Prebiotics

Overview

Fructo-oligosaccharides (FOS) also called “prebiotics” are a group of non-digestible compounds that stimulate the growth of beneficial microflora (note: this is different than PRO-biotics, or the actual beneficial bacteria such as acidophilus and bifidum). In terms of chemistry, a fructo-oligosaccharide (FOS) is a glucose molecule bonded to multiple fructose molecules. These bonds cannot be broken down by enzymes in the human small intestine - allowing the FOS to reach the large intestine intact, where it becomes a substrate for colonic bacteria. The effects of short-chain FOS have been studied for nearly two decades. Groups of oligosaccharides can be found in foods such as beans, blueberries, and onions; a liquid supplement is available in Japan, and FOS is available in capsule form in the U.S.

Comments

Prebiotics have been shown to selectively stimulate the growth and activity of benefical bacteria in the colon. The prebiotic, fructooligosaccharide (FOS), is found naturally in many foods, such as wheat, onions, bananas, honey, garlic, and leeks – and FOS can also be isolated from chicory root or synthesized enzymatically from sucrose (both more commonly found in FOS dietary supplements). Fermentation of FOS in the colon results in a large number of physiologic effects including increasing the numbers of bifidobacteria in the colon, increasing calcium absorption, increasing fecal weight, shortening of gastrointestinal transit time, and possibly lowering blood lipid levels.

Based on the available scientific evidence, FOS supplements are generally claimed to boost levels and activity of beneficial gut bacteria and thus promote general gut health, reduce serum lipids, increase intestinal calcium absorption, alleviate antibiotic-induced diarrhea, and reduce both the severity of irritable bowel syndromes and the risk of colon cancer.

Scientific Support

Short-chain FOS is metabolized in the colon (by colonic bacteria) into short-chain fatty acids (Giacco et al. 2004). These short-chain fatty acids cause a drop in pH, which may inhibit the growth of pathogenic bacteria, facilitate intestinal calcium absorption, and act as an energy substrate for colonic epithelial cells (Bouhnik et al. 1999, Tahiri et al. 2001). By manipulating colonic pH and microflora content, FOS may also play a protective role against colon cancer (Giacco et al. 2004, Swanson et al. 2002, Ten Bruggencate et al. 2003 and 2004). Research also points to a reduction in liver fatty acid synthesis as a possible mechanism for serum lipid reduction (Giacco et al. 2004, Swanson et al. 2002).

Human studies have shown significant increases in bifidobacteria (beneficial bacteria in the gut) from ingestion of as little as 6-8 grams of short-chain FOS per day (Chow 2002). Research has also shown decreases in pathogenic colonic bacteria from FOS ingestion (Chow 2002). There is evidence that short-chain FOS can lower cholesterol and triglycerides, but most of this research has involved animal models. Colon tumors and indicators of cancer have also been reduced in animal models. Although animal studies have given promising results, relatively few human studies have shown that mineral absorption can be enhanced from FOS ingestion (Tahiri et al. 2001).

Safety/Dosage

Since the bonds of FOS are not digestible, bacterial metabolism in the large intestine produces gas and bloating. Flatulence is a common symptom associated with FOS ingestion and can be worse in people who are lactose intolerant (depending on how the FOS is processed). Studies have shown that the severity of symptoms is dose-dependent (less FOS = less symptoms). Ingestion of 20-30 grams per day has been associated with the onset of severe discomfort – but symptoms may be alleviated by starting with a small dose and increasing gradually to the desired amount (Bouhnik et al. 1999). Ten grams of FOS per day appears to be the “optimal” dose, since this amount produces a significant increase in bifidobacteria and is fairly well-tolerated.

References

1.Alles MS, Hautvast JG, Nagengast FM, Hartemink R, Van Laere KM, Jansen JB. Fate of fructo-oligosaccharides in the human intestine. Br J Nutr. 1996 Aug;76(2):211-21.

2.Bouhnik Y, Flourie B, Riottot M, Bisetti N, Gailing MF, Guibert A, Bornet F, Rambaud JC. Effects of fructo-oligosaccharides ingestion on fecal bifidobacteria and selected metabolic indexes of colon carcinogenesis in healthy humans. Nutr Cancer. 1996;26(1):21-9.

3.Bouhnik Y, Vahedi K, Achour L, Attar A, Salfati J, Pochart P, Marteau P, Flourie B, Bornet F, Rambaud JC. Short-chain fructo-oligosaccharide administration dose-dependently increases fecal bifidobacteria in healthy humans. J Nutr. 1999 Jan;129(1):113-6.

4.Chow J. Probiotics and prebiotics: A brief overview. J Ren Nutr. 2002 Apr;12(2):76-86.

5.Djouzi Z, Andrieux C. Compared effects of three oligosaccharides on metabolism of intestinal microflora in rats inoculated with a human faecal flora. Br J Nutr. 1997 Aug;78(2):313-24.

6.Flickinger EA, Hatch TF, Wofford RC, Grieshop CM, Murray SM, Fahey GC Jr. In vitro fermentation properties of selected fructooligosaccharide-containing vegetables and in vivo colonic microbial populations are affected by the diets of healthy human infants. J Nutr. 2002 Aug;132(8):2188-94.

7.Giacco R, Clemente G, Luongo D, Lasorella G, Fiume I, Brouns F, Bornet F, Patti L, Cipriano P, Rivellese AA, Riccardi G. Effects of short-chain fructo-oligosaccharides on glucose and lipid metabolism in mild hypercholesterolaemic individuals. Clin Nutr. 2004 Jun;23(3):331-40.

8.Gibson GR. Dietary modulation of the human gut microflora using prebiotics. Br J Nutr. 1998 Oct;80(4):S209-12.

9.Luo J, Van Yperselle M, Rizkalla SW, Rossi F, Bornet FR, Slama G. Chronic consumption of short-chain fructooligosaccharides does not affect basal hepatic glucose production or insulin resistance in type 2 diabetics. J Nutr. 2000 Jun;130(6):1572-7.

10.Moore N, Chao C, Yang LP, Storm H, Oliva-Hemker M, Saavedra JM. Effects of fructo-oligosaccharide-supplemented infant cereal: a double-blind, randomized trial. Br J Nutr. 2003 Sep;90(3):581-7.

11.Piche T, des Varannes SB, Sacher-Huvelin S, Holst JJ, Cuber JC, Galmiche JP. Colonic fermentation influences lower esophageal sphincter function in gastroesophageal reflux disease. Gastroenterology. 2003 Apr;124(4):894-902.

12.Rao AV. Dose-response effects of inulin and oligofructose on intestinal bifidogenesis effects. J Nutr. 1999 Jul;129(7 Suppl):1442S-5S.

13.Roberfroid M. Dietary fiber, inulin, and oligofructose: a review comparing their physiological effects. Crit Rev Food Sci Nutr. 1993;33(2):103-48.

14.Roberfroid MB, Van Loo JA, Gibson GR. The bifidogenic nature of chicory inulin and its hydrolysis products. J Nutr. 1998 Jan;128(1):11-9.

15.Roberfroid MB. Prebiotics and synbiotics: concepts and nutritional properties. Br J Nutr. 1998 Oct;80(4):S197-202.

16.Schaafsma G, Meuling WJ, van Dokkum W, Bouley C. Effects of a milk product, fermented by Lactobacillus acidophilus and with fructo-oligosaccharides added, on blood lipids in male volunteers. Eur J Clin Nutr. 1998 Jun;52(6):436-40.

