The Secret to Clean Arteries

The Secret to Clean ArteriesParaoxonase-1, better known as PON-1, is the secret to clean arteries. This enzyme plays a critical role in protecting arteries from plaque build-up by enhancing the removal of cholesterol from the walls of arteries. PON-1 is attached to high-density lipoproteins (HDL).

PON-1 does more than just cleanse arterial walls of plaque, it also protects against lipid oxidation. Oxidized fats and cholesterol are more prone to stick to artery walls, creating unstable plaques. Unstable plaques rupture, causing rapid occlusion of blood flow to vital organs such as the heart and brain.

PON-1 helps to stabilize plaques by inhibiting chronic inflammation and platelet activation—factors that can all lead to plaque rupture.

As humans age, PON-1 levels markedly decline, thereby reducing the ability of HDL to protect against heart attack and stroke. This phenomenon helps explain the onset of accelerated atherosclerosis; where within a period of only a few years, an aging person’s healthy arteries rapidly occlude with plaque.

The age-related reduction in PON-1 may also explain studies showing that statin drugs lose their benefit in certain aging populations, since the effects of statins are no longer sufficient to protect against the multiple factors involved in the development of atherosclerosis in the elderly.1-3

How to Boost PON-1 Activity

1. Pomegranate

The most recent research indicates that pomegranate and its extracts can significantly elevate levels of PON-1 activity in the body. Pomegranate does this through a number of distinct biomolecular pathways that include combating inflammation and LDL adhesion and favorably modulating gene expression.

Pomegranate extracts reduce oxidation and inflammation largely through their effect on PON-1 activity, intervening at each step in the development of atherosclerosis.4

2. Resveratrol

Strong evidence has recently emerged for several compounds with known cardio-protective effects that may also favorably increase your PON-1 levels.

Moderate consumption of wine, beer, and spirits is associated with an increase in PON-1 activity. Red wine polyphenols increase PON-1 activity and reduce LDL oxidation.

Resveratrol is the best-known of the red wine polyphenols. It exerts powerful control over the PON-1 gene, increasing PON-1 expression in human liver cells and protecting against atherosclerosis in animal models.5

3. Quercetin

Quercetin is another polyphenol found in red wine and many other plant sources. It also up-regulates PON-1 gene expression, protecting against fat and cholesterol oxidation.

Quercetin possesses numerous mechanisms that help stabilize and preserve PON-1 activity against oxidative stress.6

References

  1. Okumachi Y, Yokono K. Anti-aging medicine: the evidence to the value of the antihypertensive drugs, hypoglycemic drugs and statins. Nippon Rinsho. 2009 Jul;67(7):1372-6.
  2. Kekes E. Combined antihypertensive and antilipemic therapy as one of the pillars in the poly-pharmacologic preventive strategy for patients with high cardiovascular risk. Orv Hetil. 2008 Sep 28;149(39):1827-37.
  3. Gouedard C, Koum-Besson N, Barouki R, Morel Y. Opposite regulation of the human paraoxonase-1 gene PON-1 by fenofibrate and statins. Mol Pharmacol. 2003 Apr;63(4):945-56.
  4. Aviram M, Dornfeld L, Rosenblat M, et al. Pomegranate juice consumption reduces oxidative stress, atherogenic modifications to LDL, and platelet aggregation: studies in humans and in atherosclerotic apolipoprotein E-deficient mice. Am J Clin Nutr. 2000 May;71(5):1062-76.
  5. Do GM, Kwon EY, Kim HJ, et al. Long-term effects of resveratrol supplementation on suppression of atherogenic lesion formation and cholesterol synthesis in apo E-deficient mice. Biochem Biophys Res Commun. 2008 Sep 12;374(1):55-9.
  6. Aviram M, Rosenblat M, Billecke S, et al. Human serum paraoxonase (PON 1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants. Free Radic Biol Med. 1999 Apr;26(7-8):892-904.

Summer is Here … Protect Your Skin from the Inside Out

Summer is Here ... Protect Your Skin from the Inside OutExcessive sun exposure can lead to premature aging of the skin; which means more wrinkles and discolorations. Although topical sunscreens remain the top choice of consumers, there is a new oral method for protecting your skin … Polypodium leucotomos.

