Carbohydrates Drive Up Cholesterol

Evil ToastOctober 16th, 2009 – Despite what your doctor and favorite fitness magazine tell you, dietary cholesterol is not the enemy. In fact, our own cells manufacture roughly 80% of the cholesterol in our body (1). Increase your dietary intake, and normally the body will compensate by producing less of its own. Decrease, and your body will make more.

So where do carbohydrates fit in to all of this?

When you ingest carbohydrates, they are broken down into glucose and released into the blood stream. This raises blood sugar levels, and the body releases insulin to deliver the sugar to the various cells in the body for use as fuel. Aside from storing nutrients in the body, insulin also stimulates the enzyme HMG-CoA reductase, which determines the rate and amount of cholesterol produced by our cells. (2) The more cholesterol our cells produce, the less they remove from the LDL particles in the blood, and the more cholesterol remains in circulation.

Take home message – It’s the toast, not the eggs.

References

1. Protein Power
Dr. Michael Eades
New York, NY: Creative Paradox LLC (2000)

2. Interaction between cholesterol and glucose metabolism during dietarycarbohydrate modification in subjects with the metabolic syndrome
Maarit Hallikainen, et al.
Am. J. Clinical Nutrition, Dec 2006; 84: 1385 – 1392.

Benefits of Yoga

When guys hear the word yoga they think hippies, tofu, and small muscles.

Contrary to the popular belief that yoga is only for women, it was traditionally practiced by men although it has not maintained its male student population since its arrival in the Western world. Only a small percentage of the 15 million people who practice yoga are men. (1)

What men don’t realize is that most women consider it incredibly sexy when a guy practices yoga. I imagine this probably has something to do with the fact that most males who practice yoga [and lift weights] exude incredible confidence, self-security and a strong posture.

Aside from improving your sex appeal, our primary focus in this article is to show that any guy, whether you may be a bodybuilder, endurance athlete, or strength athlete, can benefit from this ancient practice. You will find that yoga can be an amazingly powerful tool in enhancing fat loss, overall athleticism, and injury prevention and rehabilitation.

Fat loss & Cardiovascular –

One key benefit of yoga over traditional forms of “cardio” or supplemental “calorie burning” exercises is the actual pleasure found in practicing it. Compared to the boring and dreaded treadmill or stair machine, yoga is often considerably more engaging and enjoyable, yet just as beneficial. Plus, yoga is something that can be practiced from home, in the comfort of one’s living room.

Lack of steady commitment is one of the biggest factors in why ‘weight loss’ or ‘fat loss’ programs fail. One following a steady yoga practice may almost feel like they reach their goals faster and easier simply due to the fact that the exercise is enjoyed. It’s interesting to note that the positive physical effects almost start to seem secondary after one realizes the positive psychological effects. Either way, it’s a catalyst for success.

Warrior One

Philosophies on the actual cardiovascular benefits of yoga are vast and vary greatly depending on the type of yoga practiced. Most would agree that more vigorous activity such as running, field sports, or circuit training will provide stronger cardiovascular stimulus. However, research has shown yoga to be beneficial for improving lipid profiles, insulin resistance and cardiovascular risk factors. (5) Part of the benefits can be attributed to the stress and anxiety relief alone, which can reduce heart disease risk and high blood pressure.

Flexibility & Circulatory-

The most commonly known benefit of yoga is increased flexibility, which can offer potential benefits for strengthening and balancing muscle and connective tissue.

Most of us understand that when the muscles are strengthened during weight training they are in turn pulled tighter. However, this ‘tightness’ can disable your muscles and connective tissue from properly relaxing when they should be. This relaxation is especially important for the opposing muscle in any given movement. (eg, the biceps should relax during a bench press) Mechanical musculoskeletal movement can be highly compromised and susceptible to injury by overly tightened muscles.

What about old fashioned stretching?

The most significant benefit you will find with yoga over traditional stretching is the light and progressively increasing warm-up like activity and increased blood circulation. Most other forms of stretching totally neglect a sufficient warm up period and only stretch isolated muscles groups. Poses performed in yoga encourage you to support your own body weight, which engages more muscle groups and promotes rapid engorgement of blood in the muscle belly from the resistance. More blood in the muscle means more effective stretching.

Side Angle Pose

From a recovery standpoint, increased systemic blood flow will promote nutrient delivery and toxin clearance. This of course translates into faster repair and increased muscle hypertrophy when combined with the proper weight training program. The enhanced circulation will also greatly improve injury rehabilitation. Even serious injuries with the anterior cruciate ligament (ACL) or the rotator cuff can also be improved with physical therapy, supplemented with yoga.

An integral part of yoga is the seamless transition from one pose to the next. For instance, the controlled movement and twisting of the spine provides significant benefit for the smaller stabilizer muscles controlling the vertebrae (eg, rodatores, multifidus, interspinales, and intertransversarii). Typical back extensions, lat pulls and upright rows will help these muscles very little, if at all. A recent ACE study showed that an hour of yoga three times per week increases average trunk flexibility by 13% in only eight weeks.

Remember, flexibility does not happen overnight. If connective tissue is “stretched” it is considered an injury, so be patient. The lengthening of the muscle and fascia must happen together through months of progressive training.

Balance –

When the word “balance” is used there tends to be two thoughts that come to mind, balance in reference to symmetry and balance in reference to being able to stabilize the body. Yoga helps improve both types of balance. This is achieved in yoga because all poses are done on all sides of the body. Poses are done from side to side and front to back. When working the whole body in the equal amounts, the whole body responds as a whole and becomes balanced.