17.Swanson KS, Grieshop CM, Flickinger EA, Bauer LL, Wolf BW, Chow J, Garleb KA, Williams JA, Fahey GC Jr. Fructooligosaccharides and Lactobacillus acidophilus modify bowel function and protein catabolites excreted by healthy humans. J Nutr. 2002 Oct;132(10):3042-50.

18.Tahiri M, Tressol JC, Arnaud J, Bornet F, Bouteloup-Demange C, Feillet-Coudray C, Ducros V, Pepin D, Brouns F, Rayssiguier AM, Coudray C. Five-week intake of short-chain fructo-oligosaccharides increases intestinal absorption and status of magnesium in postmenopausal women. J Bone Miner Res. 2001 Nov;16(11):2152-60.

19.Ten Bruggencate SJ, Bovee-Oudenhoven IM, Lettink-Wissink ML, Katan MB, Van Der Meer R. Dietary fructo-oligosaccharides and inulin decrease resistance of rats to salmonella: protective role of calcium. Gut. 2004 Apr;53(4):530-5.

20.Ten Bruggencate SJ, Bovee-Oudenhoven IM, Lettink-Wissink ML, Van der Meer R. Dietary fructo-oligosaccharides dose-dependently increase translocation of salmonella in rats. J Nutr. 2003 Jul;133(7):2313-8.

21.van Dokkum W, Wezendonk B, Srikumar TS, van den Heuvel EG. Effect of nondigestible oligosaccharides on large-bowel functions, blood lipid concentrations and glucose absorption in young healthy male subjects. Eur J Clin Nutr. 1999 Jan;53(1):1-7.

EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.

Cranberry

Overview
Cranberries come form shrubs that grow in swamps either in North America or Europe. Cranberries became famous in American cuisine following the 1621 meal of Thanksgiving by the Pilgrims. Native Americans ate the berries for various complaints, including the relief of ‘bad fever’, to cleanse the stomach, relieve nausea, and treating bladder complaints. In the 1840’s, German chemists found that cranberry consumption could produce urine containing hippuric acid. At about 1900, in the U.S. it was discovered that the continual consumption of cranberries could prevent UTIs. Since that time, women have used cranberries for this purpose. Everybody seems to know of the use of cranberry juice for urinary tract infections, yet clinical evidence has been catching up to its reputation (McKenna et al., 2002).
Originally, it was thought that cranberry juice only worked by producing acidic urine. However, after there were doubts of this mechanism, it was found that cranberries prevent E. coli from adhering to the lining of the urinary tract. Cranberries are available in many forms, including juice (sweetened and non-sweetened), fresh berries, dehydrated fruit juice concentrate in capsules, berry tea, and extracts. It is important that the form of cranberry is not too diluted (as is the case of many commercial ‘cranberry’ juice) for efficacy (McKenna et al., 2002).
Comments
The reviews by Jepson et al. (2000, 2001, and 2004) are telling in that early on, little clinical evidence could be found to confirm cranberry’s efficacy. However, since the year 2000 clinical trials are becoming higher quality.
Scientific Support
Urinary Tract Infection
In a review of the clinical studies on the effectiveness of cranberry products for urinary tract infections (UTIs), Raz et al. (2004) found that approximately a dozen trials had been performed, but the trials suffered a number of limitations. One of the limitations was stated as the use of a wide variety of cranberry products, such as cranberry juice concentrate, cranberry juice cocktail, and cranberry capsules with different dosing regimens.
In a systematic review of cranberries (especially cranberry juice) on urinary tract infections (UTIs) data was collected consisting of randomized, or semi-randomized, controlled trials of cranberry juice/products. Seven trials met the criteria, and in 6 trials, the effectiveness of cranberry juice vs. water or placebo was tested, and in 2 trials the effectiveness of cranberry tablets vs. placebo was tested. Two of the well-designed randomized clinical trials provided evidence for the efficacy of cranberry juice (with significant results) over 12 months of use in women. However, it was unclear whether cranberry juice was efficacious in the other groups, and what the optimum dosage or method of administration (Jepson et al., 2004). In an earlier review with the same inclusion criteria, only 5 trials were found to meet the criteria. The reviewers concluded the trials available at that time were of small size, and too poor of quality to interpret reliable results (Jepson et al., 2001). Just one year earlier, in a similar systematic review, no trials were found to fit the inclusion criteria (Jepson, 2000).
A randomized, double-blind, placebo-controlled trial was conduced in order to determine whether antibacterial effects of cranberry juice are effective in reducing or eliminating bacteriuria and pyuria in people with spinal cord injury (SCI). Each participant was administered 2 g of concentrated cranberry juice or placebo in capsule for 6 months. Cranberry extract was not found to produce significant differences in urinary bacterial colonies from control (Waites et al., 2004).
In a randomized, placebo-controlled trial cranberry tablets (concentrated juice) were compared to cranberry juice and placebo for efficacy and cost effectiveness. The participants (women) were divided into three groups, placebo juice + placebo tablets versus placebo juice + cranberry tablets, versus cranberry juice + placebo tablets. Tablets were administered two times daily, and the juice 250 ml three times daily. Cost effectiveness was calculated as dollar cost per urinary tract infection. Both cranberry juice and tablets were found to significantly reduce the number of patients experiencing at least 1 symptomatic UTI/year. The cost of prophylaxis was $624 for cranberry tablets and $1400 for cranberry juice. Cost effectiveness ratios found cranberry tablets to be two times more cost effective than the juice for UTIs (Stothers, 2002).
Habash et al. (1999) conducted a study on the comparison of water consumption, ascorbic acid or cranberry supplements on urine acidity and other measures. Ascorbic acid was the only treatment to consistently produce acidic urine. Urine collected after cranberry or ascorbic acid both had lower initial deposition rates and numbers of Escherichia coli and Enterococcus faecalis, but not other antimicrobials; whereas, water increased deposition rates and number of E. coli and E. faecalis.
In a randomized, double-blind, placebo-controlled trial of cranberry juice on bacteriuria and pyuria in elderly women, 153 elderly women were administered either cranberry juice (300 mL daily) or placebo. The cranberry juice reduced the frequency of bacteriuria with pyuria in older women (Avorn et al., 1994).
Antioxidant Activity
Pedersen et al. (2000) conducted a placebo controlled comparison of blueberry juice to cranberry juice for increasing plasma phenolic content and antioxidant activity. The participants were given either 500 ml of blueberry juice, cranberry juice, or a sucrose solution. Blood and urine samples were collected and analyzed after consuming the juice. Cranberry juice, but not blueberry juice, produced an increase in the plasma antioxidant capacity, that may be explained by an increase in vitamin C that was absent in blueberry juice.
Safety / Dosage
A typical daily dosage that has been recommended for cranberry, is 1/2 cup for the fresh fruit, 15 mL of the dried fruit, 90 ml of the juice cocktail (1/3 of which is pure juice). For an active UTI, the dosage is increased to between 12-32 fl oz, or 390-960 mL. Some products may available on the market that are standardized to total organic acids or polyphenolic content (McKenna et al., 2002).
Cranberry juice, when taken at the recommended levels, has no known side effects. In people with tendency to developing kidney stones, the limitation of cranberry juice intake is recommended to no more than one liter per day (McKenna et al., 2002).
References
1.Avorn J, Monane M, Gurwitz JH, Glynn RJ, Choodnovskiy I, Lipsitz LA. Reduction of bacteriuria and pyuria after ingestion of cranberry juice. JAMA. 1994 Mar 9;271(10):751-4.
2.Habash MB, Van der Mei HC, Busscher HJ, Reid G. The effect of water, ascorbic acid, and cranberry derived supplementation on human urine and uropathogen adhesion to silicone rubber. Can J Microbiol. 1999 Aug;45(8):691-4.
3.Jepson RG, Mihaljevic L, Craig J. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev. 2004;(2):CD001321.
4.Jepson RG, Mihaljevic L, Craig J. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev. 2001;(3):CD001321.
5.Jepson RG, Mihaljevic L, Craig J. Cranberries for treating urinary tract infections. Cochrane Database Syst Rev. 2000;(2):CD001322.
6.McKenna, D.; K. Jones and K. Hughes. Botanical Medicines: The Desk Reference for Major Herbal Supplements. 2nd Ed. 2002 Haworth Press: Binghamton, NY. 1138 pp.
7.Pedersen CB, Kyle J, Jenkinson AM, Gardner PT, McPhail DB, Duthie GG. Effects of blueberry and cranberry juice consumption on the plasma antioxidant capacity of healthy female volunteers. Eur J Clin Nutr. 2000 May;54(5):405-8.
8.Raz R, Chazan B, Dan M. Cranberry juice and urinary tract infection.
9.Clin Infect Dis. 2004 May 15;38(10):1413-9. Epub 2004 Apr 26.
10.Stothers L. A randomized trial to evaluate effectiveness and cost effectiveness of naturopathic cranberry products as prophylaxis against urinary tract infection in women. Can J Urol. 2002 Jun;9(3):1558-62.
11.Waites KB, Canupp KC, Armstrong S, DeVivo MJ. Effect of cranberry extract on bacteriuria and pyuria in persons with neurogenic bladder secondary to spinal cord injury. J Spinal Cord Med. 2004;27(1):35-40.
EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.

