Precursor Hormonal Longevity Factor Factor Four: DHEA-Forte
	Factor Four: DHEA-Forte is a pharmaceutical-grade, pure dehydroepiandrosterone, a precursor steroid hormone considered to be a key biomarker in determining biological age in both sexes.
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Research Report

Holistic Recommendations     Validation of Ingredients      References

REASONS TO CONSIDER (OVERVIEW)

• Men and Women over 40 years of age.

• Individuals with low DHEA blood serum levels.

• Women following menopause and/or hysterectomy.

• Men exhibiting a family history of cardiovascular disease.

• Individuals whose diet is high in refined carbohydrates.

• Individuals desiring to boost their immune system.

• Women on oral and vaginal contraceptives.
   

DOSAGE & DIRECTIONS

 

Men 40 to 55: Take one capsule daily with food on a consistent basis.
Men over 55: Take two capsules daily with food on a consistent basis.
Women over 40 or on contraceptives: Take one capsule daily with food on a consistent basis.
Individuals with low DHEA: Take two to three capsules daily until normal DHEA level has been achieved; then reduce dosage to one capsule or follow age guidelines above.
Women in post menopause or surgical menopause: Take two capsules daily with food on a consistent basis.

 

IMPORTANT NOTE:

DHEA (dehydroepiandrosterone) is considered to be a key biomarker in determining biological age in both sexes. DHEA, produced by the adrenal glands, is the only hormone that peaks early in life and starts to fall significantly thereafter, reaching a low by the age of sixty.

 

DHEA does not have a "feedback" mechanism so supplementation will not curb the body's production of this hormone.

 

CONTRAINDICATIONS & PRECAUTIONS

In women, high dosage levels of DHEA can result in hirsutism (excess body hair), fatigue, anger, depression, and acne rash. High dosage levels for prolonged periods may stimulate breast cysts or uterine fibroids.

In men, high dosage levels of DHEA may contribute to prostatic hypertrophy, low energy, and aggressive anger.

The dosage levels recommended in this report are well within safety tolerances and guidelines for normal DHEA usage. However, never take supplements at the same time as medications. If both must be taken with food, take them at different meals.

The following substances have been determined to lower DHEA levels: corticosteroids, progesterone and other oral contraceptives, cimetidine (Tagamet), lovastatin (Mevacor), ketoconazole (Nizoral), anticonvulsants, carbamazepine, phenobarbitals, and alcohol.

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Holistic Recommendations

 

It is important to note that significant amounts of DHEA are made only by humans and primates. Rodents, such as mice or rats, have little circulating DHEA in their blood so any dose given them would be a pharmacological dose.

Unfortunately, most studies involving DHEA have been conducted with rodents and many of the "miracle" claims being touted for DHEA have been based upon rodent studies. Much of the extrapolation from rodent studies to humans may be contradictory and, in fact, some of it has been proven to be false!

The information and recommendations provided within this report have been based upon the latest studies conducted on human subjects.

 

Recent research has found that DHEA supplementation in women increases natural levels of progesterone and ameliorates hot flashes. Only in women, in marked contrast with other mammals, can the ovaries be removed without a predictable reduction of sexual desire. From this, researchers have concluded that human female sexual desire has shifted somewhat from estrogens to androgens like DHEA, and from the ovaries to the adrenals.₂₉


Aging Biomarker

DHEA is a steroid hormone produced by the adrenal glands in both men and women.₇ This hormone is considered a key biomarker in determining biological age as it cycles on a life scale in both sexes. It is the only hormone that peaks early in life and starts to fall significantly thereafer.₈

DHEA is highest during the years of top physical condition, rising rapidly just before puberty, then spiking between ages twenty and twenty-five. It begins declining progressively from that point forward, reaching a low by the age of sixty and then slowly descends to less than five percent of peak adult levels after age 70.₉

The clear drop in men past forty is in sharp contrast to testosterone, which declines noticeably in men only after age sixty.₁₀

During the peak years between 25 and 30, men are believed to make 1 to 2 mg of DHEA and 10 to 15 mg of DHEAS per day, with women making somewhat lower amounts.₁₁

It is believed that approximately half of the androgen and estrogen precursors in the human body comes from the adrenal glands' production of DHEA.₁₂ As a result, the decline in DHEA production by the body reflects itself in the cells.

Based upon the foregoing, it has been suggested that supplementation with DHEA for those individuals 40 and older, bringing their levels back to those of youth, could extend longevity and improve the quality of life.

This suggestion gains further support in that DHEA, unlike other steroids, does not appear to be regulated by a "feed- back loop". DHEA supplements -except in very high dosages-
are not likely to stop the body's own production.₁₃

Autoimmunity

There are many autoimmune conditions of which systemic lupus erythematosus (SLE) is four times as common in women as in men. Symptoms include painful swollen joints, skin rash, and mouth ulcers.