When the body becomes “balanced” it becomes realigned. All of the 200 plus bones in the body are held in alignment by your muscles and connective tissue. As discussed earlier, if one (or a group) of muscles are tighter than the opposing muscle it can cause imbalance and potentially lead to discomfort or injury. With overall enhanced flexibility you will find balance, and the benefits herein will lead to improved posture, movement and flow. Common physiological ailments can often be improved by simply increasing overall flexibility and balance. (Eg, shin splints, plantar fasciaitis, anterior compartment syndrome, meniscus degeneration, and various tendonitis related issues.) In fact, research has shown yoga can improve repetitive-stress related injuries like carpal tunnel syndrome, (3) while also helping with inflammation related conditions, such as rheumatoid arthritis. (2)

Breathing –

Yoga can improve breathing capacity by improving the flexibility of the rib cage, shoulders and diaphragm. (4) Improved flexibility in these areas will aid in the proper involvement of the diaphragm and the abdominal muscles in the act of breathing instead of only using your upper chest. This increases the amount of air taken into the lungs.

Oxygenation efficiency can be improved by focused and controlled breathing. (4) In yoga, each pose is coordinated with your breathing which will improve your mind-to-body awareness, power of concentration, and the body’s ability to replace carbon dioxide with oxygen.

Endurance –

There are two basic types of exercise; isokinetic and isometric. Isokinetic exercise involves strength in a repetitive movement (curls, bench, squats, ect.). Isometric exercise involves the tensile strength without movement (holding a pose under load). A study done at UC Davis demonstrated that isometric exercise increased muscle endurance by as much as 57% while isokinetic exercise increased muscle endurance by only 28%. The same study showed that isometric exercise provided remarkable improvements in flexibility and oxygen intake. This increased endurance is good news for virtually any athlete, minus those exclusive to explosive strength. (Discus thrower, linemen, sprinter, ect) Just be sure to choose the correct style of yoga for your goals.

Lifting the spirit –

During an intense yoga session its often encouraged to find the connection between the instructions of the mind and the order of the body. It is this metaphysical interplay between these elements that keep the individual constantly engaged and challenged.

As you attempt to hold a rigorously demanding pose you may ask yourself –

“Am I consciously in control?”

“Can I consciously work through the uncomfortable burning sensation?”

“Can I strengthen the signal from mind to muscle?”

The act of mindfully focusing on your body and its functions while performing a difficult pose in yoga gives the mind permission to focus on the task at hand, rather than stress inducing factors.

As you practice yoga, you will find that it brings a certain feeling of clarity, order and mindfulness – and an ability to conquer stress. Learning to apply this skill set to everyday tasks will enhance your productivity and overall fulfillment – whether it is a verbal presentation, a cage fight or simply falling asleep. (6-8)

cross legged

References

1. (Seattle times article” Yoga Poises for Chain Pose” Published Tuesday Sept. 21, 2004)

2. Measuring the Effects of Yoga in Rheumatoid Arthritis I. HASLOCK, R. MONRO, R. NAGARATHANA, H. R. NAGENDRA, and N. V. RAGURAM Rheumatology, Aug 1994; 33: 787 – 790.

3. Yoga-Based Intervention for Carpal Tunnel Syndrome: A Randomized Trial Marian S. Garfinkel, Atul Singhal, Warren A. Katz, David A. Allan, Rosemary Reshetar, and H. Ralph Schumacher, Jr JAMA, Nov 1998; 280: 1601.

4. Pattern of breathing and ventilatory response to CO2 in subjects practicing hatha-yoga

D. C. Stanescu, B. Nemery, C. Veriter, and C. Marechal J Appl Physiol, Dec 1981; 51: 1625.

5. Risk Indices Associated with the Insulin Resistance Syndrome, Cardiovascular Disease, and Possible Protection with Yoga: A Systematic Review

Kim E. Innes, Cheryl Bourguignon, and Ann Gill Taylor
J Am Board Fam Pract, Nov 2005; 18: 491 – 519.

6. Sahaja Yoga Meditation as a Family Treatment Programme for Children with Attention Deficit-Hyperactivity Disorder Linda J. Harrison, Ramesh Manocha, and Katya Rubia Clinical Child Psychology and Psychiatry, Oct 2004; 9: 479 – 497.

7. The effects of yoga on the attention and behavior of boys with Attention Deficit/hyperactivity Disorder (ADHD) Pauline. S. Jensen and Dianna T. Kenny

J Atten Disord, May 2004; 7: 205 – 216.

8. Yoga for anxiety: a systematic review of the research evidence • Commentary

G Kirkwood, H Rampes, V Tuffrey, J Richardson, K Pilkington, and S Ramaratnam
Br. J. Sports Med., Dec 2005; 39: 884 – 891.

Other Primary Resources

Uniting body, mind, spirit: Nicole Joseph AAP News, Dec 2004; 25: 320.

Real Men Do Yoga by John Capouya

Yoga: a Yoga Journal Book.

Resveratrol for prevention in human prostate cancer

Grapes - a greate source of resveratrolOctober 14th, 2009 – With over a decade of test tube and animal research behind resveratrolís anti-cancer benefits, it finally appears that researchers are ready to take the fast track to human clinical trials in cancer prevention and therapy. (1)

Resveratrol is abundantly found in nature in various fruits, nuts and other plants and accounts for 5 to 10% of the biomass in grape skin. (2) Over the years, resveratrol has demonstrated multiple inhibitory actions on the three stages of cancer including initiation, promotion and progression. (1-3) Part of resveratrols action in preventing initiation of cancer is from its potent anti-oxidant effect and ability to scavenge free radicals. Promotion of tumor growth appears to be inhibited by Resveratrol’s ability to exert anti-inflammatory activity through inhibition of cyclooxygenases (COX-1 and COX-2).

Resveratrol also inhibits cancer cell growth by antagonizing the action of androgens at the androgen receptor (AR) in prostate cancer cells. Whether this anti-androgenic effect of resveratrol has effects on AR in muscle, fat or mammary tissue remains to be seen.

