have accumulated PCBs are from long-lived fish which are higher in the ocean food chain and have been long valued as health foods with strong evidence of enhancing human health, like cod liver and salmon oils.

If we force all foods to either have disproportionally scary warnings or be processed out of their natural states, pushing only the least natural products as the “best” choices, this has serious implications for the nature of our food supply and how it impacts our nutritional status. We have seen degenerative disease rates soar as the amount of refined foods in the diet increases, and natural food advocates have long argued that we return to unrefined whole foods in order to naturally maintain health. This current fish oil scare is capable of needlessly frightening people away from taking safe healthy fish oils that could improve their health. That would be the real crime.

References:

Agency for Toxic Substances and Disease Registry (ATSDR). 2000. Toxicological profile for Polychlorinated Biphenyls (PCBs). Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service. http://www.atsdr.cdc.gov/toxprofiles/phs17.html

Health Canada http://www.enotalone.com/article/10328.html

The UK Food Standards Agency

Mislabeled Vegan Supplements?

It appears that some vitamin brands are listing their products as Vegan, yet formulating them with vitamin D3 synthesized from Sheep's Lanolin. There is no Vegan source of vitamin D3, which is produced by chemical synthesis when animal fats called sterols are exposed to Ultraviolet light (UVB rays). D3, or cholecalciferol, is always made from animal fat. The other form, vitamin D2, or ergocalciferol, is from a Vegan source; though one has to watch out for animal gelatin stabilizers and microbeads in microencapsulated dry forms, especially. Vegan microencapsulation for dry forms of fat-soluble nutrients including beta-carotene and lutein was only perfected in mid-2005, so it is possible that some products made before then were mislabeled as Vegetarian if the company did not investigate its raw material sources carefully. (Many brands do not manufacture their own vitamin supplements, relying on contract manufacturers to make their outsourced formulas for them. In many cases, the brands do not normally have access to the full ingredient and finished product specifications of the actual manufacturer. This can lead to ignorance and errors when making label claims related to the presence or absence of allergens and animal products.) The D2 form is synthesized from plant sterols exposed to the same kind of light. Plant sterols, by the way, have an FDA-approved health claim that they "may reduce the risk of heart disease" and are considered healthy. http://www.fda.gov/Food/GuidanceComplianceRegulatoryInformation/GuidanceDocuments/FoodLabelingNutrition/FoodLabelingGuide/ucm064919.htm There is also a controversy over whether D3 is much better than D2. D3 is the form found in fish liver oils and is often added to fortify foods such as milk and orange juice. D3 is also the form that we synthesize in our own bodies when cholesterol (that animal sterol aforementioned) is exposed to UVB rays. D2 is likewise made by plants when their oils (plant sterols, or phytosterols) are exposed to UVB light. In modern studies, both forms are equally well absorbed and both are good at preventing rickets and maintaining bone mass. Both forms equally maintain the level of the active compound serum 25(OH)D3 levels. "Therefore, vitamin D2 is equally as effective as vitamin D3 in maintaining 25-hydroxyvitamin D status." http://www.sciencedaily.com/releases/2008/01/080102122306.htm It appears that D3 tests better than D2 in an occasional dosing schedule, like if you got it once a month from a doctor's office. But the assay is apparently flawed and is now known to not measure D2 very well, underestimating its circulating level. For everyday supplementation and fortification, both forms work equally well by all current measures. Some brands with "cultured" or "fermented" ingredients apparently believe that adding lanolin-sourced vitamin D3 to a yeast culture, then drying the whole thing and using it to make vitamins, somehow transmutes the animal fat form of the vitamin into a Vegan-friendly ingredient. They say that the yeast consumes the lanolin-derived vitamin and that the yeast is Vegan no matter what it is fed. But they present no evidence that yeast consumes vitamin D or changes it in any way. Quite the contrary; they brag about providing vitamin D3 – a known animal product - in a supposedly Vegan supplement. This indicates that they know that the form is not changed in any significant way by the yeast culture. One major brand, when asked by me only today, said that they do not disclose their D3 source for their vitamin labeled as Vegan because the source is both "irrelevant" and "proprietary". In other words, they won't tell us and we don't need to know. That pisses me off, pardon me for taking this apparent contempt for Vegans personally. I am not a Vegan but have been a vegetarian since 1972. I do not eat any type of flesh; avoiding not only all forms of meat but also animal broths, gelatin and leather. I scrutinize labels to assure that I am getting no animal products except for dairy, eggs, and honey. Now the Honest Nutritionist in me wants to sound the alarm that some companies are using animal products like gelatin and lanolin in their Vegan-claimed dietary supplements. Whether it's an honest (though sloppy) mistake or a deliberate attempt to have their cake and eat it too is hard to say for sure, but either way this is not fair to Vegans. I tend to fear the worst since they claim the supposedly superior and more popular D3 form in a product whose label also appeals to Vegans and Vegetarians who are being led to erroneously believe that there is now a Vegan-friendly source of D3. There isn't. It is just not true. We are being misled. D3 is not Vegan. D2 is, and is not a bad form as some try to claim. Some medical experts even want to routinely fortify the food supply with D3 because of the largely mythical superiority of that form; that would deprive all Vegetarians and Vegans of their right to avoid hidden animal products in our food. I believe that we have a fundamental right to select our diets based on individual religious, ethical, and cultural beliefs. It is wrong for a corporation to take that right away from us by incorrectly labeling their products that are marketed to Vegetarians and marked as Vegan. Mislabeled products are considered to be adulterated. Obviously, there is no safety issue here and it does not seem as if this matter has attracted much attention, as of yet. But these jokers have attracted my attention and I think that they deserve to get grassroots attention to their attempt to sell non-Vegetarian products to Vegetarians and Vegans. I am not naming names here but will not buy products made by any companies which suggest that animal-source D3 can ethically be sold to Vegans. If you are of the Vegetarian or Vegan persuasion, please check your product labels. If I see vitamin D3 in a product labeled as Vegetarian, I’d feel free to return it to the store as a mislabeled product and get my money back. Vote with your dollars and read product labels carefully before buying anything. If enough people do this, the companies with questionable products will have to deal with a lot of returns from unhappy customers and stores, combined with a drop in sales. Eventually, they will be forced to either correct their labels or change their formulas.