Much has been written about how the sun’s burning ultraviolet rays harm our health and appearance. Yet despite the warnings, more than two million people in the US will be diagnosed with skin cancer this year alone. Rates of melanoma — the most dangerous form of skin cancer — have not only doubled over the past 10-20 years, but continue to rise 3% to 7% annually.1

A recent study found that a new oral supplement sourced from the fern, Polypodium leucotomos, could potentially become an important anti-aging ingredient for the skin.2  Extracts from the fern have been used in South America for many years to protect against the damaging effects caused by excessive sun exposure.

This amazing fern also protects skin cells from the consequences of excessive ultraviolet radiation by reducing sun-induced injury.3 Additionally, it helps ease skin inflammation and blocks protein-destroying skin enzymes.3,4

Polypodium leucotomos extract also contains a high percentage of potent antioxidants (phenolics) which block the formation of dangerous free radicals and the oxidative damage that results from excessive sun exposure.5

Remember, for long periods of sun exposure, you should defend your skin against premature aging with an oral extract from Polypodium leucotomos and a topical sunscreen to ensure complete sun protection.

References

  1. Available at: http://www.medscape.com/viewarticle/470300_2. Accessed May 3, 2010.
  2. Philips N, Conte J, Chen YJ, et al. Beneficial regulation of matrixmetalloproteinases and their inhibitors, fibrillar collagens and transforming growth factor-beta by Polypodium leucotomos, directly or in dermal fibroblasts, ultraviolet radiated fibroblasts, and melanoma cells. Arch Dermatol Res. 2009 Aug;301(7):487-95.
  3. J Photochem Photobiol B. 2006 Mar 1;82(3):173-9.
  4. J Dermatol Sci. 2003 Jun;32(1):1-9.
  5. Ann Intern Med. 1971 Dec;75(6):873-80.

Ageless Skin from a Pill? A Secret to Save Your Skin from Accelerated Aging

By Steven V. Joyal, MD

Stopping  Heart DiseaseYou want flawless, smooth skin.

You don’t smoke, you drink plenty of water every day, and you eat a diet low in refined starches and sugars. You consume adequate amounts of omega-3 fatty acids from fish, walnuts, and flax seed. You apply expensive skin cleansers and moisturizers that promise ageless, beautiful skin. Of course, you’ve heard about the dangers of excessive sun exposure and the veritable explosion in cases of diagnosed skin cancer within the past decade, so you are prudent when venturing outdoors. You wear sunscreen whenever you go to the beach or spend extended time outside, wear a broad-brimmed hat, and minimize time spent during earth’s peak period for solar radiation (generally between 11AM and 3PM in late spring,  summer, and early fall). You obtain the benefits of vitamin D from supplementation with low-cost cholecalciferol (vitamin D3) as well as ingesting foods (e.g. salmon, mushrooms) rich in this critical hormone-vitamin rather than subjecting your skin to age-accelerating solar radiation.

However, do you guard against incidental solar radiation?

Most people are completely unaware that over 80% of lifetime sun exposure occurs unintentionally. Furthermore, those unsightly brown and tan age spots that occur on exposed areas of the skin are caused by accumulated sun exposure over many years.

Unless you never the leave the house if not slathered in high sun protection factor (SPF) sunscreen or make-up, ultraviolet radiation is aging your skin (not to mention increasing your risk of skin cancer). And don’t think that just because you use a so-called “long-lasting” topical sunscreen that is “water-proof” you’re safe – close scrutiny of scientific data reveals that although newer sunscreen formulas offer enhanced resistance to the effects of sweat and swimming, these topical formulas must be re-applied frequently for maximal protection.

However, an amazing, natural plant extract, when orally ingested, offers the promise of additional protection against the damaging effects of incidental solar radiation exposure with a strong scientific portfolio of evidence.

Polypodium leucotomos is a type of fern native to certain tropical and subtropical regions of the Americas such as Honduras. Experimental studies with extracts of polypodium leucotomos have shown potent antioxidant effects. Other experimental studies show that Polypodium leucotomos extract reduces pro-inflammatory cytokines, chemicals that damage tissues when produced in excess. For over thirty years, extracts of Polypodium leucotomos have been used in Europe, Central, and South America to protect against the damaging effects of skin sensitizers and ultraviolet light therapy for the treatment of patients with psoriasis, an inflammatory skin condition characterized by silvery plaques on the skin. A clinical study showed that psoriasis patients’ skin had significantly less damage from ultraviolet light when these volunteers were given an extract of Polypodium as compared with those study volunteers given placebo. Another clinical study in patients with vitiligo (a skin condition characterized by areas of unsightly skin color mottling) showed improvement in areas of skin depigmentation when treated with ultraviolet light and 250 mg. three times daily of Polypodium leucotomos extract compared with placebo.