Cortisol to Testosterone Ratio

Testosterone – Cortisol’s Alter Ego
originally written for Advance for Healthy Aging Journal by Shawn M. Talbott, PhD
What is Testosterone?
In both men and women, testosterone is needed to build muscle and other proteins, such as immune system components, and control many aspects of physiology, including blood cell production and metabolism of protein, carbohydrates, and fat from food. A drop in testosterone in men leads to fatigue, a loss of sex drive, and weight gain in the belly – the old potbelly that nobody wants. This same drop in testosterone causes the same fatigue and loss of sex drive in women, but it also induces women’s bodies to lose their “hourglass” shape of youth and grow into an apple (or “shot glass”) shape with the same kind of “male” pattern of abdominal weight gain.
Because of the media reports of athletes abusing anabolic steroids (synthetic versions of testosterone), testosterone has suffered a negative public image that is not deserved. Many people view testosterone as the hormone that causes bulging muscles and aggressiveness, but it is important to understand that these effects of testosterone are caused by a gross overuse of synthetic testosterone used at extreme mega-dose levels. When bodybuilders inject testosterone and other anabolic steroids to promote freakish muscle growth, they are artificially increasing their testosterone levels to 10, 20, or 100-times normal values. The result of this unnatural testosterone exposure is the clearly unnatural changes in body shape, mood, and metabolism characteristic of professional bodybuilders.
Some of the most common effects of low testosterone (in both men and women) include:

• •Emotional changes (increased anxiety and depression)

• •Low sex drive
• •Decreased muscle mass
• •Reduced metabolic rate
• •Increased abdominal fat
• •Weak bones
• •Back pain
• •Elevated cholesterol

Testosterone – not just for men
Testosterone – just for men? Hardly! Often referred to as the “hormone of desire,” testosterone is involved in maintaining muscles mass, mood, and energy levels in BOTH men and women. We have known since the mid-1980s, that testosterone is not just a “male” hormone, because it was in 1985 that researchers published the first major study showing that testosterone was vitally important in boosting and maintaining a woman’s libido, sexual arousal and desire. After the age of 30 (just like in men) testosterone levels start to drop in women. What follows is the very predictable drop in sex drive, loss of muscle mass, reduction in metabolic rate, and decrease in energy levels and mood. What goes up? You guessed it – body weight – and we see the same thing happening in both men and women.
Although women have only about one-tenth the testosterone of men, her levels drop by about half by the age of 45 (compared to the amount she produced at age 20). In a scientific review by the North American Menopause Society, 9 out of 10 studies on testosterone in women showed that restoring testosterone levels back to normal to be effective in improving sexual desire, energy levels, and overall emotional outlook.
Testosterone production in women comes from the ovaries and in men it comes from the testes – but in both genders, a substantial amount of testosterone also comes from the adrenal glands – the same gland responsible for cortisol production. During periods of high cortisol production (stress, dieting, and sleep loss), natural production of testosterone falls. Considering that women produce only about one-tenth the amount of testosterone found in men, any stressed-induced drop in testosterone would be expected to affect women as much or more than most men. The effects of stress in older women is even worse because female testosterone levels peak in the mid-twenties just as in young men – and fall every year thereafter – so you are less able to “bounce back” from a stressful event at age 40 compared to age 20.
For women who want to stay lean, strong, healthy, fit, and sexually active, maintaining a youthful testosterone level is just as important as it is for men. In fact, studies published in the New England Journal of Medicine have shown that testosterone maintenance in women (aged 31-56 years) yields the very same benefits in sexual function, mood, energy, and overall sense of well being as found in studies of men.

Maintaining Balance – the Cortisol-to-Testosterone Ratio
The balance between cortisol and testosterone is probably even more important than the absolute level of either hormone. From the perspective of achieving peak physical and mental performance, we want to have a relatively low cortisol levels and a relatively high testosterone level – a hormonal profile that we would refer to as “anabolic” to suggest fat loss and muscle gain. This anabolic hormonal profile is what athletes strive for, but it is also your target for optimal weight loss and for long-term health.
Iranian medical researchers have shown that the stress of exams (psychological stress) increases cortisol and reduces testosterone levels in both male and female students – and British researchers from the University of Bristol, have found that elevated cortisol and reduced testosterone (which we refer to as an elevated C:T ratio) increases the risk of heart disease. The study, which followed men aged 45-59 years for more than 16 years, and was published in the scientific journal of the American Heart Association, also found that the C:T ratio was strongly related to insulin resistance (pre-diabetes). Researchers from Denmark have confirmed the heart-damaging effects of stress by showing that increased cortisol and reduced testosterone are independently related to an increase in blood vessel thickening (a significant risk factor for heart disease) in both men and women. Italian researchers have shown that low testosterone is associated not only with weight gain, but also with increased levels of “bad” cholesterol, lower levels of “good” cholesterol, insulin resistance (pre-diabetes), and an overall higher risk of heart disease.
The C:T ratio is studied quite often in athletes, not only because of the performance aspects of cortisol and testosterone, but also because they represent an ideal “high stress” situation to help answer important questions about how humans adapt to chronic stress. For example, physiology researchers from the University of North Carolina have shown a clear negative relationship between cortisol levels and testosterone levels in athletes – meaning that as stress gets higher, cortisol goes up and testosterone drops. Researchers from the University of Connecticut have shown that over-trained athletes have elevated levels of sex hormone-binding globulin (SHBG – which binds testosterone and makes it unavailable to the body) and reduced testosterone levels – both of which could be prevented by dietary supplementation.