Advice on Diet for Cancer Survivors

• avoid all animal proteins, they trigger cancer cell activity (esp. the milk protein: casein)
• organic diet
• plant based diet
• no microwaving, esp. in plastics!!!
• fish oil (molecularly distilled)
• mixed carotenoids (vs. beta-carotene) from food or supplements
• medicinal mushrooms (the common white button and portabella mushrooms will not hurt but won't help)
• low temp saunas for detoxification

Memory and Age

Memory and Age By Neil E. Levin, CCN, DANLA The most important things for an older person to consider in protecting against minor memory loss – often attributed to “aging” – include: · Maintain at least a nominal physical activity level to keep circulation and body functions at optimal levels. · Take a good multivitamin to assure minimal levels of essential nutrients. Too many elders fail to eat properly or to get adequate levels of B vitamins and other key nutrients associated with proper cognitive function. Also, the elderly don’t absorb nutrients from food as efficiently, making supplementation even more important. · Don’t forget to eat meals. Often, single, divorced or widowed seniors fail to eat regular meals on schedule. This creates nutrient deficiencies that complicate their ability to maintain physical and mental health. · Don’t overeat on processed, high fat, high sodium foods such as fast foods to “compensate” for poor eating habits. · Take foods and supplements that are rich in antioxidants. Oxidative damage is clearly associated with many of the conditions that affect mental, as well as physical, capabilities in older people. This includes negative changes to the brain itself; and also the nervous system, the eyes and joints. · Use vitamin D, which may be in your multivitamin or calcium supplement, to compensate for the lack of direct sunlight on skin. This essential vitamin also helps with immunity, cardiovascular health and bone health. · If your dietary habits are reasonably good and you still want some more natural aids for brain and memory function, consider a brain nutrient formula. Of course, college age is a time when many students want to use brain nutrients to maximize their learning and recall, especially for tests. Many adults then coast through adulthood until they reach their 40’s or 50’s and start to get a little forgetful. By then, they should already be examining their diet, lifestyle and stress levels to consider whether they may need additional nutritional support for their mental functions. If they wait until things get bad - in their 60’s, 70’s or later - it may be too late to preserve their memories and mental acuity. Basic brain nutrients are multivitamins, lecithin and fish oil. Antioxidants will protect the brain’s structures and functions throughout adulthood. Magnesium, an essential mineral that is deficient in 90% of Americans, helps to reduce toxic effects of chemicals on neurons; as do antioxidants such as vitamin E, tocotrienols, and vitamin C. People will usually hint at the need, or ask about Ginkgo or look at the section. We’re not the family, friends or work colleagues that people try to hide symptoms from…after all; we are the ones that perfect strangers often disclose their bowel habits and other normally hidden quirks to. Speaking in user-friendly but technical structure-function language will often make the discussion less personal and more scientific, removing much of the emotional content of the health issue. Phosphatidyl Serine is a phospolipid compound derived from soy lecithin that plays an essential role in cell membrane composition and intercellular communication. Phosphatidyl Serine is a major structural component of neural membranes where it assists in the conduction of electrical impulses and facilitates the activity of neurotransmitters involved in learning, memory and mood. These properties make Phosphatidyl Serine formulas ideal basic supplements for the support of cognitive function. There is enough evidence of the safety and efficacy of PS for the FDA to have issued a qualified health claim for it. DMAE is known primarily as a precursor to choline and acetylcholine (chemicals in the brain responsible for nerve transmissions and cognitive function), and has been used most predominantly to improve memory and focus while stimulating neural activity. Many researchers believe that it may serve an anti-aging function by increasing the body’s capacity to produce acetylcholine – a deficiency commonly associated with memory loss. Scientific research has demonstrated that Ginkgo Biloba Extract has antioxidant activity in in vitro studies and thus may aid in maintaining healthy brain and memory function. The insulating myelin sheaths that protect the brain, spine and thousands of miles of nerves in the human body are almost two-thirds Lecithin. Lecithin is composed of many different components, including Choline, Inositol, Linoleic Acid, Phosphatidyl serine, fatty acids and triglycerides. These valuable constituents of Lecithin are vital for the proper functioning of many metabolic processes. And let’s not forget the benefit of DHA and fish oil. Fish oils are typically molecularly distilled and tested to be free of screened for the absence of potentially harmful levels of contaminants (i.e. mercury, heavy metals, PCB's, dioxins, and other contaminants). DHA is utilized in forming the brain and nerves. And last but not least, antioxidants and magnesium are very helpful in protecting brain structures and may be useful in preventing some of the feared declines associated with aging brains. For example, vitamin C actually pumps glutamates out of neurons.