-Eric Potratz
Founder & President


References

1. CancerPrevention and Treatment withResveratrol: From Rodent Studies to Clinical Trials
Anupam Bishayee
CancerPrevention Research,May 2009; 2: 409 – 418

2. Resveratrol: A Candidate Nutritional Substance for Prostate
Cancer Prevention
Jubilee R et al.
J Nutr.2003 Jul;133(7 Suppl):2440S-2443S

3. Resveratrol inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells.
Mitchell, S. H. et al.
Cancer Res. 59: 5892-5895. (1999)

Resveratrol better than Viagra?

Resveratrol Better Than Viagra

October 14th, 2009 – Drugs like Viagra (Sildenafil citrate) and Cialis (Tadalafil) are used to treat erectile dysfunction (ED) by increasing blood flow to the erectile tissue in the penis known as the corpus cavernosum.

These drugs increase blood flow to erectile tissue by inhibiting the phosphodiesterase enzymes (PDE5 & 6), which prolongs the action of cGMP in the smooth muscle tissue, increasing the dilation response from nitric oxide (NO) release. However, inhibition of the phosphodiesterase enzyme system has effects across the entire body and can lead to side-effects including headache, skin flushing, nasal congestion and muscle aches. (1) These are very unwelcome side-effects when trying to stimulate sexual arousal.

New research suggests that resveratrol can also trigger erections by promoting blood flow to the erectile tissue in the penis. (2) This vasodilatory effect appears to occur within minutes of resveratrol exposure, suggesting that supplementation may provide a quick temporary boost in sexual performance. (3)

Evidence suggests that resveratrol does not have the side-effects typically associated with popular ED drugs. Resveratrol improves vasodilation by multiple cellular mechanisms, and does not negatively inhibit the phosphodiesterase enzyme system, which can lead to unwanted side-effects. (3) Whether or not resveratrol is a worthy substitute to powerful prescription drugs such as Viagra and Cialis remains to be determined.

-Eric Potratz
Founder & President


References

1. [Sildenafil (Viagra) in erectile dysfunction. Effective treatment with noteworthy side effects]
C Rolf and E Nieschlag
Dtsch Med Wochenschr, Nov 1998; 123(45): 1356-61.

2. trans-Resveratrol relaxes the corpus cavernosum ex vivo and enhances testosterone levels and sperm quality in vivo.
Shin S, Jeon JH, Park D, Jang MJ, Choi JH, Choi BH, Joo SS, Nahm SS, Kim JC, Kim YB.
Arch Pharm Res. 2008 Jan;31(1):83-7.

2. Resveratrol, a component of red wine, elicits dilation of isolated porcine retinal arterioles: role of nitric oxide and potassium channels.
Nagaoka T, Hein TW, Yoshida A, Kuo L.
Invest Ophthalmol Vis Sci. 2007 Sep;48(9):4232-9.

Hawthorn Berry in Treating High Blood Pressure

Hawthorn berryOctober 14th, 2009 – Hawthorn berry (Crateagus oxycanthus) is used as an herbal supplement to help improve the functioning of the cardiovascular system, and has shown a unique function in lowering blood pressure in hypertensive subjects.

A collaboration of several different studies involving 855 patients using hawthorn extract, in addition to conventional treatments for chronic heart failure, show increased exercise ability, lower oxygen consumption by the heart, and less fatigue. (1) In another trial, 92 men and women, all with mild hypertension, were given hawthorn extract or a placebo three times a day for three months. The individuals receiving the extract had a significant decrease in both systolic and diastolic blood pressure at the end of the three months when compared to the placebo group. (2)

The active compounds found in hawthorn responsible for this drop in blood pressure are procyanidins and flavonoids (specifically hyperoside). (3) Procyanidins found in hawthorn help increase nitric oxide (NO) release to stimulate NO mediated vaso-relaxation in the endothelial walls of blood vessels. (2) The NO molecules diffuse into vascular smooth muscle cells (VSMC), leading to a series of chemical reactions that eventually increase the vasodilation of such cells. (2) Hyperoside is the flavonoid in hawthorn that contributes to the functionality of procyanidins by destroying the free radicals that would otherwise disrupt the activity of NO. (1) Contrary to what might be expected from a supplement used to treat hypertension, hawthorn has actually been observed to have beneficial effects for people with hypotension. (5) One study found that an herbal drug, of which its main component was liquid hawthorn berry extract, actually increased the systolic blood pressure of orthostatic hypotensive patients twice as much as that of the control group. (6)

-Dylan Udy


References

1. Center for the Advancement of Health.
“Herbal Remedy, Hawthorn Extract, Can Help The Heart, Review Finds.”
ScienceDaily 23 January 2008. 11 July 2009

2. Anti-hypertensive Nutraceuticals and Functional Foods
Chen, Zhen-Yu et al.
Journal of Agricultural and Food Chemistry 2009 57 (11), 4485-4499

3. Plants and hypotensive, antiatheromatous and coronarodilatating action
Petkov V.
Am J Chin Med 1979; 7(3): 197

4. Crataegus Special Extract WS 1442 Induces an Endothelium-Dependent, NO-mediated Vasorelaxation via eNOS-Phosphorylation at Serine 1177
Brixius, Klara et al.
Cardiovascular Drugs Therapy (2006) 20: 177-184

5. Ayurvedic & Herbal Health Medicine. ìHawthorn Berry from Bioforce.î
11 July 2009

6. Efficacy and safety of a herbal drug containing hawthorn berries and D-camphor in hypotension and orthostatic circulatory disorders/results of a retrospective epidemiologic cohort study.
Hempel B., et al.
Arzneimittelforschung, 55(8), 443-50. (2005)

Sunlight Increases Testosterone Production

Sunlight Increases Testosterone

October 14th, 2009 – Interested in boosting your testosterone levels? Try Sunlight.

Research shows that testosterone levels are highest in men during the summer months of June though July. (1) In a study involving men between the ages of 19-30, researchers found that only 1 hour of sunlight exposure stimulated luteinizing hormone (LH) production by 69.5% (2) luteinizing hormone is the primary hormone that signals the testes to increase testosterone production.

