DHEA: For bones, mood, lupus, and lots more!

zarkovDHEA (dehydroepiandrosterone) is a substance produced in many tissues of the body, where it is used as raw material for making hormones, including testosterone and estrogens. Youthful bodies make large amounts of DHEA, but this production peaks at puberty in women and at about age 20 in men, then decreases dramatically with age. The intensifying DHEA deficiencies seen with aging, and the resulting decline in hormone levels, suggests that DHEA supplementation might correct age-related problems caused by shortages of these hormones.

DHEA has been studied by biological researchers since the 1950s, and has more recently been the focus of thousands of studies of its potential for treating a wide variety of ailments and for improving health. Many of these studies have led to positive results, others have not. The areas in which DHEA supplementation has shown especially good results include:

  • fat and obesity
  • hormone replacement
  • heart disease
  • cancer
  • muscle building
  • bone and osteoporosis
  • skin and aging
  • energy and fatigue
  • immunity and infections
  • cognition
  • mood and depression
  • lupus
  • menopausal symptoms
  • fibromyalgia
  • sexual function

There is also some evidence that DHEA may be useful in the following areas:

  • multiple sclerosis
  • Parkinson’s
  • allergies and asthma
  • schizophrenia
  • herpes encephalitis
  • diabetes
  • nerve cell growth and survival

Let’s look at several of these applications:

Fat and obesity. In 1988 a small clinical trial was conducted in which healthy men consumed 1600 mg/day of DHEA for 28 days. The astonishing result was an average loss of bodyfat of 31%, and a corresponding increase in muscle mass. Much smaller doses were used in later studies, and the fat losses were smaller but sometimes substantial. ‘DHEA has been shown to reduce the body’s production of cortisol’ the hormone that causes the storage of visceral (internal) fat and makes the belly protrude even when the skin is lean. DHEA also reduces the lipodystrophy caused by HIV drugs.

Bone and osteoporosis. In elderly women and men, bone density increases were seen with DHEA supplementation at 50 mg/day. A 2000 study, for example, showed significant increases in bone mineral density after six months of DHEA usage. Even a 25 mg/day DHEA regimen reduced joint pain in men.

Skin and aging. When DHEA was applied to the buttock skin of volunteers 12 times during 4 weeks it promoted the synthesis of procollagen and protein; the researchers concluded that DHEA could be an anti-aging agent for the skin. Improvement in skin pigmentation took place in elderly women given DHEA orally at 50 mg/day.  DHEA also accelerates healing of wounded skin.

Cancer. DHEA treatment inhibits cancers of the breast, prostate, colon, liver, and skin. Epidemiological studies have shown that women with high DHEA levels develop less breast cancer than those with low levels. DHEA has only mild side effects in other tissues, yet has a strong inhibitory effect in breast tumors. Current treatments for prostate cancer are based on the notion that androgens promote tumor growth, but recent evidence suggests the exact opposite: androgens (such as testosterone or DHEA) actually protect the prostate the prostate from tumor growth.

Uncovering lithium's mode of action

Though it has been prescribed for over 50 years to treat bipolar disorder, there are still many questions regarding exactly how lithium works. However, in a study appearing in this month’s Journal of Lipid Research, researchers have provided solid evidence that lithium reduces brain inflammation by adjusting the metabolism of the health-protective omega-3-fatty acid called DHA.

Inflammation in the brain, like other parts of the body, is an important process to help the brain combat infection or injury. However, excess or unwanted inflammation can damage sensitive brain cells, which can contribute to psychiatric conditions like bipolar disorder or degenerative diseases like Alzheimers.

It’s believed that lithium helps treat bipolar disorder by reducing brain inflammation during the manic phase, thus alleviating some of the symptoms. Exactly how lithium operates, though, has been debated.

Mireille Basselin and colleagues at the National Institute of Aging and University of Colorado, Denver, took a detailed approach to this question by using mass spectrometry analysis to analyze the chemical composition of brain samples of both control and lithium-treated rats stressed by brain inflammation.

They found that in agreement with some other studies, rats given a six-week lithium treatment had reduced levels of arachidonic acid and its products, which can contribute to inflammation.

In addition, they also demonstrated, for the first time, that lithium treatment increased levels of a metabolite called 17-OH-DHA in response to inflammation. 17-OH-DHA is formed from the omega-3 fatty acid DHA (docosahexaenoic acid) and is the precursor to a wide range of anti-inflammatory compounds known as docosanoids. Other anti-inflammatory drugs, like aspirin, are known to also enhance docosanoids in their mode of action.