Make no mistake – supplementing with Polypodium leucotomos extract will not protect your skin from sunburn if you decide to spend ten hours at Fort Lauderdale beach after hibernating indoors for three months of winter. However, this natural ingredient is a wonderful adjunct to an over-all skin saving regimen that helps preserve youthful skin tone and texture. Although Polypodium will not reverse the appearance of heavily sun damaged skin, this fern extract offers the promise of lessening the impact of incidental sun exposure, now and in the future, on our skin. Since about 80% of our lifetime accumulated sun exposure is incidental, Polypodium extract represents a breakthrough strategy in the form of a dietary supplement that can help guard our skin from accelerated aging.

Stopping Heart Disease: Seven Lifesaving Blood Tests Your Doctor Doesn’t Order!

By Steven V. Joyal, MD

Stopping  Heart Disease Consider a beautiful Sunday afternoon in springtime, the smell of flowers, trees, and grass emerging from a long winter.

Now, imagine the sudden onset of crushing pain across your rib cage, shortness of breath, and a cold sweat across your face and back. A beautiful spring day, interrupted by the classic symptoms of a heart attack!

If you don’t want this to happen to you, prevention is critical, and an important part of an over-all prevention strategy is to detect risk factors for heart disease early in the course of the disease. Although the symptoms of an acute heart attack may appear suddenly, the underlying disease (called coronary atherosclerosis) that ultimately results in a heart attack occurs over many years.

Heart disease is the leading cause of death in the United States, and about every 25 seconds one of us will suffer a heart attack.  Annual blood testing plays an important role in helping to identify risk factors early in the course of vascular disease. Regrettably, many doctors are not aware of several blood tests that offer great benefit at detecting cardiac risk factors beyond those detected with typical, routine testing. At your next physical, be sure to take this list of seven lifesaving blood tests with you so that you and your doctor can help identify heart disease risk factors early, rather than too late. 

1. HbA1c

Elevated blood sugar is a significant risk factor for heart disease, even if you don’t have diabetes. Routine testing usually includes a fasting blood sugar level, but a far more accurate measurement of your blood sugar control over a three-month period of time is the hemoglobin A1c (HbA1c) test. This test is usually given only to diabetics, yet all of us need to fully understand the risks associated with high blood sugar.  If your HbA1c level is not optimal (over 5.7), you need to achieve better control over your blood sugar levels. Weight loss, exercise, and diet are three time-proven strategies of achieving better blood sugar control. Nutrients like cinnamon, soluble fiber, and the exotic-sounding Indian Ayurvedic herbal medicine Gymnema sylvestre can help, too.

2. Fibrinogen

Increasingly, scientists have discovered that inflammation plays a deadly role in most degenerative diseases.  Fibrinogen levels increase in response to inflammation in our body.  Recent studies suggest that elevated fibrinogen levels are an independent risk factor for heart disease and stroke in patients with decreased vascular circulation (peripheral artery disease).  If your fibrinogen levels are elevated, weight loss and physical activity can help. Also, consider fish oil, niacin, and folic acid, in addition to vitamins A and C, to support healthy fibrinogen levels.

3. Homocysteine

Elevated levels of homocysteine are associated with an increased risk of heart attack, stroke, bone fracture risk, and cognitive function including depression.  If your blood tests reveal elevated homocysteine levels, B-vitamins like folic acid, B12, and B6 can help support healthy homocysteine metabolism.

4. C-reactive protein

Elevated levels of C-reactive protein indicate your body is under assault from inflammation. This important test can help you ward off some of the most lethal diseases before they begin.  Studies suggest that C-reactive protein is a risk factor for a host of diseases including cardiac disease, macular degeneration and arthritic conditions.  For those with elevated CRP, a low dose of daily aspirin can be helpful.  Also, natural therapies like fish oil, L-carnitine, and soluble fiber can help support healthy levels of C-reactive protein.