Nutrients for Joint Health

Nutrients for Joint Health By Neil E. Levin, CCN, DANLA Most people know that glucosamine sulfate and chondroitin sulfate are important components of joint health. They help to form spongy tissues (like articular cartilage) that hold moisture and cushion the body’s joints, protecting them from excessive wear and tear. But this takes time. Some people notice a change in joint function within days, but more typically over several weeks. Studies show that these substances help to maintain distances between joint structures over many months, a key measure of joint integrity as these structural components may slowly collapse if not nourished. This particular effect has been accepted as evidence-based by conventional physicians at a medical joint health center associated with a major university hospital. People with osteoarthritis typically may have low levels of glucosamine and chondroitin sulfates, as well as MSM, and may benefit by supplementing to restore normal levels of these soft tissue nutrients. MSM is a safe form of the mineral sulfur that may preserve joint function and structures. In order to affect joint health on a short-term basis, it may be useful to supplement the diet with herbs that inhibit the activity of the enzymes that are involved in normal inflammatory processes. These herbs may mediate COX-2 or 5-LOX enzymes. COX-2 is also the target of some widely used drugs. Some of these herbs are safe, common spices like turmeric, ginger, cayenne and the enzyme bromelain. While drugs may offer similar yet faster COX-2 inhibition, herbs can also modulate 5-LOX activity. The safety profiles and beneficial side effects associated with nutrients and herbs can be preferable to the known side effects of drugs. The antioxidant components in the herbs also improve the body's ability to repair tissues by stimulating collagen formation. A diet high in animal fat is implicated in joint problems, and experts frequently recommend that sufferers reduce their intake of most animal fats. It is important to take natural healthy essential fats, especially Omega-3 fats (cold water fatty fish, fish oil, flax seeds, flax oil) and Omega-6 fats CLA and GLA from vegetable oils. All fish oils are well-filtered and/or molecularly distilled to remove environmental contaminants and heavy metals. A low-fat, gluten-free vegetarian diet has been helpful if maintained for several months, but does not produce fast results and is best combined with other approaches, such as supplementation. Wheat and milk are often implicated in immune reactions, and it is sometimes best to avoid them, at least while addressing the problems. Joint problems have also been linked to leaky gut and maldigestion of food, leading to the body’s immune cells attacking undigested proteins. This trains immune cells to recognize food proteins as invasive organisms and respond to them aggressively, leading to food sensitivities that are not classic allergies. Since some undigested or partially digested proteins may be similar to body tissues, maldigestion could partially explain why the body sometimes attacks its own tissues. If so, there are aids to proper digestion that should be considered. Good digestion is a tool to prevent immune reactions to food and the human gut should serve as an immune barrier to pathogens in food. Take time to smell and think about your food before you eat. Avoid stress or distractions during meals. Carefully chew food to a liquid before swallowing, and even chew liquids to enhance contact with digestive enzymes in saliva. If necessary, take a high quality plant enzyme or a milk-digestive enzyme. In some cases, more stomach acid is needed to digest proteins (and minerals). HCl and Pepsin supplements do this, but sometimes much larger amounts of acid than normal are recommended by health professionals (600-2400 mg), which do have risks if you don’t need that much acid, so these high doses must be taken under medical supervision. A traditional home test to determine whether more acid would help digestion is to mix a tablespoon of (preferably raw and organic) apple cider vinegar into a glass of (pure) water and drink with a meal. If