SLE is more common than previously thought. A study in England found that 200 women out of 100,000 reported symptoms indicative of the illness.₁₄

A team of medical researchers from Japan determined that patients with SLE had low DHEA activity.₁₅

Physicians at Stanford University Medical Center conducted a study with ten female patients with mild to moderate SLE. The subjects were given 200 mg of DHEA daily for 6 months.

Following DHEA therapy, most of the symptoms were improved. The researchers concluded: DHEA shows promise as a new therapeutic agent for the treatment of mild to moderate SLE.₁₆

It is believed that DHEA therapy could benefit other auto-immunity diseases such as rheumatoid arthritis and multiple sclerosis. However, the studies on lupus have been the only well-controlled ones thus far. Further studies are clearly warranted.

Brain Enhancement

Researchers from the San Diego Medical School evaluated 13 men and 17 women who ranged in age from 40 to 70 years. In a placebo-controlled, cross-over trail, they provided 50 mg of DHEA nightly for 3 months.

Within two weeks, the DHEAS levels in the bloodstreams of those receiving supplements reached those found in young adults. The researchers concluded:

DHEA supplementation resulted in an increase in perceived physical and psychological well-being for both men and women. The subjects reported increased energy, a better mood, and an improved ability to deal with stressful situations.₁₇

DHEA has also been found to have a positive effect on memory. When 500 mg of DHEA was administered to subjects an hour before bed, there was a significant increase in recorded REM (dream) sleep for two hours afterward. Dreams are thought to facilitate memory consolidation.₁₈

Cancer

The majority of the research evaluating the role of DHEA in cancer has been done on rodents. Very little is known about its role in cancer prevention in humans.

As stated earlier in this report, the results of experiments involving rodents can be very different from results of similar studies with human subjects, especially since very little DHEA is found in the bloodstream of rodents.
DHEA levels can predict which women will get breast cancer up to nine years in advance,₁₉ and this steroid actually counteracts a well-known cancer-causing substance known as 12-0- tetradecanoyl-phorbol-13-acetate.₂₀

Whether long-term DHEA therapy will help prevent cancer in humans is undetermined at this time.

Diabetes

As humans age, the tissues develop a resistance to insulin and the glucose remains in the blood at a higher level. In a recent study 50 mg of DHEA was given daily for three weeks to 11 postmenopausal women.₂₁ The levels of triglycerides declined and DHEA enhanced tissue insulin sensitivity.

Another study also confirmed significant improvement in insulin sensitivity.₂₂ The researchers concluded: DHEA replacement may help attenuate age-related increases in insulin resistance.

It appears probable that DHEA has a positive effect in type II adult onset diabetes.

Heart Disease (CVD)

A study involving 49 males younger than age 56 who were survivors of a heart attack were compared to 49 other males of the same age group who had not experienced heart attacks. Those with prior heart attacks had significantly lower levels of DHEAS than the control group.₂₃

The researches concluded that serum DHEAS levels are inversely related to premature myocardial infarction in males and that this association is independent of the effects of several known risk factors for premature myocardial infarction.

Another study correlating DHEAS blood levels with the level of premature atherosclerosis in 206 patients under age 50 found that the levels of DHEAS were lower in the men who had coronary artery disease than the control group. This data lends further support to clinical studies suggesting that DHEA may play an important role in the pathogenesis of coronary disease.₂₄

A current study of 1,700 men aged 40 to 70 who had their DHEAS levels tested indicated those with the lowest levels were the most likely to have had heart disease, even after controlling for other risk factors such as smoking and diet.₂₅

Clinical studies thus far confirm that high DHEA(S) levels are protective of heart disease in men, but not as influential in women. It is probable, however, that supplementation with DHEA can slow the onset of coronary artery disease.

Immune System

A study was conducted of nine healthy men with an average age of 64 years. Each was given 50 mg of DHEA for 20 weeks at which time it was found that DHEA therapy had significantly elevated natural killer cells that fight infections.₂₆

Another clinical study vaccinated a group of elderly volunteers (over 65 years of age) with the influenza vaccine and compared them to another group similarly vaccinated but who had also received 50 mg of DHEAS for two consecutive days beginning on the day of the vaccination. The elderly who got the DHEAS had a significant improvement in their ability to develop anti-bodies to the influenza vaccine.₂₇

In short term studies on human subjects, DHEA has been found to be beneficial as a supplement in older individuals by improving the immune system.

Libido

DHEA may influence women more strongly than men where sexual desire is concerned. DHEA's favorable association with sex drive in women was demonstrated in a Crenshaw Clinic research protocol.₂₈ Increased levels of DHEA were associated with increased sexual desire.