Sunlight exposure is also the main source of vitamin D production in the body, and low vitamin D levels are a good indicator of insufficient sunlight exposure. Therefore, testing for vitamin D can be an excellent way to ensure you are getting enough sunlight for optimal testosterone levels.

The take home message – Get outside as much as possible!

-Eric Potratz
Founder & President


References

1. Variation in Levels of Serum Inhibin B, Testosterone, Estradiol, Luteinizing Hormone, Follicle-Stimulating Hormone, and Sex Hormone-Binding Globulin in Monthly Samples from Healthy Men during a 17-Month Period: Possible Effects of Seasons
Anna-Maria Andersson, et al
J. Clin. Endocrinol. Metab., Feb 2003; 88: 932 – 937.

2. Luteinizing hormone following light exposure in healthy young men
IY Yoon, et al.
Neurosci Lett, April 24, 2003; 341(1): 25-8

7,8-Benzoflavone Carcinogenic?

7,8-benzoflavone October 14th, 2009 – A search on Google for 7,8-benzoflavone yields a link to a blogger who appears to have the opinion that 7,8-benzoflavone is a dangerous carcinogenic substance. They based this opinion on several studies which combined high levels of well known cancer causing substances, with 7,8-benzoflavone. They provided no references showing 7,8-benzoflavone is a carcinogenic substance in and of itself.

The first reference discusses the carcinogenbenzo[a]pyreneas being highly carcinogenic and that when combined with 7,8-benzoflavone, this can increase the rate of tumor formation. While this is true, this particular study foundzero tumor formation when 7,8-benzoflavone was used alone, and it in fact inhibited tumor formation caused by the more potent carcinogen7,12-dimethylbenz(a)anthracene(DMBA), thus offering a net protective effect against tumor formation. (1)

Other studies have also shown 7,8-benzoflavone has protective effects against cancer by inducing 2-hydroxylation of estrogens, thus increasing the clearance of estrogens and reducing cancer risk. (2-4)

Isolating flavonoids and carcinogens together in an in-vitro environment is a popular cancer research practice for studying the metabolism of cancer causing substances. Virtually all natural flavonoids (exp., quercetin, tangeretin, chrysin or nobiletin) have been found to negatively or positively metabolize carcinogenic chemicals in special test tube environments. However the research clearly shows a net anti-cancer effect from naturally occurring flavones. (5-7)

-Eric Potratz
Founder & President


References

1. Hydrocarbon Hydroxylase- and Polycyclic Hydrocarbon Tumorigenesis: Effect of the Enzyme Inhibitor 7,8-Benzoflavone on Tumorigenesis and Macromolecule Binding.
Nadao Kinoshita et al.
Proc Natl Acad Sci U S A. 1972 April; 69(4): 824-828

2. Modulation of rabbit and human hepatic cytochrome P-450-catalyzed steroid hydroxylations by alpha-naphthoflavone
GE Schwab, JL Raucy and EF Johnson
Volume 33, Issue 5, pp. 493-499, 05/01/1988

3. Regioselective 2-hydroxylation of 17beta-estradiol by rat cytochrome P4501B1.
M Rahman, C Hayes Sutter, GL Emmert, and TR Sutter
Toxicol Appl Pharmacol, November 1, 2006; 216(3): 469-78.

4. Naturally occurring coumarins inhibit 7,12-dimethylbenz[a]anthracene DNA adduct formation in mouse mammary gland
Misty Prince, Cheryl T. Campbell, Taylor A. Robertson, Amy J. Wells, and Heather E. Kleiner
Carcinogenesis, Jun 2006; 27: 1204 – 1213.

5. Dietary Flavonoids and the Risk of Colorectal Cancer
Evropi Theodoratou, et al.
Cancer Epidemiol. Biomarkers Prev., Apr 2007; 16: 684 – 693

6. Flavonoids and the Risk of Oral and Pharyngeal Cancer: A
Case-Control Study from Italy
Lagiou, et al.
Cancer Epidemiol. Biomarkers Prev., Aug 2007; 16: 1621 – 1625.

7. A Review of the Epidemiological Evidence on Tea, Flavonoids, and Lung Cancer
Ilja C. W. Arts
J. Nutr., Aug 2008; 138: 1561S – 1566S

Turmeric Curcuminoids Aiding in Arthritis Pain

Turmeric Root Against Arthritis Pain

October 14th, 2009 – Turmeric (Curcuma longa) is a plant and member of the ginger family, and among its most important functions is its anti-inflammatory effects in the treatment of arthritis. The main component of turmeric that contributes to these medicinal properties is a family of polyphenols known as curcuminoids. Of the curcuminoids, Curcumin (diferuloylmethane – Fig. 1) is the most notable, followed by demethoxycurcumin and bisdemethoxycurcumin. These constituents are found primarily in the rhizome (root) of the plant and are responsible for its anti-arthritic properties. (1)

Curcumin functions by inhibiting the transcription factors of a cell that turn on the genes coding for inflammatory proteins including cytokines and chemokines. (2) With the expression of these genes turned off, pain from rheumatoid arthritis can be greatly reduced or eliminated. Rheumatoid arthritis (RA) is an autoimmune disease that causes inflammation of joints and of the tissue around joints. (3)

In an experiment designed to discover the mechanism of turmeric’s medicinal effects in the treatment of RA, doctors at the University Of Arizona College Of Medicine conducted experiments with female rats after inducing arthritis. (4) The results showed that turmeric extract containing a high percentage of the curcuminoids have a dramatic effect on the prevention of joint inflammation and destruction. Specifically, inflammatory cell influx, joint levels of prostaglandin E2, and periarticular osteoclast formation were all significantly reduced when turmeric extract was injected intraperitoneally (into the abdomen). (4) Curcumin is well known as a molecule that can treat a plethora of health issues without the risk of any negative side effects. (5)

-Dylan Udy

References

1. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research.
Altern Med Rev. 2009 Jun;14(2):141-53