Testosterone and Aging – Menopause & Andropause
Athlete studies aside, by the time most of us reach our forties (men and women), our testosterone levels are about 20% lower compared to the levels we had as robust twenty-year-olds (no wonder we’re fatter and more exhausted). In most people, testosterone levels start to fall by about 10% per decade (1% per year) after age 20 or 30. At the same time, our bodies start to produce more of a binding protein called sex-hormone binding globulin (SHBG) – which traps most of the testosterone that is still remaining in circulation. This is bad because SHBG binds and “traps” testosterone in a way that makes it unavailable to the rest of the body – effectively reducing your “bioavailable” levels of testosterone even further.
Around age 50, women are likely to hit menopause, and experience dramatic drops in both estrogen and testosterone. While men obviously don’t experience menopause, they do have a much larger drop in testosterone levels – a change that is referred to as andropause. During this time of life, when hormone production is falling in both men and women, as many as 30% of people in their 50s will have testosterone levels low enough to cause noticeable symptoms. Some of the clearest signs of a testosterone imbalance are changes in attitude and mood, as well as a loss of energy and sex drive.
Researchers from the Mayo Clinic have documented the fall in testosterone levels to be in the range of 35-50% by age 60 in healthy men, while aging researchers from Saint Louis University have shown that testosterone levels fall 47% in men from age 20 to 89.
It is well described in the scientific and medical literature that men who have low level of testosterone are more likely to be depressed than men with normal testosterone levels. When testosterone levels are brought back to normal levels, mood also returns back to normal levels.
Dozens of studies show that maintaining testosterone levels at more “youthful” levels (that is, keeping them from dropping with age) is associated with numerous health benefits in BOTH men and women. For example, men and women with low testosterone develop abdominal obesity (belly fat), a loss in sex drive (interest and ability), and become depressed (or at least moody). Preventive medicine specialists from the University of California at San Diego have shown that high levels of stress lead to lower testosterone levels (reduced by 17%) and increase rates of depression in men over 50 years of age. Bringing testosterone levels back to normal levels reduces depression. If you look at testosterone on an overall scale – it is not a “more is better” story, but rather one of “maintaining is good” and “falling levels are bad” – it’s one of overall balance.

Testosterone and Weight Gain
Perhaps the most noticeable side effect of a falling testosterone level for many people will be their expanding waistline. Just as increasing cortisol levels can lead to excess belly fat – so can falling testosterone – and when you have both occurring simultaneously (cortisol rising and testosterone falling) it is virtually inevitable that weight gain will follow.
One study, published more than 10 years ago in the Journal of Clinical Endocrinology and Metabolism (1996) showed that obese women who boosted their testosterone levels lost significantly more abdominal fat and gained more muscle mass compared to women given a placebo and whose testosterone levels remained suppressed. This was ten long years ago – and still most doctors and health professionals view testosterone strictly as a “male” hormone – when the reality is that while women certainly don’t want “male levels” of testosterone, they certainly want to maintain what they have.
The scientific literature in support of maintaining normal youthful testosterone levels (versus allowing them to fall in the face of stress and aging) is at least as strong as the research in support of maintaining normal youthful cortisol levels (which rise in response to stress and aging).
Researchers from Penn State University have shown that weight loss induced by diet alone leads to a significant drop in testosterone and fat-free mass (muscle) – an effect that can reduce metabolic rate and make weight regain easier. Scientists from Northwestern University in Chicago have shown that weight gain in young men (ages 24-31) was significantly related to low testosterone levels – with a graded relationship between the lowest testosterone levels and the greatest degree of weight gain. In a related series of studies, researchers at Cornell Medical College in New York found that the age-related decrease in testosterone is significantly exacerbated in overweight men with the Metabolic Syndrome. As testosterone drops, body weight goes up – and the drop in testosterone and the rise in weight are more pronounced in men who have Metabolic Syndrome, compared to men without (but who also gain weight as testosterone drops, but to a less severe degree). In a very important study from aging researchers at the University of Florida, the incidence of low testosterone in a general population of men (over age 45) as estimated to be 38.7% - and those with low testosterone were about twice more likely to also be overweight and have hypertension, high cholesterol, and diabetes.
These studies represent only a small fraction of the research on the relationship between testosterone, stress, cortisol, and weight gain, but it should be clear to you by now that the failure to maintain a normal C:T balance is an important reason why weight gain (and regain) is so easy for so many people. As we lose weight, cortisol levels rise, testosterone levels drop, muscle mass and metabolic rate fall, fat cells lose the “fat breakdown” signal (testosterone) and receive the “fat storage” signal (cortisol) – and weight appears (or easily comes back).

Maintaining Testosterone Levels Naturally
Like other hormones, including cortisol, we know quite clearly that maintaining normal levels, not too high and not too low, is the approach associated with the most dramatic long-term health benefits. It is important to keep in mind that one of the most central concepts in the study of endocrinology is that hormones tend to work in concert with one another to control metabolism. This means that changing two hormones – each by a little bit – is likely to have a better overall effect on a given outcome (such as weight loss) than changing a single hormone by a large amount.
In terms of exercise, we know that virtually all forms of exercise help to elevate testosterone levels in both men and women – and endurance exercise works almost as well as lifting weights for maintaining testosterone in most moderate exercisers. Researchers at the University of Texas have shown that not only does inactivity lead to a rapid loss of muscle mass, but when accompanied by high levels of stress and cortisol, muscle loss is accelerated. The good news about exercise is that while it is boosting testosterone, it is also reducing cortisol (the “de-stressing” effect of a workout) – but the best news of all is that your patients will be pleasantly surprised by how little exercise is needed to have these positive hormonal effects.
Avoiding dehydration is another way to keep hormones balanced. Researchers from the University of Connecticut’s Human Performance Laboratory have shown that cortisol levels are increased by dehydration – and C:T ratio was significantly higher (elevated C and reduced T) – a biochemical state that interferes with the balance between anabolism and catabolism (shifting the body toward fat gain and muscle loss).
Finally, stress researchers from around the world have shown that how we perceive and cope with a given stressor can determine our hormonal response to that stressor. More important than winning or losing, is the coping pattern that you display – thus determining the hormonal changes. Psychologists at the University of Miami use CBSM – cognitive behavioral stress management – to reduce perceived stress in stressful or competitive situations. Participating in CBSM activities cause cortisol levels to drop and anabolic hormones (like testosterone and DHEA) to rise – effects which typically translate into an improvement in both mood and in immune function.

Summary
It is probably quite apparent by this point that it is the balance between anabolic and catabolic hormones that represents the “metabolic sweet spot” that your patients should be shooting for. In a perfect world, we would easily maintain our relatively high cortisol and low testosterone levels of youth. Alas, the very process of living and aging (gracefully or not) leads us inexorably toward elevated cortisol and suppressed testosterone (among many other changes) – all of which combine to make us rounder and softer and tired and less happy – unless we take proactive steps to maintain those levels.

References
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Mayes JS, Watson GH. Direct effects of sex steroid hormones on adipose tissues and obesity. Obes Rev. 2004 Nov;5(4):197-216.
McTiernan A, Tworoger SS, Rajan KB, Yasui Y, Sorenson B, Ulrich CM, Chubak J, Stanczyk FZ, Bowen D, Irwin ML, Rudolph RE, Potter JD, Schwartz RS. Effect of exercise on serum androgens in postmenopausal women: a 12-month randomized clinical trial. Cancer Epidemiol Biomarkers Prev. 2004 Jul;13(7):1099-105.
McTiernan A, Wu L, Chen C, Chlebowski R, Mossavar-Rahmani Y, Modugno F, Perri MG, Stanczyk FZ, Van Horn L, Wang CY; Women's Health Initiative Investigators. Relation of BMI and physical activity to sex hormones in postmenopausal women. Obesity (Silver Spring). 2006 Sep;14(9):1662-77.
Mohr BA, Bhasin S, Link CL, O'Donnell AB, McKinlay JB. The effect of changes in adiposity on testosterone levels in older men: longitudinal results from the Massachusetts Male Aging Study. Eur J Endocrinol. 2006 Sep;155(3):443-52.
Osuna JA, Gomez-Perez R, Arata-Bellabarba G, Villaroel V. Relationship between BMI, total testosterone, sex hormone-binding-globulin, leptin, insulin and insulin resistance in obese men. Arch Androl. 2006 Sep-Oct;52(5):355-61.
Pasquali R. Obesity and androgens: facts and perspectives. Fertil Steril. 2006 May;85(5):1319-40.
Travison TG, Araujo AB, O'donnell AB, Kupelian V, McKinlay JB. A population-level decline in serum testosterone levels in American men. J Clin Endocrinol Metab. 2006 Oct 24.
Vicennati V, Ceroni L, Genghini S, Patton L, Pagotto U, Pasquali R. Sex difference in the relationship between the hypothalamic-pituitary-adrenal axis and sex hormones in obesity. Obesity (Silver Spring). 2006 Feb;14(2):235-43.