5. TSH

Our thyroid gland is the master metabolic regulator of our key body functions.  Signs and symptoms of a significantly overactive or underactive thyroid are easy to recognize for most physicians. Studies show that mild thyroid disease can increase the levels of cholesterol in the blood, contribute to weight gain, and increase the risk of heart rhythm disturbances.  A screening test for thyroid stimulating hormone (TSH) starting at age 35, and every five years thereafter, is a good strategy to identify subtle thyroid malfunction early.

6. 25-hydroxy vitamin D

The remarkable benefits of vitamin D extend across the entire health spectrum. Produced in the skin during exposure to sunlight in the ultraviolet-B spectrum, vitamin D is also available as a low-cost dietary supplement (vitamin D3, cholecalciferol). Over thirty different cell types, including bone, vascular, brain, muscle, and immune system cells contain receptors for activated vitamin D. Recent scientific studies show that low levels of vitamin D are associated with an increased risk of certain types of cancer (e.g. breast, prostate), cardiovascular disease, and even the flu. Despite the enormous health benefits associated with optimal vitamin D status, the vast majority of us are insufficient, with some research suggesting as much as 80% of the population may not have optimal blood serum levels. A simple blood test can detect your vitamin D status. If you avoid sun exposure out of concern over skin cancer and premature skin aging, the latest research suggests that you will need somewhere between 2,000-8,000 IU of supplemental vitamin D3 daily to achieve optimal serum levels.

7. Advanced lipoprotein profiling

The information you obtain with advanced lipoprotein testing provides a wealth of detail on important parameters of heart disease risk, much more than the standard cholesterol profile.  For example, we know that small, dense LDL-cholesterol particles are far more plaque-producing than large, fluffy LDL-cholesterol particles. A standard cholesterol test does not differentiate between small, dense LDL and fluffy, buoyant LDL. Another example is the so-called “good” cholesterol, HDL. Standard cholesterol tests do not tell us if you have more of the favorable HDL2 subclass of particles or the less favorable HDL3, while advanced lipoprotein tests evaluate for HDL2 and HDL3 cholesterol. Several different types of advanced lipoprotein tests are available based upon your individual needs.

Stress, Immortality, and the Hormesis Hypothesis

Stress, Immortality, and the Hormesis Hypothesis

By Steven V. Joyal, MD

Stress, Immortality, and the Hormesis HypothesisIs low-level stress the secret to immortality?

Longevity scientists have long been puzzled by the fact that stress, when carefully applied, very often results in prolongation of lifespan rather than causing premature death.

We need to be careful by the manner in which we characterize or define stress in the context of lifespan extension. Stress, as a critical causal factor in lifespan extension, is best defined by the term hormesis. When stress, either internal or external, is applied to a living system at a relatively low level so that a beneficial biological adaptation occurs, we define this as hormesis. The capacity of a biological system to adapt and thrive in response to stress is critical to survival. In fact, aging itself can be characterized as the inability to adapt and respond successfully to stress.

We must differentiate chronic stress that overwhelms a biological system and results in damage and decay from the type of low-level stress of hormesis that contributes to a beneficial biological response. For example, chronic stress that causes large bursts of the hormones cortisol and “fight or flight” catecholamines like adrenaline accelerates the aging process and reduces lifespan. In contrast, low-dose radiation with gamma rays and beta radiation has been shown in several studies to stimulate natural chemical and biological processes that are actually protective against cancer.1-4 This may seem surprising to some, but low-level gamma radiation, rather than causing cancer and premature death, has been shown to suppress cancer induction from chemical carcinogens, oncogenic retroviruses, and viral oncogenes like ras and src.5,6

Significant lifespan extension as a result of calorie restriction is probably the best evidence in support of the hormesis hypothesis as applied to longevity. Animals that are calorie restricted are able to significantly suppress chemical and radiation-induced cancers as opposed to peer controls fed ad libitum. Calorie restriction in animals results in an increase in resistance to oxidative stress and the negative effects of excess inflammation as well as the deleterious impact of exhaustive physical exercise.

The beneficial biological response to oxidative stress in calorie restriction is particularly impressive. Animals under calorie restriction have reduced levels of oxidatively damaged proteins, lipids, and DNA. Calorie restricted animals have an amazing capacity to beneficially modify gene expression involved in glucose metabolism, protein synthesis, and cellular energy capacity. Gene expression in calorie restricted animals shows adaptations involving enhancement of detoxification, anti-inflammatory pathways, and DNA repair enzymes.

Do the impressive adaptive benefits of calorie restriction share a common pathway?

The hormesis hypothesis helps provide an answer.

The mild stress of calorie restriction rapidly turns on a variety of gene pathways critical for essential defense and survival of the organism. Gene expression studies show that calorie restricted animals rapidly turn on genes related to stress response and energy metabolism. For example, Lee et al showed that of 6,437 genes activated by calorie restriction, nearly 30% were related to energy metabolism and stress response.7 Hormesis as an explanation for the biological benefits of calorie restriction implies an adaptive mechanism through evolutionary biology. In order to survive, living systems must adapt to an ever-changing barrage of internal and external insults. The low-level stress of calorie restriction produces gene expression changes that create a variety of positive adaptive responses for longevity.

In addition to calorie restriction, other strategies may help mimic the hormetic response. Consistent, mild-to-moderate (never exhaustive) exercise triggers a variety of adaptive mechanisms similar to calorie restriction. Exercise adaptation includes improvements in insulin signaling, mitochondrial energy metabolism, and resistance to oxidative stress, all of which are also known to occur with calorie restriction.

Nutrients, too, have hormetic properties. One example is vitamin D. The past decade has seen a veritable explosion of research supporting beneficial biological roles for vitamin D in the immune system, cardiovascular system, central nervous system, and endocrine system, in addition to control of the cell cycle and cancer pathogenesis.8 There is compelling evidence that vitamin D acts as a hormetic agent. Low doses of vitamin D exert stimulatory effects upon wound healing, while large doses may inhibit psoriatic plaque. A longitudinal, nested, case-control study of prostate cancer showed that both low (</=19 nmol/l) and high (>/=80 nmol/l) 25(OH)-vitamin D serum concentrations were associated with higher prostate cancer risk, while serum concentrations of 25(OH)-vitamin D within the 40-60 nmol/l range comprised the lowest risk of prostate cancer.9 A biphasic, U-shaped response curve is a characteristic of hormesis.

Clearly, more research is needed to understand how best to evaluate the hormesis hypothesis as applied to calorie restriction, physical exercise, and nutrients like vitamin D in the context of longevity science. In the interim, we are left with the intriguing possibility that stress, when applied carefully and strategically, may be the key to living healthier, longer.

References:

  1. Mitchel REJ. Low doses of radiation are protective in vitro and in vivo: Evolutionary origins. Dose-response. 2006;4(2):75–90.
  2. Mitchel REJ. Low doses of radiation reduce risk in vivo. Dose-Response. 2007;5(1):1–10.
  3. Sakai K, Nomura T, Ina Y. Enhancement of bio-protective functions by low dose/dose-rate radiation. Dose-Response. 2006;4(4):327–332.
  4. Sakai K, Hoshi Y, Nomura T, Oda T, Iwasaki T, Fujita K, Yamada T, Tanooka H. Suppression of carcinogenic process in mice by chronic low dose rate gamma-irradiation. Int J Low Radiat. 2003;1(1):142–146.
  5. Bauer G. Low dose radiation and intercellular induction of apoptosis: potential implications for control of oncogenesis. Int J Radiat Biol. 2007;83(11–12):873–888.
  6. Jürgensmeier JM, Schmitt CP, Viesel E, Höfler P, Bauer G. Transforming growth factor beta treated normal fibroblast eliminate transformed fibroblasts by induction of apoptosis. Cancer Res. 1994;54(2):393–398.
  7. Lee CK, Klopp RG, Weindruch R, Prolla TA. Gene expression profile of aging and its retardation by caloric restriction. Science. 1999;285(5432):1390-3.
  8. Norman AW. From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. Am J Clin Nutr. 2008;88(2):491S-499S.
  9. Tuohimaa P, Tenkanen L, Ahonen M, Lumme S, Jellum E, Hallmans G, Stattin P, Harvei S, Hakulinen T, Luostarinen T, Dillner J, Lehtinen M, Hakama M. Both high and low levels of blood vitamin D are associated with a higher prostate cancer risk: a longitudinal, nested case-control study in the Nordic countries. Int J Cancer. 2004;108(1):104-8.

How to maintain healthy blood sugar with four supplements

How to  maintain healthy blood sugar with four supplements
Dietary intervention targets the underlying causes of high blood sugar and is a key step towards protecting yourself against the damaging effects caused by high blood sugar.

1. Apple Cider Vinegar

Apple cider vinegar combats blood sugar spikes after meals. Minimizing sugar spikes helps to restore insulin sensitivity…the hallmark of type 2 diabetes.

One study by Italian researchers showed that when healthy subjects consumed 4 teaspoons of apple cider vinegar with a meal, there was a 30 percent reduction in their glycemic response, or rise in blood sugar. Reducing your glycemic response is essential for beating diabetes.

2. Lipoic Acid

Glucose (blood sugar) destroys insulin receptors. Without the receptors, insulin can not work. Lipoic acid is a naturally occurring antioxidant that protects insulin receptors.

Recently, researchers revealed dramatic effects in improving insulin sensitivity in overweight adults suffering from type 2 diabetes. The antioxidant produced significant improvements in just four weeks.

Lipoic acid is also effective in treating diabetic neuropathy, which is characterized by numbness, tingling, and pain in the extremities. A large, randomized, placebo-controlled, multicenter, double-blind study involving 328 patients with type-2 diabetes revealed that it significantly improved symptoms.

Life Extension suggests taking 200 to 300 mg/day of R-lipoic acid (the “R” form is more potent).

3. Coenzyme Q10

Coenzyme Q10 (CoQ10) is a potent antioxidant that reduces oxidative stress. Diabetics experience a high degree of oxidation that causes cellular damage.

CoQ10 is required to convert fats and sugars into cellular energy. Yet, the natural production of CoQ10 declines in diabetics. The best form of CoQ10 to supplement with is called ubiquinol. This form is easily absorbed and significantly increases blood levels.

Life Extension suggests taking 200 mg/day of ubiquinol CoQ10.

4. Pyridoxamine

The pyridoxamine form of vitamin B6 protects the body’s proteins from glycation. Sugar (glucose) in the blood can bind to proteins, particularly when blood levels are high. This binding causes the formation of dysfunctional proteins, which accumulate with time and contribute to some of the signs of aging.

Scientific research suggests that if you want to help protect your body against glycation, nutrients that help prevent the formation of AGEs may be beneficial. The latest information shows that pyridoxamine may also be of significant help in preventing the formation of these aging molecules.

In fact, one prominent antiaging doctor described pyridoxamine as “the most potent natural substance for inhibiting AGE formation.” By preventing AGE formation and working as a coenzyme in chemical reactions, pyridoxamine can support healthy nerve, eye, cardiovascular and kidney function.

Life Extension suggests taking 50 mg/day of pyridoxamine.

Men should not stop using Avodart because of heart attack fears! Life Extension’s Rebuttle

Life Extension’s rebuttal by William Faloon in reference to published clinical study in Thursday’s New England Journal of Medicine on Avodart and increased risk for sudden myocardial infarction.

I suspect none of the study participants where using testosterone creams, even though they were ALL likely to be testosterone deficient. You will soon read the findings of an internal study we did on Life Extension Foundation members that found 86% of men have less than optimal testosterone levels.

The significance of this is that testosterone deficiency predisposes a man to heart failure. By taking a drug like Avodart when in a testosterone deficient state, the heart muscle will be robbed completely of this vital anabolic hormone. That may be why this study showed higher heart failure rates in the Avodart group.

 Those with prostate cancer often intentionally suppress their testosterone levels and have to be extra vigilant in protecting against heart attack. Log on to http://www.lef.org/magazine/mag2009/mag2009_05.htm for information on how to protect against multiple risk factors underlying coronary atherosclerosis.

 Aging men (without prostate cancer) should do whatever is necessary to maintain free testosterone blood levels of 20-25 pg/mL, while keeping DHT blood levels at the very low end of the reference range.

This provides the heart, brain and other vital parts their testosterone requirements while protecting the prostate gland against the adverse effects of excess DHT.

 The Avodart study exposes the flaws in so many of these single agent trials. We know, for example, that 25-hydroxyvitamin D serum levels strongly predict prostate cancer risk. If this potent confounding factor was not accounted for, then the results shown with Avodart have little meaning.

If, for example the placebo group’s median 25-hydoxyvitamin D level was 35 ng/mL, and the Avodart group was only 25 ng/mL, this would skew the results in a way to show Avodart less effective than it may really be. Dietary intakes of cruciferous vegetables would have an equally significant confounding effect.

 Bill Faloon