2. Turmeric Extracts Containing Curcuminoids Prevent Experimental Rheumatoid Arthritis.
JL Funk, et al.
J. Nat. Prod. 2006, 69, 351-355

3. Rheumatoid Arthritis (RA)
William C. et al
medicinenet.com/rheumatoid_arthritis/article.htm

4. Turmeric Extracts Containing Curcuminoids Prevent Experimental Rheumatoid Arthritis.
JL Funk, et al.
J. Nat. Prod. 2006, 69, 351-355

5. Role of curcumin in health and disease
Leelavinothan Pari; et al.
Archives Of Physiology And Biochemistry, 114, no. 2 (2008): 127-149

Transdermal Steroids – Expanded

If there is one topic that is misunderstood in the steroid community, it’s Transdermal Steroids (TS’s). The value of TS’s are under-estimated, and the science has been over looked by the vast majority. In this article, I intend to shed some light on TS’s and introduce a few new transdermal options that can offer benefits to athletes, bodybuilders and HRT patients alike.

As a developer of several transdermal products, and a counselor to a number of TRT patients; I’ve learned that a majority of men consider Androgel™ and Testim™ the only real viable topical hormones. This makes sense, being they are the most popular FDA approved testosterone gels currently available. However, there are more options to be considered. Steroid hormones such as nandrolone and boldenone offer useful advantages when delivered topically. Legal prohormones such as DHEA and pregnenolone can also offer great benefits when used topically (Found in Dermacrine). One benefit with all TS’s is their quick clearance from the body (generally less than 72hrs for most hormones). This is advantageous for PCT, when the quick clearance of hormones is desired (often a problem with long-acting injectable steroids which may take months to clear the system.)

Before we review some of the alternatives to testosterone gel, let’s take a quick look at some basic rules so we can have a better understanding of how we can manipulate the hormonal effects for our best interest.

Application site –

The site of application is one way to maximize the effectiveness of our topical hormones, while also altering the action the hormone has on the body. For instance, the skin on the front of the neck is thin and very vascular, making it ideal for systemic transdermal delivery. The skin on the shoulders and upper back – areas where you may have had acne as a teenager — are highly concentrated with steroidogenic enzymes such as 3b HSD and 17a HSD. These are the enzymes required to make hormonal conversions, such as DHEA > androstenediol > testosterone. On the flip side, the stomach area tends to carry a higher amount of the aromatase enzyme, especially if you’re prone to holding fat in the abdominal region. This would be an area to avoid applying testosterone gel, since the increased aromatase activity could increase the conversion to estrogen.

One area which can be advantageous to use for topical application is the scrotal skin. This area is extremely thin and easily penetrated by topical ingredients for systemic delivery. In fact, its absorption rate is about 4-5x more than anywhere else on the body. (1,2) This makes it the perfect spot for the delivery of topical ingredients, giving you more bank for the buck.

One thing to be aware of with scrotal applications is the higher conversion rate to DHT when applying testosterone to this area. There is heavier conversion to DHT because the scrotal skin carries a high concentration of the 5a-reductase enzyme. When the testosterone travels through the scrotal skin it interacts with the 5a-reductase enzyme and converts to DHT. This gives you a significant spike in DHT when you apply testosterone cream to your scrotum, which may or may not be a good thing. (see below for alternatives to testosterone and how to avoid the DHT)

An enlarged or irritated prostate is generally a symptom associated with high DHT. However, the DHT may not be entirely to blame. In fact, research has shown that topical DHT treatment can actually keep the prostate healthy and even reduce its size, as long as estrogen levels are also kept in control. (3,4) Plus, DHT is an antagonist of estrogen, so it’s going to help reduce gyno (male breasts) and water retention, while it also increase libido and erectile function. It could even be argued that DHT is more critical to a man’s well-being than testosterone.

Unfortunately, DHT can increase hair loss if you’re genetically prone to it, although this could be prevented if DHT levels are kept in range, bringing us to the next topic – the progesterone/DHT relationship. That’s right, progesterone can be healthy for a male too.

The word progesterone may sound frightening to some since it’s primarily known as a female hormone. However, it also offers health benefits for the male if used in very low and controlled amounts. You see, progesterone can naturally inhibit the conversion of testosterone to DHT thus helping to keep DHT in a healthy range (similar to finasteride albeit to a lesser degree). So how does this apply to real life?

Well, pregnenolone cream is legal and readily available in most counties, and as it passes the skin, pregnenolone readily interacts with the skins enzymes (3b HSD) and makes partial conversion to progesterone. (The reason for applying pregnenolone rather than strait progesterone is the added cognitive enhancements of pregnenolone.) In most cases, a 10-20mg application of pregnenolone cream would convert to sufficient amounts of progesterone to control DHT conversion from testosterone supplementation. (given via IM or topically)

If for whatever reason you don’t want to deal with combating DHT, or are extremely sensitive to its hair loss effects, you may want to consider using nandrolone or boldenone for topical application as alternatives to testosterone. If you’re lucky enough to have access to nandrolone or boldenone base powder, they are easily compounded into a topical and are perfect for transdermal delivery. These hormones are gentler on the hairline because they don’t convert to DHT. More specifically, when they interact with the 5a-reductase enzyme, they are converted to a less powerful 5a-reduced steroid, thus being ‘gentler’ than testosterone. Note: Nandrolone (Deca) can be a double edged sword given that it lacks a powerful 5a-reduced metabolite. It’s beneficial for preventing hair loss, but notorious for erectile dysfunction causes known as “Deca Dick”.

If you’re interested in staying legal and you don’t have access to AAS’s such as testosterone, nandrolone or boldenone, then DHEA is an excellent legal alternative, especially when used as a transdermal. When taken as a transdermal, DHEA is absorbed about 10x better than when taken orally. (5) Plus there is the additional benefit of increased metabolic conversion of hormones when they are taken through the skin. (6) As mentioned earlier, the shoulder and upper back skin have the highest concentration of enzymes required to make hormonal conversions (3b HSD & 17b HSD). Since DHEA is an immediate precursor to several anabolic hormones, the topical application of DHEA can cause a sharp rise in androstenediol, androstenedione and testosterone within a few hours of application. (These are the primary hormones that make Dermacrine so effective)

Remember, no matter what hormones you choose, be aware of moderation and balance.