Basselin and colleagues noted that the concentration of DHA did not increase, which suggests that lithium may increase 17-OH-DHA levels by affecting the enzyme that converts DHA to 17-OH-DHA.

By reducing both pro-inflammatory AA products, and increasing anti-inflammatory DHA products, lithium exerts a double-protective effect which may explain why it works well in bipolar treatment. Now that its mechanism is a little better understood, it may lead to additional uses for this chemical.

Science Centric | 22 May 2010 10:11 GMT

Source: American Society for Biochemistry and Molecular Biology (ASBMB)

Lithium Orotate targets Alzheimer's and other diseases of the brain.

And patients can’t afford to wait for clinical trials.

In 1997 a groundbreaking paper appeared in the Journal of Biological Chemistry, reporting that lithium interferes with a key process in the brain that damages nerve cells in Alzheimer’s disease. The researchers stated that “these findings could be exploited to develop a novel intervention for Alzheimer’s disease”.

More recent studies in cell culture and lab animals have added weight to this prediction and found additional ways in which lithium protects nerve cells and stimulates the repair of damaged nerve tissue. In a 2004 review of the subject, D.M. Chuang of the (U.S.) National Institutes of Health wrote: “The neuroprotective and neurotrophic actions of lithium have profound clinical implications. In addition to its present use in bipolar patients, lithium could be used to treat acute brain injuries such as stroke and chronic progressive neurodegenerative diseases.” Examples of such diseases are Alzheimer’s, Huntington’s, ALS, Parkinson’s, and other, less well-known, conditions.

Lithium salts have been used to treat manic-depression (‘bipolar disorder’) for more than 50 years, and are still considered to be among the best treatments for this ailment. ‘Bipolar’ patients usually use high doses of lithium carbonate (typically above 900 mg/day) and must receive professional guidance and testing for side effects.

At lower doses lithium has been used in recent years as a dietary supplement usually without medical supervision. Lithium Orotate is effective at less than 150 mg/day, with few or no side effects.

Although the lally-gaggers who control the world’s clinical research programs have yet to conduct a clinical trial of lithium as a prevention or treatment for Alzheimer’s or of any other neurodegenerative disorder, we needn’t wait for them to get their act together. Lithium is available as a nutritional supplement (in the U.S. at any rate). It has a very good safety profile at moderate doses – in fact, some evidence suggests that lithium may be an essential trace mineral in the human body.

Several other applications for lithium supplements have come to light recently:

  • protecting the brain from damage by alcohol
  • treating kleptomania
  • preventing symptoms of Fragile X Syndrome
  • a genetic flaw that is known to cause certain forms of autism
  • learning disabilities
  • anxiety disorders
  • mental retardation

LifeLink’s lithium product is the orotate salt of lithium, not the carbonate. This formulation was inspired by the work of Dr. Hans Nieper, the creative German physician, who used lithium orotate to treat:

  • depression
  • headaches
  • migraine
  • epilepsy
  • alcoholism

Nieper considered orotates to be superior to other anions as bioavailability enhancers for minerals like lithium. Furthermore, orotates have other useful properties:

  • protecting the heart from arrhythmias
  • reducing heart-attack damage
  • lowering mental stress
  • eliminating nerve-damaging deposits of lipofuscin and ceroid pigments.

'Fountain of youth' steroids could protect against heart disease.

A natural defense mechanism against heart disease could be switched on by steroids sold as health supplements, according to researchers at the University of Leeds.

The University of Leeds biologists have identified a previously-unknown ion channel in human blood vessels that can limit the production of inflammatory cytokines – proteins that drive the early stages of heart disease.

They found that this protective effect can be triggered by pregnenolone sulphate – a molecule that is part of a family of ”fountain-of-youth’ steroids. These steroids are so-called because of their apparent ability to improve energy, vision and memory.

Importantly, collaborative studies with surgeons at Leeds General infirmary have shown that this defence mechanism can be switched on in diseased blood vessels as well as in healthy vessels.

So-called ‘fountain of youth’ steroids are made naturally in the body, but levels decline rapidly with age. This has led to a market in synthetically made steroids that are promoted for their health benefits, such as pregnenolone and DHEA. Pregnenolone sulphate is in the same family of steroids but it is not sold as a health supplement.

“The effect that we have seen is really quite exciting and also unexpected,” said Professor David Beech, who led the study. “However, we are absolutely not endorsing any claims made by manufacturers of any health supplements. Evidence from human trials is needed first.”