Only in women, in marked contrast with other mammals, can the ovaries be removed without a predictable reduction of sexual desire. From this, researchers have concluded that human female sexual desire has shifted somewhat from estrogens to androgens like DHEA, and from the ovaries to the adrenals.₂₉

In men, the positive effects of DHEA are most apparent in those who have low androgen levels.₃₀,₃₁ for men, cardiovascular disease and stress are the greatest causes of sexual dysfunction.

DHEA blood levels drop drastically under stress, which is one of the primary reason that sex drive may decrease with acute or chronic stress, (and why men may lose erections when they worry about performance).₃₂

It is clear from numerous studies that DHEA does boost sex drive, especially in those who have low DHEAS levels.

Muscle Building

Aging is associated with a gradual shift from a young state characterized by anabolism, the building-up of muscles and tissues, to an aged state characterized by catabolism, the loss of muscle mass and strength.₃₃

DHEA in appropriate replacement doses appears to have remedial effects with respect to its ability to induce an anabolic growth factor, increase muscle strength and lean body mass in aging men and women, with no significant side effects.₃₄

Ninety-six patients with coronary artery disease had their DHEAS levels measured prior to starting a controlled exercise program. After 12 weeks, there was no change in the levels of DHEA leading researchers to conclude that exercise training alone has no significant impact on DHEAS.₃₅

In an earlier study conducted at the University of Rochester in New York, eight healthy young men were given 1,600 mg of DHEA for 4 weeks. The researchers found that DHEA had little influence on energy or protein metabolism.₃₆

DHEA in appropriate doses does appear to increase muscle strength and lean body mass in older men and women. However, it has little or no anabolic affect on younger men with normal DHEA blood serum levels and high dosage use by bodybuilders should be discouraged.

Osteoporosis

In surgical menopause with the removal of the uterus and ovaries, osteoporosis can occur within two years. After four years, over 60% of women demonstrate osteoporosis because of estrogen deprivation.₃₇

Research conducted in Japan on 120 postmenopausal women 51 to 99 years old found that women with higher DHEAS levels were more likely to have stronger bones.₃₈

Results of such studies demonstrate that DHEA is converted to estrone in osteoblasts, and this is important in maintaining bone mineral density after menopause.₃₉

DHEA therapy has the potential to influence stronger bone formation, especially in postmenopausal women.

Weight Loss

The reports in the medical literature evaluating the relationship of DHEA to weight loss have not been inconsistent.

Studies conducted in 1988₄₀ and 1991₄₁ under Dr. Nestler at the Medical College of Virginia in Richmond "suggest that DHEA may possess hypolipidemic and, possibly, anti-obesity properties".

Similar independent studies conducted by Dr. Usiskin₄₂ and Dr. Welle₄₃ in 1990 concluded that short-term administration of DHEA, in high doses, did not have much of an influence on weight.

Recent epidemiological studies conducted this year also do not support the theory, based upon rodent studies, that high DHEA(S) levels protect against obesity.₄₄

It appears unlikely that DHEA, regardless of dosage, will facilitate weight loss, however, DHEA may potentially be combined with other weight loss nutrients and herbs to have a synergistic effect. More research needs to be conducted.

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FACTOR FOUR FORMULATION

 

DHEA-Forte is manufactured from the steroidal saponin diogenin and converted by a series of eight chemical reactions into pure dehydroepiandrosterone.

When a DHEA capsule is swallowed, it is absorbed from the intestinal tract into the portal vein where it is transported into the liver. Most of the DHEA is metabolized by the liver before circulating throughout the bloodstream to the rest of the body.₁

When DHEA is metabolized, a chemical called sulfate is added which consists of the mineral sulfur combined with oxygen, creating DHEAS - short for DHEA-sulfate. About 90% of this steroid hormone is in the DHEAS form with the balance circulating as DHEA ₂

It is important to note that DHEA is lipophilic (soluble in fat) while DHEAS is water soluble. DHEA can cross the blood-brain barrier and influence the brain whereas DHEAS cannot.₃

Some manufacturers "micronize" DHEA, a process that creates smaller particles that can be absorbed from the intestines into the lymphatic system and partially bypass the liver, thus increasing the amount of "free" DHEA in the blood. Such micronization has been touted as enhancing the bioavailability of DHEA although there is very limited data supporting this claim.₄

Titan Laboratories does not micronize its DHEA because (1) limited data exists regarding the impact of DHEA on the brain.₅ Titan is therefore reluctant to alter or "shortcut" the natural pathway of DHEA as it is produced by the adrenals.

(2) DHEAS is consistently stable on a daily basis while free DHEA cycles throughout the day and may increase up to a hundredfold at a given moment or drop drastically under stress.₆ Again, Titan is reluctant to alter the naturally occurring 90/10 percentage relationship of DHEAS to free DHEA pending further clinical studies.