Testosterone and Weight Gain

This is an excerpt from the upcoming book, “Vigor – Seven Days to Improved Physical Energy, Mental Focus, and Emotional Well-Being” by Shawn M. Talbott, PhD
For many people, perhaps the most noticeable side effect of a falling testosterone level will be an expanding waistline. Just as increasing cortisol levels can lead to excess belly fat, so can declining testosterone levels—and when you have both occurring simultaneously (cortisol rising and testosterone falling) it is virtually inevitable that weight gain will follow.
One study, published in 1996 in the Journal of Clinical Endocrinology and Metabolism, showed that obese women who boosted their testosterone levels lost significantly more abdominal fat and gained more muscle mass compared to women who were given a placebo and whose testosterone levels remained suppressed. This was more than a decade ago—and still most doctors and health professionals view testosterone strictly as a “male” hormone, when the reality is that while women certainly don’t want “male levels” of testosterone, they definitely want to maintain what they have.
The scientific literature in support of maintaining normal youthful testosterone levels (versus allowing them to fall in the face of stress and aging) is at least as strong as the research in support of maintaining normal youthful cortisol levels (which rise in response to stress and aging). Here is a sampling of some of the available studies:

• •Austrian medical researchers have shown that weight loss from dieting results in a significant reduction in testosterone levels in overweight women. But this effect is largely due to a high level of dieting stress caused by excessive calorie restriction (which elevates cortisol) and unbalanced with exercise (which could maintain testosterone levels). Researchers from Penn State University have shown that weight loss induced by diet alone leads to a significant drop in testosterone and fat-free mass (muscle)—an effect that can reduce metabolic rate and make weight regain easier.

• •Scientists from Northwestern University, in Chicago, have shown that weight gain in young men (ages twenty-four to thirty-one) was significantly related to low testosterone levels, with a graded relationship between the lowest testosterone levels and the greatest degree of weight gain. In a related series of studies, researchers at Cornell Medical College, in New York, found that the age-related decrease in testosterone is significantly exacerbated in overweight men with the metabolic syndrome. As testosterone drops, body weight goes up—and the drop in testosterone and the rise in weight are more pronounced in men who have metabolic syndrome than it is in men without. (Men who don’t have the condition also gain weight as testosterone drops, but to a less severe degree.)
• •As part of the Massachusetts Male Aging Study (which followed over seventeen hundred men, ages forty to seventy), researchers at the New England Research Institutes found that overweight men had significantly lower testosterone levels and a greater rate of decline compared to normal-weight men of any age. Endocrine researchers from Venezuela have found that testosterone levels are lower in overweight men ages twenty to sixty, and that there is a graded and proportional relationship between low testosterone and weight gain (the fattest men had the lowest testosterone).
• •Norwegian medical researchers have shown that the lowest levels of testosterone are found in men with the most pronounced central (abdominal) obesity. In addition, those with lower testosterone also had higher blood pressure and increased rates of diabetes. These findings suggest that testosterone may have a protective effect against weight gain and development of diabetes and hypertension.
• •In a very important study from researchers in aging at the University of Florida, the incidence of low testosterone in a general population of men over age forty-five was estimated to be 38.7 percent. Those with low testosterone were about twice as likely to also be overweight and have hypertension, high cholesterol, and diabetes.
• •In a study from researchers at the Albert Einstein College of Medicine, in New York, overweight men were shown to have reduced testosterone levels, with the lowest levels seen in men who continued to gain weight over time (eight years follow-up). Interestingly, the level of testosterone was found to predict subsequent weight gain: Lower testosterone related specifically to increased weight gain in the abdominal area.
• •Australian scientists at the University of Adelaide have shown that testosterone levels decline with aging even in healthy men—and also lead to obesity and metabolic syndrome.
• •Italian hormone researchers have shown a negative relationship between C:T ratio and obesity in men and women. As stress-related cortisol levels rise, testosterone levels drop in both sexes, leading to weight gain, especially within the abdominal area.
• •Public-health researchers from Hong Kong have shown that age-related declines in testosterone are associated with increased levels of abdominal fat and higher rates of the metabolic syndrome. In a series of studies, low testosterone levels explained 35 percent of the variance in metabolic syndrome rates (more metabolic syndrome equated with lower testosterone).
• •Brazilian medical researchers have found low testosterone levels to be strongly associated with weight gain and specifically with higher abdominal fat (waist-to-hip ratio). Norwegian researchers have shown that the lowest testosterone levels are found in subjects with high waist circumference, even when their total level of body fat is rather normal, suggesting that waist circumference (abdominal fat) is the preferred anthropometric measurement to predict testosterone levels (bigger waist = lower testosterone).
• •Health researchers from Oklahoma State University have demonstrated a direct effect of testosterone on adipose tissues (fat cells) and obesity, showing that testosterone leads to an increase in lipolysis (fat breakdown). Normal testosterone levels lead to a normal distribution of body fat, but as testosterone levels decrease in response to stress and aging, there is a tendency to increase central obesity (gain abdominal fat). In fact, bringing testosterone levels back to within normal ranges in older men and women has been shown to reduce the degree of central obesity.
• •Researchers at the University of Washington, in Seattle, have shown that among women who lose weight using dietary restriction alone, each 2 percent loss of body weight is associated with a fall in testosterone levels of 10 to 12 percent.

These studies represent only a fraction of the research on the relationship between testosterone, stress, cortisol, and weight gain, but it should be clear to you by now that the failure to maintain a normal C:T balance is an important reason why weight gain (and regain) is so easy for so many people. As we attempt to lose weight, our bodies try to “fight back” by slowing metabolism and conserving body fat through a rise in cortisol levels, a drop in testosterone levels, and a decline in muscle mass and metabolic rate. As a result of these metabolic changes, fat cells lose the “fat-breakdown” signal (testosterone) and receive the “fat-storage” signal (cortisol)—and weight appears (or easily comes back).

Hormones and Belly Fat?