A chemical profiling study indicated that the protective effect was not as strong when cholesterol was present too. This suggests that the expected benefits of ‘fountain of youth’ steroids will be much greater if they are used in combination with cholesterol-lowering drugs and/or other healthy lifestyle strategies such as diet and exercise.

“These ‘fountain of youth’ steroids are relatively cheap to make and some of them are already available as commercial products. So if we can show that this effect works in people as well as in lab-based studies, then it could be a cost-effective approach to addressing cardiovascular health problems that are becoming epidemic in our society and world-wide,” Professor Beech added.

The paper is published in Circulation Research.

###

For further information and interviews contact Paula Gould, University of Leeds Press Office – 0113 343 8059/4031 or p.a.gould@leeds.ac.uk

Notes to editors

1. “Pregnenolone sulphate- and cholesterol-regulated TRPM3 channels coupled to vascular smooth muscle secretion and contraction” by Jacqueline Naylor, Jing Li, Carol J. Milligan, et al is published in Circulation Research (doi:10.1161/circresaha.110.219329).

2. One of the UK’s largest medical and bioscience research bases, the University of Leeds is an acknowledged world leader in bioengineering, cancer, cardiovascular, epidemiology, molecular genetics, musculoskeletal, dentistry, psychology and applied health economics research. Treatments developed in Leeds are transforming the lives of people worldwide with conditions such as diabetes, HIV, tuberculosis and malaria.

The University is one of the UK’s leading research institutions with a vision of securing a place among the top 50 by 2015. www.leeds.ac.uk

3. The research was funded by the Wellcome Trust and the British Heart Foundation.

4. The Wellcome Trust is a global charity dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust’s breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests. www.wellcome.ac.uk

5. The British Heart Foundation (BHF) is the nation’s heart charity, dedicated to saving lives through pioneering research, patient care, campaigning for change and by providing vital information. But we urgently need help. We rely on donations of time and money to continue our life-saving work. Because together we can beat heart disease. For more information visit bhf.org.uk/pressoffice

Broccoli Component Limits Breast Cancer Stem Cells, Study Finds

A compound derived from broccoli could help prevent or treat breast cancer by targeting cancer stem cells — the small number of cells that fuel a tumor’s growth — according to a new study from researchers at the University of Michigan Comprehensive Cancer Center.

The study tested sulforaphane, a component of broccoli and broccoli sprouts, in both mice and cell cultures. Researchers found sulforaphane targeted and killed the cancer stem cells and prevented new tumors from growing.

“Sulforaphane has been studied previously for its effects on cancer, but this study shows that its benefit is in inhibiting the breast cancer stem cells. This new insight suggests the potential of sulforaphane or broccoli extract to prevent or treat cancer by targeting the critical cancer stem cells,” says study author Duxin Sun, Ph.D., associate professor of pharmaceutical sciences at the U-M College of Pharmacy and a researcher with the U-M Comprehensive Cancer Center.

Results of the study appear in the May 1 issue of Clinical Cancer Research.

Current chemotherapies do not work against cancer stem cells, which is why cancer recurs and spreads. Researchers believe that eliminating the cancer stem cells is key to controlling cancer.

In the current study, researchers took mice with breast cancer and injected varying concentrations of sulforaphane from the broccoli extract. Researchers then used several established methods to assess the number of cancer stem cells in the tumors. These measures showed a marked decrease in the cancer stem cell population after treatment with sulforaphane, with little effect on the normal cells. Further, cancer cells from mice treated with sulforaphane were unable to generate new tumors. The researchers then tested sulforaphane on human breast cancer cell cultures in the lab, finding similar decreases in the cancer stem cells.

“This research suggests a potential new treatment that could be combined with other compounds to target breast cancer stem cells. Developing treatments that effectively target the cancer stem cell population is essential for improving outcomes,” says study author Max S. Wicha, M.D., Distinguished Professor of Oncology and director of the U-M Comprehensive Cancer Center.

The concentrations of sulforaphane used in the study were higher than what can be achieved by eating broccoli or broccoli sprouts. Prior research suggests the concentrations needed to impact cancer can be absorbed by the body from the broccoli extract, but side effects are not known. While the extract is available in capsule form as a supplement, concentrations are unregulated and will vary.

This work has not been tested in patients, and patients are not encouraged to add sulforaphane supplements to their diet at this time.

Researchers are currently developing a method to extract and preserve sulforaphane and will be developing a clinical trial to test sulforaphane as a prevention and treatment for breast cancer. No clinical trial is currently available.

ScienceDaily (May 5, 2010)