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References

1. Drucker, MD, et al., "Biologic activity of DHEA in man", J Clinical Endocrinol
Metab, vol 35, pp. 48-54, 1972
2. Ibid
3. Akwa, Y, et al., Journal Cell Biology, vol 121, no. 1, pp. 135-43, 1993
4. Casson, PR, et al., Seminars in Reproductive Endocrinology, vol 13, no. 4,
pp. 247-54, 1995
5. Robel, P, et al., Brain Endocrinology, Raven Press, NY, 1991
6. Glaser, J, et al., Journal of Behavioral Medicine, vol 15, pp. 327-41, 1992

 

Validation of Holistic Recommendations

7. Morales, AJ, et al., J. Clinical Endocrinol Metab., vol 78, pp. 1360-67, 1994
8. Orentreich, N, et al., J Clin Endocrinol Metab, vol 59, no. 3, pp. 551-54, 1984
9. Birkenhager-Gillesse, E, et al., An NY Acad Science, vol 719, pp. 543-52, 1994
10. dePeretti, E, et al., J Clin Endocrinol Metab, vol 47, no. 3, pp. 572-7, 1978
11. Longscope, C, "Metab of DHEA", An NY Acad Sci, vol 74, p. 143-48, 1995 12. Labrie, F, "Intracrinology", Mol Cell Endocrinol, vol 78, pp. C113-18, 1991
13. Ibid
14. Johnson, A, The Lancet, vol 347, pp. 367-9, 1996
15. Suzuki, T, et al., Clinical Exp Immunol, vol 99, no. 2, pp. 251-5, 1995
16. van Vollenhoven, RF, et al., Arthritis Rheum, vol 37, no. 9, pp. 1305-10, 1994
17. Morales, A, et al., "Effects of replacement dose of DHEA in men and women
of advancing age", J Clin Endocrinol Metab, vol 78, pp. 1360-67, 1994
18. Friess, E, Max Planck Inst of Psychiatry Clin Inst, Sci Report, pp. 108-9, 1994
19. Schwartz, AG, et al., Nutr Cancer, vol 3, pp. 46-53, 1981
20. Feher, TK, et al., Journal of Steroid Biochem, vol 23, pp. 153-7, 1985
21. Casson, P, et al., Fertil Steril, vol 63, no. 5, pp. 1027-31, 1995
22. Bates, CW, et al., Annals NY Academy Science, pp. 291-93, 1995
23. Mitchell, LE, Circulation, vol 89, pp. 91-93, 1994
24. Herrington, D, Annals NY Academy Science, vol 774, pp. 271-80, 1995
25. Feldman, H, Medical Tribune, p. 1, Apr. 4, 1996
26. Yen, SS, et al., Annals NY Academy Science, vol 774, pp. 128-42, 1995
27. Araneo, B, Annals NY Academy Science, vol 774, pp. 232-48, 1995
28. Crenshaw, TL, et al., J of Sex Martial Therapy, vol 13, pp. 239-52, 1987
29. Cumming, DC, et al., J Clin Endocrinol Metab, vol 54, pp. 1069-71, 1982
30. de Peretti, E, et al., J Clin Endocrinol Metab, vol 47, No. 3, pp. 572-7, 1978
31. Belanger, A, et al., J Clin Endocrinol Metab, vol 79, pp. 1086-90, 1994
32. Labbate, L, et al., Psychosomatics, vol 36, no. 6, pp. 555-60, 1995
33. Sahelian, R, DHEA, A Practical Guide, Avery Pub Gp, Gar City Pk, NY, 1996
34. Yen, SS, et al., Annals NY Academy Science, vol 774, pp. 128-42, 1995
35. Milani, R, et al., Am Journal Medical Science, vol 310, no.6, pp. 242-6, 1995
36. Welle, S, et al., J Clin Endocrinol Metab, vol 71, no. 5, pp. 1259-64, 1990
37. Rozenberg, SH, et al., "Age, steroids and bone mineral content", Maturitas, vol
12, pp. 137-43, 1990
38. Nawata, H, et al., J Steroid Biochem Mol Biol, vol 53, pp. 165-74, 1995
39. Gaby, A, Nutrition and Healing newsletter, Sept. 1995
40. Nestler, J, et al., J Clin Endocrinol Metab, vol 66, pp. 57-61, 1988
41. Nestler, J, jet al., J Steroid Biochem Mol Biol, vol 40, pp. 599-605, 1991
42. Usiskin, KS, et al., Int J Obesity, vol 14, no. 5, pp. 457-63, 1990
43. Welle, S, et al., J Clin Endocrinol Metab, vol 71, no. 5, pp. 1259-64, 1990
44. Barrett-Conner, E, et al., J Clin Endocrinol Metab, vol 81, no.1, pp.59-64,1996

 

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