 

References

1. Hypogonadal impotence treated by transdermal testosterone.
McClure RD et al. Urology 1991;37:224-8.

2. Testoderm TTS, Testoderm, and Testoderm with
adhesive [package inserts]. Mountain View, Calif: Alza Pharmaceuticals, 1998.

3. Percutaneous dihydrotestosterone (DHT) treatment. In: Nieschlag E, Behre HM, eds. Testosterone: action, deficiency substitution.
Schaison G, et al Berlin: Springer Verlag; 155-164. (1990)

4. Transdermal dihydrotestosterone and treatment of “andropause”.
de Lignieres B. Ann Med 1993;25: 235-41.

5. High bioavailability of dehydroepiandrosterone administered percutaneously in the rat C Labrie, M Flamand, A Belanger, et al. Endocrinol., Sep 1996; 150: S107 – S118.

6. The in vitro metabolism of dehydroepiandrosterone in human skin.
I Faredin, et al. Med Acad Sci Hung, Jan 1967; 23(2): 169-79.

Clomid & Nolvadex – The Dark Side

Preface – Over the past 15 years, the use of Clomid and Nolvadex, as Selective Estrogen Receptor Modulators (SERMs) has become a staple in the Hormone Replacement Therapy (HRT) and bodybuilding communities.

The popularity of these drugs stems from the popular advice to use these drugs for everything from testosterone recovery, bloat reduction, to gyno prevention. In many communities SERMs have become akin to vitamins — vitamins that can do no wrong and provide seemingly endless benefits.

This article is not intended to examine the proper use or possible applications of Clomid or Nolvadex. Instead, we will be exploring the historical development of these drugs, the short-term side-effects and long-term consequences.

As I will illustrate, these drugs are truly dangerous to men’s health.

Synthetic estrogens, the beginning –

It was the 1930s and there was a new age of hormone-dependant pathologies on the rise. Scientists were eager to determine the structural requirements of estrogen for new drug design.Diphenylethane

In 1937 Sir Charles Dodd of the Middlesex Hospital of London found estrogenic activity in a molecule with two benzene rings linked together via a short carbon chain (e.g., diphenylethane). (1) Soon thereafter, a synthetic, non-steroidal estrogen known as diethylstilboestrol (DES) was created from this basic molecular backbone. (1) By 1941, DES was an FDA approved drug, and by the 1950s, DES gained widespread popularity as the drug of choice for menopausal symptoms, cancer treatment, and prevention of miscarriages. (2)Diethylstilboestrol

DES sparked the interest of ambitious drug manufactures who saw this synthetic molecule as a potential “molecular backbone” which could be tailored for estrogenic activity, and patented for maximum profit.

Within months, a research group from the University of Edinburgh found that the addition of a benzene ring to the original diphenylethane structure created somewhat of an anti-estrogen known as triphenylethylene. (1) Although it had very weak estrogenic activity, it was called an anti-estrogen because it competed with the body’s more powerful estradiol for the ER receptors.

Although the complex estrogenic action of triphenylethylene was not fully understood, it was considered the perfect molecular platform for future drug development because of its high oral bioavailability and extended half-Triphenylethylenelife due to its lipophilicity (fat solubility). As it was later discovered, the estrogenic action could be manipulated with structural modifications for more specific agonist/antagonist actions. (3) Despite the lack of understanding of its many physiological effects, triphenylethylene would become the molecular backbone for generations of SERMs to come.

By the early 1940s, the world’s largest chemical manufacturers, including Imperial Chemical Industries (ICI), got word of the triphenylethylene development, and seized the opportunity to expand this new class of compounds. By the 1950s, the synthesis of new triphenylethylene based molecules had begun picking up momentum, as the first FDA approved SERMs started appearing on the market.

One of the first was Triparanol, which was sold as a cholesterol lowering SERM, until it was eventually pulled from the market in the 1950s for causing cataracts in patients. (7) Later, Ethamoxytriphetol (MER-25) was discovered and found to be a reliable contraceptive and anti-cancer agent in rats, but failed in humans due to the drug’s severe toxicity and stimulation of “acute psychotic episodes”. (6)

Despite these early warning signs, development continued.

Among one of the newer SERMs to appear in the late 1950s, was a mixture of two stereoisomers — zuclomiphene and enclomiphene — both having unique estrogenic and anti-estrogen actions. This mixture was collectively called clomiphene, and later marketed as Clomid.

ZuclomipheneEnclomiphene

Then, in 1962, ICI synthesized ICI-46474, another mixture of a trans and cis isomers with mixed estrogenic and anti-estrogenic activity. (7) Ultimately, the trans isomer was found to be the predominate anti-estrogen, which was isolated and eventually named tamoxifen, and later marketed as Nolvadex.

Originally, ICI pushed these new SERMs to market as a “morning after” contraceptives, which were eventually approved by the FDA. (4) Yet again, the profit hungry and presumptuous drug manufacturer based its findings on rat studies, which would prove to be a mistake upon subsequent human research that showed the SERMs induced, rather than inhibited ovulation. (4) Needless to say, tamoxifen was withdrawn as a contraceptive.

And remember DES, the original synthetic estrogen developed back in the 1930s? As it turned out, DES was found to increase the risk of breast cancer by 50%. Further research linked DES to millions of vaginal and testicular cancers among the children of mothers who took DES during pregnancy. (2, 5)

The light on synthetic anti-estrogens was dim, and by the late 1960s, there was little enthusiasm to continue R&D with triphenylethylene based SERMs, especially considering their inherently toxic effects (7, 10)

It wasn’t until 1971, that tamoxifen would be dug up from the dead and considered as a candidate for cancer treatment.