it helps digestion, you may need more acid. It may not noticeably help if you require very much acid, though. A tablespoon of raw honey can also be added to this beverage to enhance digestion, also making it taste more like apple juice. If it helps, this can be taken daily with meals. Some digestive enzymes like Bromelain and Serrazimes (serratopeptidase) can be taken between meals to help control substances associated with temporary joint discomfort. A protective layer of probiotics - acidophilus, bifidus and other “friendly bacteria” - actually lines healthy GI tracts like chain mail, preventing leakage of undigested food remnants from the gut that provoke immune responses. It is wise to supplement with healthy bacterial supplements such probiotic products. Fairly high doses of Vitamin E have been shown to help maintain joint health, but I recommend taking the full Vitamin E Complex containing eight forms of natural Vitamin E compounds, not just the alpha tocopherol. Other antioxidants are important to maintain joint health. These include the minerals selenium and zinc, vitamins A, C, E and many plant compounds. GliSODin® raises body levels of key antioxidant enzymes, such as SOD and glutathione. Celadrin® products may help to maintain joint mobility, taken orally or topically applied, and contain acetylated fatty acids from beef fat. MicroLactin™ is a milk protein fraction that helps prevent certain immune cells (cytokines) from overwhelming an area and maintaining a prolonged reaction. Time and patience may be required to find a program that works for any individual’s joint health. Many supplements work best over weeks, months or years. Stretching and gentle exercise often help people, so should be part of any comprehensive program. Yoga and Tai Chi, and variants such as water Ai Chi, are low-impact activities that aid posture and build muscle strength. Glucosamine, Chondroitin and MSM (methylsulphonylmethane, an organic form of sulfur found in all living organisms) are three of the most popular and effective nutrients for supporting joint health. There are other formulations of Glucosamine, including a vegetarian version from fungal fermentation. Studies have shown that these nutrients provide dietary components that support healthy joint structure and function. Look for substances, forms and potencies successfully used in clinical studies. REFERENCES: Chan PS, Caron JP, Orth MW. Effect of glucosamine and chondroitin sulfate on regulation of gene expression of proteolytic enzymes and their inhibitors in interleukin-1-challenged bovine articular cartilage explants. Am J Vet Res. 2005 Nov;66(11):1870-6. Chan PS, Caron JP, Rosa GJ, Orth MW. Glucosamine and chondroitin sulfate regulate gene expression and synthesis of nitric oxide and prostaglandin E(2) in articular cartilage explants. Osteoarthritis Cartilage. 2005 May;13(5):387-94. Deal CL, Moskowitz RW. Nutraceuticals as therapeutic agents in osteoarthritis. The role of glucosamine, chondroitin sulfate, and collagen hydrolysate. Rheum Dis Clin North Am. 1999 May;25(2):379-95. Kelly GS. The role of glucosamine sulfate and chondroitin sulfates in the treatment of degenerative joint disease. Altern Med Rev. 1998 Feb;3(1):27-39. Bijlsma JW. [Glucosamine and chondroitin sulfate as a possible treatment for osteoarthritis] Ned Tijdschr Geneeskd. 2002 Sep 28;146(39):1819-23. Ameye LG, Chee WS. Osteoarthritis and nutrition. From nutraceuticals to functional foods: a systematic review of the scientific evidence. Arthritis Res Ther. 2006;8(4):R127. Kim LS, Axelrod LJ, Howard P, Buratovich N, Waters RF. Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial. Osteoarthritis Cartilage. 2006 Mar;14(3):286-94. Ebisuzaki K. Aspirin and methylsulfonylmethane (MSM): a search for common mechanisms, with implications for cancer prevention. Anticancer Res. 2003 Jan-Feb;23(1A):453-8. Parcell S. Sulfur in human nutrition and applications in medicine. Altern Med Rev. 2002 Feb;7(1):22-44. Bruyere O, Pavelka K, Rovati LC,et al. Glucosamine sulfate reduces osteoarthritis progression in postmenopausal women with knee osteoarthritis: evidence from two 3-year studies. Menopause. 2004 Mar-Apr;11(2):138-43.