A colleague of mine forwarded an interesting study to me the other day (Obesity, Aug 20, 2009 – Janssen et al.). The study, from researchers at Rush University in Chicago, had been covered in some of the national news media and it suggested that testosterone levels were associated with belly fat in postmenopausal women. This recent finding confused my colleague because there are hundreds of other research trials (in men, premenopausal, and postmenopausal women) suggesting just the OPPOSITE effect (that higher testosterone levels are generally associated with a reduction in belly fat levels).
The main difference between this recent study (and several others like it) is that it is a study of “statistical correlations” (indicating that levels of one thing are related in some way to levels of another thing) – rather than a study of a specific “intervention” (such as actually altering testosterone levels and measuring a change in belly fat levels). Such statistical correlations (i.e. X is related to Y) often have no relationship to “causality” – meaning that one thing does not necessarily cause or lead to the other (think about a rooster crowing when the sun comes up in the morning – the two events of crowing and sunrise are correlated, but the rooster does not cause the sun to rise). Such correlation studies are still valuable to scientists because they provide guidance for future intervention studies – but you actually need to DO those interventions to prove out the theories generated by the statistical correlations.
Consider another recent study published in the journal Metabolism (June 2008) – researchers from Columbia University found a correlation between belly fat and testosterone levels in postmenopausal women. However, if you looked at the actual characteristics of the women in the study, you see that the women with the lowest testosterone levels in fact had the highest levels of belly fat. In fact, a 30% reduction in levels of either total testosterone or free testosterone (the bioavailable type) was associated with almost TRIPLE the belly fat compared to women with higher testosterone levels (292% higher belly fat levels in women with a 28%-30% reduction on testosterone levels). The women with the lowest testosterone levels also had the most belly fat, the most total body fat, the highest body weight, and the largest waist circumference.
Obviously, overall metabolic balance in the human body is a much more complex picture than simply drawing a straight line from one hormone to one effect in the body – and it is the maintenance of balance that seems to be the most important consideration for improving or maintaining health and well-being. In addition to the studies that my own group has conducted and presented at some of the leading scientific conferences (American College of Sports Medicine, American College of Nutrition, International Society for Sports Nutrition, The Obesity Society, American Society for Nutritional Sciences), when we are able to naturally maintain metabolic balance (i.e. ratio between cortisol and testosterone) we are also able to measure significant improvements in mood state, body fat, and levels of fatigue and depression (see slides and abstracts from these peer-reviewed scientific conferences at www.WisdomOfBalance.com).
Thanks for reading – until next time…
Shawn
================
Shawn M. Talbott, PhD LDN FACSM
smtalbott@mac.com
www.ShawnTalbott.com
smtalbott@supplementwatch.com
www.SupplementWatch.com

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Evening Primrose Oil

Overview
Evening Primrose Oil (EPO) is made from the seeds of the herb Oenothera biennis that grows wild in arid environments such as sand dunes. True to its name, evening primrose flowers (bright yellow) open in the evening and fade in bright sunlight. First documented medicinally in England, evening primrose oil is most commonly used for relieving premenstrual syndrome, fibrocystic breasts, and menopausal symptoms such as hot flashes.

Comments
It appears that evening primrose oil may be a useful alternative to prescription medication for symptoms of PMS, especially breast pain associated with the menstrual cycle. Perhaps the most promising use for evening primrose oil is its cardioprotective effect delivered by its profile of anti-inflammatory fatty acids.

Scientific Support
Sixty to 80% of evening primrose oil is the essential (not produced by the body) fatty acid, linoleic acid. Gamma linoleic acid (GLA) is synthesized by the body from linoleic acid and comprises 8-14% of the oil. GLA is a precursor of prostaglandin E1 (PGE1) - the deficiency of which has been documented in some women with premenstrual syndrome (PMS) and cyclical breast pain (Bendich 2000, Bordoni et al. 1987). Since decreased levels of PGE1 can increase the pain-inducing effects of the hormone prolactin on breast tissue, it is thought that low PGE1 levels may be a primary cause of many of the symptoms associated with PMS (Cheung 1999).

In addition to its applications for specific detrimental effects of the menstrual cycle, theories for non-gender related uses for evening primrose oil are prevalent. PGE1 has beneficial anti-inflammatory, blood-thinning and vasodilating properties (Dirks et al. 1998). Also, since GLA increases PGE1 levels, supplementation with evening primrose oil could theoretically provide benefits in rheumatoid arthritis and coronary artery disease (Laivuori et al. 1993). Because essential fatty acids are claimed to have positive effects on certain skin diseases, supplementation with evening primrose oil, comprised mostly of essential fatty acids, could also alleviate eczema and dermatitis. Finally, people with GLA deficiencies are thought to produce more fat in their bodies – so theories abound for evening primrose oil supplements to promote fat loss.

Most scientific literature related to evening primrose oil supplementation involves its use for promoting well-being during the menstrual cycle. In two controlled studies, subjects received 4-6 grams of evening primrose oil or placebo for 3-4 months – but neither trial was able to demonstrate a significant benefit of the supplements (Horrobin 1983, Horrobin 1993). It is worth noting, however, that other placebo-controlled studies have shown significant benefits of supplementation with evening primrose oil, but only after 6 months of treatment (Chenoy et al. 1994, Collins et al. 1993). In the treatment of cyclic breast pain, evening primrose oil has been found to be more effective than placebo (44% versus 19%, respectively) and when compared to treatment with the prescription drugs (bromocriptine and danazol), evening primrose oil was as effective as bromocriptine, but less effective than danazol in alleviating breast pain (Huntley and Ernst 2003). In one well-controlled study to evaluate the use of evening primrose oil for the relief of hot flashes associated with menopause, 56 women were treated for 6 months with either 4 grams of evening primrose oil, or placebo – but no significant benefits were attributed to taking evening primrose oil for treatment of menopausal symptoms (Huntley and Ernst 2003).

Perhaps the most convincing evidence for supplementing with evening primrose oil involves its use in those with coronary artery disease. A study in 10 patients with high cholesterol levels showed that 3.6 grams of evening primrose oil taken daily for 8 weeks significantly decreased LDL (“bad”) cholesterol by 9% (Cern et al. 1993). However, for patients with high triglyceride and cholesterol levels, no such reductions occurred. In a double-blind crossover study in men taking either fish oil alone or fish oil plus evening primrose oil, the combination lead to a significant 12% decrease in atherogenic markers, whereas fish oil alone lead to a nonsignificant 6% decrease in the same markers (Brzeski et al. 1991).

There are many other claims for the use of evening primrose oil, though the scientific findings are rather disappointing. In a 6-week, double-blind, placebo-controlled study of 58 children who required treatment with topical skin steroids for atopic dermatitis (22 of which also had asthma), no significant difference was found between the placebo and the evening primrose oil group (Schafer and Kragballe 1991). Likewise, no effect was seen in terms of asthma symptoms. In a 24-week, double-blind, placebo-controlled study of 39 patients with chronic hand dermatitis (Whitaker et al. 1996), no therapeutic value was shown following 600mg of daily GLA supplements (compared to placebo). No scientific evidence is available to support any benefit of evening primrose oil in alleviating rheumatoid arthritis or in aiding weight loss.

Safety/Dosage
Evening primrose oil appears to be quite safe. Potential adverse effects include gastrointestinal upset and headache. Because evening primrose oil hinders platelet aggregation, this supplement may increase the anti-coagulant effect of drugs such as warfarin. Therefore, anyone taking anti-coagulants should consult with his/her personal physician before taking evening primrose oil. The most common dose of evening primrose oil is 1-4 grams per day with approximately 10% GLA.