Treating cancer with a carcinogen –

When research is done on anti-cancer drugs (such as SERMs), the aim is to find a drug that prolongs life, with the least amount of acute side-effects. In other words, the goal isn’t so much about finding a cure, as it is finding something that can alleviate the symptoms and/or prolong life. Tamoxifen

For an estrogen dependant cancer, the idea was simple – Block the proliferative action of estrogen with an anti-estrogen and slow the cancer growth. What could be more appropriate than an already available, orally active, patentable synthetic estrogen such as tamoxifen? It was a practical shoo-in.

Therefore, in 1971, when drug researchers decided to examine all of the historical anti-cancer SERM data, they found that all of the SERMs showed anti-proliferative activity on estrogen dependant cancer, and all of them demonstrated some extent of toxicity. (10, 37-39) However, the SERM that happened to show the least amount of toxicity was tamoxifen. (clomiphene missed the mark by showing a high rate of cataract formation)

At the time, Pierre Blais, a well known drug researcher, commented on the finding (5) –

“Tamoxifen is a garbage drug that made it to the top of the scrap heap. It is a DES in the making.”

In spite of the criticism from a number of researchers, the FDA approved tamoxifen as a cancer treatment in 1977, and in 1985 ICI was awarded a US patent for tamoxifen in the treatment of breast cancer. (5) Soon, tamoxifen would become the most popularly prescribed cancer drug.

“Its FDA approved for cancer treatment. It must be safe!”

It’s wrong to assume that an “FDA approved” drug has a proven safety profile. The FDA has continually issued stronger health warnings for tamoxifen over the years. For instance, in 1994 the FDA demanded that the tamoxifen manufacturer Zeneca (an ICI sub-division), issue warning letters to health care practitioners about the increased risk of endometrial and gastro-intestinal cancers with tamoxifen use. Zeneca also reported adverse effects similar to those seen with DES, such as reproductive abnormalities in the animals whose mothers received tamoxifen. (remember, DES was the original synthetic estrogen, and also an analog to tamoxifen)

A number of cancer researchers have pointed out the health risks too, such as Elwood et al (6) –

“[Tamoxifen], therefore, is not appropriate for use in the general population because of the known increased risk of endometrial cancer”

“So why is tamoxifen the most popularly prescribed cancer drug, if it’s so toxic?”

The answer is simple. Tamoxifen is the lesser of two evils.

Tamoxifen remains the most popularly prescribed drug because it is one of the few drugs that has shown a “statistically significant” improvement of the survival rate of breast cancer patients.* (Not to mention, tremendous financial motives for its patent holder, Zeneca)

Remember, the goal in cancer treatment is to prolong life — even if it means committing to therapy that is potentially cancerous or injurious to future health (as confirmed in long-term follow ups and close examinations of tamoxifen patients).

So, perhaps the risks are worthy for the cancer patient, but are they worthy for the health conscious male?

* Most research has shown tamoxifen to improve the survival rate by 4-14%. For instance, over a 5 year period, 74% of the women survived who used tamoxifen, compared to 70% of the women on placebo. Depending on the type of cancer, this may translate into an extra 2-3 years of life for a cancer patient. (9) Continuing tamoxifen therapy for more than 5 years, results in increased tumor recurrences and serious side effects. (8)

Translating the science, for men’s health –

Fast forward 30 years, through hundreds of human and animal trials, and we find that the research is quite extensive, and contradicting. (21)

The damaging evidence from many early rat studies showed severely toxic effects, including the development of cancer in the liver, uterus, or testes upon tamoxifen administration. (30-34,41) However, this evidence was largely disregarded by further test tube studies on human cell-lines which appeared to show a lack of toxic effects. (21)

This misleading test tube data gave the green flag to perform large scale human studies with tamoxifen in the 80s and 90s. Even more misleading, the majority of the human research described tamoxifen as having a “low incidence of troublesome side effects” and that the “side effects where usually trivial”. (22)

As science would uncover, the lack of human toxicity reported in original tamoxifen research was a result of insufficient study duration, inability to detect low level DNA damage with insensitive methodologies, and/or misdiagnosis of collateral cancers as metastases from the breast cancer itself. (15, 21, 28-34)

A word on clomiphene (Clomid) –

Clomiphene (Clomid) consists of two stereoisomers which possess radically different pharmacodynamics. Zuclomiphene has predominantly estrogenic effects and slow clearance while the enclomiphene isomer has predominately anti-estrogenic effects and quick clearance. (9) This creates a divergent effects between estrogen blockage and estrogen stimulation and an acute imbalance once Clomid administration is discontinued. Bodybuilders will often complain of “estrogenic rebound” after stopping Clomid, which could be attributed to the lingering estrogenic isomer zuclomiphene as the anti-estrogenic enclomiphene has long cleared the system. (Recently, enclomiphene has been isolated by the pharmaceutical company Repros, for use in Androxal™.)

For all intents and purposes, tamoxifen is a superior SERM, simply for the fact that tamoxifen provides a purely anti-estrogenic isomer, whereas Clomid provides a mix of anti and pro estrogenic effects.

In regards to the health consequences about to be listed, it can be safely assumed that Clomid will share similar detrimental effects as tamoxifen, since it shares the same triphenylethylene backbone and carcinogenic tendencies. (44,45,57,58)

Liver cancer –

Originally, tamoxifen was accepted as being non-toxic to the human liver upon finding that tamoxifen did not cause noticeable liver damage (DNA adducts) during short-term test tube studies with human liver cells. (35,36)

However, it became apparent that test tube research was largely flawed due to the low rate of metabolism in such a superficial environment. (21) It was soon discovered that the hepatotoxic effects from tamoxifen stem from the metabolism and buildup of the a-hydroxytamoxifen and N-desmethyltamoxifen metabolites, which would only appear in an in vivo environment. (15) Surely enough, the results from the original rat studies showing dramatic carcinogenic effects on the liver, (30-34, 41) soon correlated with human data when researchers found the same type of liver DNA adducts in tamoxifen patients. (15, 28-34)

More recent human research has reported tamoxifen treated women to have 3x the risk of developing fatty liver disease, which occurs as soon as 3 months into therapy at only 20mg/day. (24-26) In some cases, the disease lasts up to 3 years, despite cessation of tamoxifen therapy. Five and ten year follow-ups with patients on long term tamoxifen therapy show cases of deadly hepatocellular carcinoma. (27-29)

In 2002, a bizarre study examined the use of tamoxifen for hepatocellular carcinoma treatment in humans. It was assumed that since tamoxifen could inhibit proliferation of breast cancer, it could offer the same benefit for liver cancer. The devastating results could not have been more indicative of tamoxifen’s hepatotoxic nature, as the tamoxifen treatment significantly increased the rate of death, compared to the group not receiving tamoxifen. (14)

Finally, in a case study reviewing tamoxifen induced liver disease; D.F Moffat et al made a profound statement –

“Hepatocellular carcinoma in tamoxifen treated patients may be under-reported since there may be reluctance to biopsy liver tumours which are assumed to be secondary carcinoma of the breast.”

In other words, it appears that liver carcinomas from a large number of breast cancer patients on tamoxifen therapy have been misdiagnosed as an infection from the breast cancer itself. (28)

Although tamoxifen induced liver cancer may take years to manifest in a healthy male, its damaging effects could easily be exaggerated by other popular hepatotoxic drugs, such as 17aa oral steroids. (15)

Prostate cancer –

In 1996, the International Agency for Research on Cancer (IARC) concluded that tamoxifen clearly promotes uterine cancer in humans – at a standard 20mg/day dose. (16,23,42) This is due to tamoxifen acting as an estrogen agonist in the uterus, presumably from the 4-hydroxytamoxifen metabolite, which triggers abnormal growth of the uterus and the formation of cancer causing DNA adducts. (33, 40)

Contrary to popular thought, these implications are quite scary for a male when we realize the male equivalent to the uterus is the prostate – which differentiates from the same embryonic cell line, shares the same oncogene, Bcl-2, and high concentration of estrogen receptors. In fact, there is no reason to assume that tamoxifen would not initiate the same cancerous growth in the prostate. (60-62) It is no wonder that tamoxifen failed as a treatment for prostate carcinoma. (43)

Note: This same risk would be applicable to Clomid, which has also been linked to uterine cancer and ovarian hyper-stimulation. (18, 19, 57, 59)

Libido reduction & erectile dysfunction –

Erectile dysfunction, low libido, and general impotence are typical complaints from men recently discontinuing steroids or HRT therapy, which is often combated by Clomid or Nolvadex, paradoxically so.

Regardless of any positive effects on fertility or testosterone levels, Clomid and Nolvadex use is highly correlated with erectile dysfunction, libido suppression, and even emotional disorders. (10,47)

Research with male breast cancer patients has also reported decreased libido, and thrombosis associated with tamoxifen use. (47) The thrombotic effect (blood vessel clogging) could explain the mechanism by which SERMs may inhibit erectile function, by reducing circulation to erectile tissue. (47, 52)

Increased susceptibility to gyno –

Tamoxifen is often used to combat gyno during cycle when “flare ups” occur. While tamoxifen may provide immediate inhibition of proliferation, and serve as valuable tool, it can actually increase future susceptibility to gyno.

This is caused by tamoxifen’s ability to up-regulate the progesterone receptor. (54-56) This can dramatically increase the chances of developing gyno in future cycles when utilizing progestin based anabolics such as Nandrolone (Deca) or Trenbolone (or any pro-hormone acting upon the progesterone receptor).

It is interesting to speculate. Is tamoxifen use directly related to the increased gyno occurrences seen with modern day steroid users?

Ocular toxicity –

Another possible side effect associated with SERMs is visual cloudiness, loss of vision and even cataract formation. Although this tends to be a more common side effect from high dosed SERM therapy, standard 20mg/day tamoxifen regimes have been reported to cause these symptoms of ocular toxicity. (17, 46)

Newer SERMs –

As the medical community became more aware of the side-effects associated with tamoxifen treatment, newer and safer SERMs, such as toremifene and raloxifene hit the developmental fast track. Toremifene appears to be less liver toxic, but it is a closely related analog of tamoxifen, so it also carries many of the related genotoxic effects. (48,49) Raloxifene

Raloxifene is a newer SERM based on a benzothiophene structure, which appears to make it less toxic in the liver, uterus or prostate. (50-52) Unfortunately, Raloxifene has been associated with a higher incidence of thromboembolism (52), and also has very low oral absorption, making it an expensive alternative at a typical dose (120mg/day). (53) Still, Raloxifene could presumably be equally effective as Clomid or Nolvadex at restoring HPTA function, while imparting fewer side effects. (53)

Newer SERMs are already being evaluated such as bazedoxifene, arzoxifene, and lasofoxifene, in hopes of reducing risk even further. (This further underscores the evidence of toxicity with the tamoxifen generation of SERMs)

What to do now?

Firstly, it should become a priority to create awareness about the possible side effects of SERMs. Once educated, users will be able to start reducing their use of these drugs, and begin adopting healthier, more responsible alternatives.

Carefully planned cycles, and the proper use of aromatase inhibitors (AIs) should prevail over haphazard combinations of excessive doses of aromatizing AASs — which require high doses of SERMs to reduce possible side-effects. Whereas avoiding SERMs in HRT will involve the natural clearance and management of endogenous estrogens.

It is important to maintain testicular function during a cycle for a quick and efficient recovery of natural testosterone production for PCT – negating the need for high dose 2-3 month SERM based PCT’s. (For more information on the proper use of hCG during cycle, visit here)

Thus, abolishing the bad habit of SERMing calls for community wide enlightenment with careful, comprehensive sharing and planning of worthy alternatives.

discuss this article in the forum

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