References
1.Bendich A. The potential for dietary supplements to reduce premenstrual syndrome (PMS) symptoms. J Am Coll Nutr. 2000 Feb;19(1):3-12.
2.Blommers J, de Lange-De Klerk ES, Kuik DJ, Bezemer PD, Meijer S. Evening primrose oil and fish oil for severe chronic astalgia: a randomized, double-blind, controlled trial. Am J Obstet Gynecol. 2002 Nov;187(5):1389-94.
3.Bordoni A, Biagi PL, Turchetto E, Serroni P, De Jaco AP, Orlandi C. Treatment of premenstrual syndrome with essential fatty acids. G Clin Med. 1987 Jan;68(1):23-8.
4.Brzeski M, Madhok R, Capell HA. Evening primrose oil in patients with rheumatoid arthritis and side-effects of non-steroidal anti-inflammatory drugs. Br J Rheumatol. 1991 Oct;30(5):370-2.
5.Budeiri D, Li Wan Po A, Dornan JC. Is evening primrose oil of value in the treatment of premenstrual syndrome? Control Clin Trials. 1996 Feb;17(1):60-8.
6.Cerin A, Collins A, Landgren BM, Eneroth P. Hormonal and biochemical profiles of premenstrual syndrome. Treatment with essential fatty acids. Acta Obstet Gynecol Scand. 1993 Jul;72(5):337-43.
7.Chenoy R, Hussain S, Tayob Y, O'Brien PM, Moss MY, Morse PF. Effect of oral gamolenic acid from evening primrose oil on menopausal flushing. BMJ. 1994 Feb 19;308(6927):501-3.
8.Cheung KL. Management of cyclical mastalgia in oriental women: pioneer experience of using gamolenic acid (Efamast) in Asia. Aust N Z J Surg. 1999 Jul;69(7):492-4.
9.Collins A, Cerin A, Coleman G, Landgren BM. Essential fatty acids in the treatment of premenstrual syndrome. Obstet Gynecol. 1993 Jan;81(1):93-8.
10.Dirks J, van Aswegen CH, du Plessis DJ. Cytokine levels affected by gamma-linolenic acid. Prostaglandins Leukot Essent Fatty Acids. 1998 Oct;59(4):273-7.
11.Douglas S. Premenstrual syndrome. Evidence-based treatment in family practice. Can Fam Physician. 2002 Nov;48:1789-97.
12.Girman A, Lee R, Kligler B. An integrative medicine approach to premenstrual syndrome. Am J Obstet Gynecol. 2003 May;188(5 Suppl):S56-65.
13.Goldfien A. Premenstrual syndrome. Curr Ther Endocrinol Metab. 1994;5:219-22.
14.Hardy ML. Herbs of special interest to women. J Am Pharm Assoc (Wash). 2000 Mar-Apr;40(2):234-42.
15.Hederos CA, Berg A. Epogam evening primrose oil treatment in atopic dermatitis and asthma. Arch Dis Child. 1996 Dec;75(6):494-7.
16.Horrobin DF, Morse PF. Evening primrose oil and atopic eczema. Lancet. 1995 Jan 28;345(8944):260-1.
17.Horrobin DF. Evening primrose oil and premenstrual syndrome. Med J Aust. 1990 Nov 19;153(10):630-1.
18.Horrobin DF. The effects of gamma-linolenic acid on breast pain and diabetic neuropathy: possible non-eicosanoid mechanisms. Prostaglandins Leukot Essent Fatty Acids. 1993 Jan;48(1):101-4.
19.Horrobin DF. The role of essential fatty acids and prostaglandins in the premenstrual syndrome. J Reprod Med. 1983 Jul;28(7):465-8.
20.Huntley AL, Ernst E. A systematic review of herbal medicinal products for the treatment of menopausal symptoms. Menopause. 2003 Sep-Oct;10(5):465-76.
21.Johnson SR. Premenstrual syndrome therapy. Clin Obstet Gynecol. 1998 Jun;41(2):405-21.
22.Khoo SK, Munro C, Battistutta D. Evening primrose oil and treatment of premenstrual syndrome. Med J Aust. 1990 Aug 20;153(4):189-92.
23.Kleijnen J. Evening primrose oil. BMJ. 1994 Oct 1;309(6958):824-5.
24.Laivuori H, Hovatta O, Viinikka L, Ylikorkala O. Dietary supplementation with primrose oil or fish oil does not change urinary excretion of prostacyclin and thromboxane metabolites in pre-eclamptic women. Prostaglandins Leukot Essent Fatty Acids. 1993 Sep;49(3):691-4.
25.Martens-Lobenhoffer J, Meyer FP. Pharmacokinetic data of gamma-linolenic acid in healthy volunteers after the administration of evening primrose oil (Epogam). Int J Clin Pharmacol Ther. 1998 Jul;36(7):363-6.
26.Schafer L, Kragballe K. Supplementation with evening primrose oil in atopic dermatitis: effect on fatty acids in neutrophils and epidermis. Lipids. 1991 Jul;26(7):557-60.
27.Veale DJ, Torley HI, Richards IM, O'Dowd A, Fitzsimons C, Belch JJ, Sturrock RD. A double-blind placebo controlled trial of Efamol Marine on skin and joint symptoms of psoriatic arthritis. Br J Rheumatol. 1994 Oct;33(10):954-8.
28.Whitaker DK, Cilliers J, de Beer C. Evening primrose oil (Epogam) in the treatment of chronic hand dermatitis: disappointing therapeutic results. Dermatology. 1996;193(2):115-20.

EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS

Flaxseed Oil

Overview

Flaxseed (also known as linseed) is just what it sounds like - the seed of the flax plant. The typical use of flaxseed is as a source (from the oil of the seeds) of the essential fatty acids linolenic acid (LN) and linoleic acid (LA). Flaxseed oil is about 57% LN (an omega-3) and about 17% LA (an omega-6). LN can be converted into eicosapentaonic acid (EPA) and decosahexanoic acid (DHA) - fatty acids which are precursors to anti-inflammatory and anti-atherogenic prostaglandins. Another beneficial ingredient found in abundance in flax seed is lignan - a phytochemical with potential for cancer prevention.

Comments

Flax seed oil is typically used as a dietary supplement for reducing symptoms of PMS and menopause (for which the evidence is thin) and for reducing inflammation and treating various inflammatory conditions such as pain, heart disease, eczema, and psoriasis (where the evidence is modest, but the theory strong based on findings with other fatty acids such as those from fish oil).

Scientific Support

Some of the health benefits associated with flaxseed consumption may be due to the presence of compounds known as lignans, which are known to possess various pro- and anti-estrogenic properties. Studies have shown that large doses (several grams) of flaxseed oil each day can reduce blood clotting by reducing platelet aggregation (Allman et al. 1995). Regular flaxseed consumption has also been associated with improvements in the ratio of omega-3 to omega-6 fatty acids in the blood - a situation which may offer protection from atherogenesis and relief from inflammatory conditions (Layne et al. 1996). A number of animal studies have shown a beneficial role of flaxseed oil in delaying breast cancer progression and protecting against colon cancer - sometimes as much as a 50% reduction compared to control groups not fed flaxseed. A clear and consistent reduction in pro-inflammatory markers (tumor necrosis factor and interleukin) has been noted in human subjects supplemented with flaxseed oil (Mest et al. 1983) – but long-term studies showing reductions in disease risk are lacking (McManus et al. 1996).

Safety/Dosage

Effective doses of flaxseed or flaxseed oil of 30-60 grams per day (2-4 tablespoons or 1-2 ounces) are unlikely to pose any adverse side effects. A note of caution is warranted, however, in cases of compromised blood clotting due to the tendency of flaxseed oil to reduce platelet aggregation and prolong bleeding times. A similar cautionary note is advisable for individuals undergoing surgical procedures - which may predispose the patient to excessive bleeding.

References

1.Allman MA, Pena MM, Pang D. Supplementation with flaxseed oil versus sunflowerseed oil in healthy young men consuming a low fat diet: effects on platelet composition and function. Eur J Clin Nutr. 1995 Mar;49(3):169-78.

2.Beitz J, Mest HJ, Forster W. Influence of linseed oil diet on the pattern of serum phospholipids in man. Acta Biol Med Ger. 1981;40(7-8):K31-K35.

3.Francois CA, Connor SL, Bolewicz LC, Connor WE. Supplementing lactating women with flaxseed oil does not increase docosahexaenoic acid in their milk. Am J Clin Nutr. 2003 Jan;77(1):226-33.

4.Layne KS, Goh YK, Jumpsen JA, Ryan EA, Chow P, Clandinin MT. Normal subjects consuming physiological levels of 18:3(n-3) and 20:5(n-3) from flaxseed or fish oils have characteristic differences in plasma lipid and lipoprotein fatty acid levels. J Nutr. 1996 Sep;126(9):2130-40.

5.Mantzioris E, James MJ, Gibson RA, Cleland LG. Dietary substitution with an alpha-linolenic acid-rich vegetable oil increases eicosapentaenoic acid concentrations in tissues. Am J Clin Nutr. 1994 Jun;59(6):1304-9.

6.Mantzioris E, James MJ, Gibson RA, Cleland LG. Differences exist in the relationships between dietary linoleic and alpha-linolenic acids and their respective long-chain metabolites. Am J Clin Nutr. 1995 Feb;61(2):320-4.

7.McManus RM, Jumpson J, Finegood DT, Clandinin MT, Ryan EA. A comparison of the effects of n-3 fatty acids from linseed oil and fish oil in well-controlled type II diabetes. Diabetes Care. 1996 May;19(5):463-7.

8.Mest HJ, Beitz J, Heinroth I, Block HU, Forster W. The influence of linseed oil diet on fatty acid pattern in phospholipids and thromboxane formation in platelets in man. Klin Wochenschr. 1983 Feb 15;61(4):187-91.

9.Morton MS, Wilcox G, Wahlqvist ML, Griffiths K. Determination of lignans and isoflavonoids in human female plasma following dietary supplementation. J Endocrinol. 1994 Aug;142(2):251-9.

10.Pang D, Allman-Farinelli MA, Wong T, Barnes R, Kingham KM. Replacement of linoleic acid with alpha-linolenic acid does not alter blood lipids in normolipidaemic men. Br J Nutr. 1998 Aug;80(2):163-7.

11.St-Onge MP, Lamarche B, Mauger JF, Jones PJ. Consumption of a functional oil rich in phytosterols and medium-chain triglyceride oil improves plasma lipid profiles in men. J Nutr. 2003 Jun;133(6):1815-20.

12.Tarpila S, Aro A, Salminen I, Tarpila A, Kleemola P, Akkila J, Adlercreutz H. The effect of flaxseed supplementation in processed foods on serum fatty acids and enterolactone. Eur J Clin Nutr. 2002 Feb;56(2):157-65.

13.Wallace FA, Miles EA, Calder PC. Comparison of the effects of linseed oil and different doses of fish oil on mononuclear cell function in healthy human subjects. Br J Nutr. 2003 May;89(5):679-89.

EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS

Alpha-Lipoic Acid

Overview

Alpha lipoic acid is a sulfur-containing fatty acid compound found in the mitochondria – the energy producing structures found in our cells. As a dietary supplement, alpha-lipoic acid (also known as lipoic acid and thioctic acid) may act as a powerful antioxidant, where it may work in synergy with other nutritional antioxidants like vitamins C and E to help prevent cellular damage from free radicals. Alpha-lipoic acid has also been shown to help control blood sugar levels in patients with diabetes.

Although alpha lipoic acid is involved in cellular energy production, its chief role as a dietary supplement may be as a powerful antioxidant. The body appears to be able to manufacture enough alpha-lipoic acid for its metabolic functions (as a co-factor for a number of enzymes involved in converting fat and sugar to energy), but the excess levels provided by supplements allow alpha-lipoic acid to circulate in a “free” state (outside of the cells where it is usually found). In this state, alpha-lipoic acid has functions as both a water- and fat-soluble antioxidant. This unique ability of alpha-lipoic acid to be active in both water and lipid compartments of the body is important because most antioxidants, such as vitamins C and E, are effective in only one area or the other. For instance vitamin C is usually restricted to the interior compartment of cells and the aqueous (“watery”) portion of blood, while vitamin E embeds itself in the lipid (“fatty”) portion of cell membranes. Adding to the potential importance of alpha-lipoic acid is its role in the production of glutathione, one of the chief cellular antioxidants produced directly by the body.

Comments

If alpha-lipoic acid were just another antioxidant, then its value would be far less. After all, there are dozens of ingredients on the market that have powerful antioxidant functions. The unique qualities possessed by alpha-lipoic acid, functioning as both a water- and fat-soluble antioxidant as well as its role in increasing the overall function of other dietary antioxidants, make it an intriguing supplement worthy of serious consideration – especially for people with diabetes because of its particular benefits in potentially preventing some forms of diabetic peripheral and autonomic neuropathy.

Scientific Support

In animal studies and human trials, alpha-lipoic acid supplementation has been shown to improve several indices of metabolic activity and lower the degree of oxidative stress (Androne et al. 2000, Arivazhagan et al. 2000). Alpha-lipoic acid supplementation may also help to reverse the decline in mitochondrial energy production that is commonly observed during the “normal” aging process (Ames 2003). Physical activity levels in animals can be increased by approximately 3-fold when supplemented with alpha-lipoic acid (Hagen et al. 1999), suggesting a beneficial effect on energy metabolism (Khanna et al. 1998). Levels of other antioxidants, such as glutathione and ascorbic acid, were also elevated in animals consuming alpha-lipoic acid, suggesting that the supplement may help protect and/or recycle these antioxidants and contribute to the overall capacity of the body to neutralize free radical damage (Packer et al. 1997, Packer et al. 1995).

In conjunction with other antioxidants, such as vitamin E, alpha-lipoic acid may be particularly helpful in patients with diabetes. By promoting the production of energy from fat and sugar in the mitochondria, glucose removal from the bloodstream may be enhanced and insulin function improved. Indeed, alpha-lipoic acid has been shown to decrease insulin resistance and is prescribed frequently in Europe as a treatment for peripheral neuropathy (nerve damage) associated with diabetes. In the U.S., the American Diabetes Association has suggested that alpha-lipoic acid plus vitamin E may be helpful in combating some of the health complications associated with diabetes, including heart disease, vision problems, nerve damage and kidney disease. Alpha-lipoic acid has also been implicated in helping to protect the brain from damage following a stroke.

There is a consistent body of evidence that intravenous infusions of alpha-lipoic acid are associated with a reduction in sensory symptoms of diabetic neuropathy (Ametov et al. 2003, Ziegler et al 2004) and that benefits are seen within 8-14 days of treatment on measures of pain, burning, numbness in patients receiving alpha-lipoic acid supplements. In human feeding studies (as opposed to studies of intravenous infusions of lipoic acid where most of the positive results exist for diabetic neuropathy), a handful of studies demonstrate that dietary supplementation with alpha-lipoic acid is able to help prevent hyperglycemia (Kinrad et al. 1999) and improve energetic substrates in muscle cells (Burke et al. 2003).

Safety / Dosage

Although there have been relatively few feeding studies conducted with alpha-lipoic acid in humans, it appears to be safe as a dietary supplement. Intakes of as much as 600mg per day have been used for treatment of diabetic neuropathy, with no serious side effects. General recommendations for antioxidant benefits typically call for 50 – 100mg per day as a general antioxidant, with higher levels of 300-600mg/day for preventing/treating complications of diabetes.

References

1.Ames BN. The metabolic tune-up: metabolic harmony and disease prevention. J Nutr. 2003 May;133(5 Suppl 1):1544S-8S.

2.Ametov AS, Barinov A, Dyck PJ, Hermann R, Kozlova N, Litchy WJ, Low PA, Nehrdich D, Novosadova M, O'Brien PC, Reljanovic M, Samigullin R, Schuette K, Strokov I, Tritschler HJ, Wessel K, Yakhno N, Ziegler D; SYDNEY Trial Study Group. The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid: the SYDNEY trial. Diabetes Care. 2003 Mar;26(3):770-6.

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EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS