Plant flavanoid may help prevent leukemia

LONDON (Reuters) – Eating foods like celery and parsley which contain the naturally occurring flavanoid apigenin may help prevent leukemia, Dutch scientists said Thursday.

Maikel Peppelenbosch of the University of Groningen in the Netherlands said tests showed that apigenin — a common component of fruit and vegetables — was able to halt the development of two kinds of cells in leukemia and cut their survival chances.

The findings suggest apigenin could hold promise for preventing leukemia, Peppelenbosch said.

But he warned that his study had also found the compound has chemotherapy resistance properties, suggesting it might interfere with standard treatments for people already diagnosed with leukemia.

“Apigenin might be a useful preventative agent for leukemia, but it should not be taken at the same time as chemotherapy for established disease as it could interfere with the positive effects of treatment,” Peppelenbosch wrote in a study in the Cell Death and Disease scientific journal.

Flavanoids are compounds with antioxidant properties that protect cells against damage by oxygen molecules.

Previous studies have shown that apigenin, which is found in celery, parsley, red wine, tomato sauce and other plant-based foods, may also be beneficial in protecting against ovarian cancer.

http://www.reuters.com/article/idUSTRE60R2O920100128

History Corner: Friedrich Woehler 1800 – 1882

In 1828 the chemist Friedrich Woehler made a discovery that shocked him and overturned the reigning concept of how life relates to the rest of the world: he made the substance “urea” out of inorganic chemicals in a test tube.

Like most people of his time, Woehler believed that living things had a special mysterious “life force” that enabled them to make “living chemicals” like urea. This notion, which had developed from religious ideas, later came to be known and derided as “vitalism”. When Woehler made urea in a test tube, the life force theory was proven false and people began to realize that the structures and processes making up living things can be studied and manipulated in the same way that other material things can.

Links

History of Xenobiotic Metabolism (supplement)

The Organic Codes: The birth of semantic biology, p. 25

Cetyl myristoleate for worn-out knees

by Russell Mills

My knees began to hurt badly when I reached age 52, despite their not having been subjected to joint-pounding activities such as jogging or extensive hiking. The pain began around the time when I started using resistance machines at the gym to build up my legs. The mechanical stress of straightening the legs against a resistive force probably would not have caused knee problems for someone with larger and stronger bones and tendons than mine, but I have a light skeleton. So, in my case, it was not long before I could not manage a flight of stairs without clinging to the railing.

A friend suggested glucosamine-chondroitin. I was skeptical, but I tried it. To my surprise, it worked just fine. I continued using this combination of supplements, and for about 8 years my knees gave me no trouble. But then, it seemed, the treatment petered out. Actually, what happened was that I began using a more intensive workout regimen that put even more stress on the legs. The day after each workout the pain in my knees would flare up to worrisome levels, especially if I did much standing or walking. Doubling the dose of glucosamine-chondroitin didn’t help.

As luck would have it, around this time I was asked to write about cetyl myristoleate (CM) for the LifeLink website. CM, I learned, was being promoted by the supplement industry as an arthritis treatment, based mainly on some rat experiments done in the 1970s. Again, I was skeptical – but of course I tried the treatment anyway. And again, I was surprised and pleased at the results: my knee-pain went away except for minor soreness on days following an unusually intense session at the gym.

History of Cetyl Myristoleate

The story of CM’s discovery has a dramatic appeal that has caused it to be told in many places on the Internet. In brief:

Harry Diehl, a scientist at the National Institute of Arthritis, Metabolism, and Digestive Diseases during the 1950s and 1960s, became personally interested in arthritis when a neighbor developed a severe case of it. He established a laboratory in his home and began experimenting with mice.

When Diehl subjected mice to treatments that were known to induce arthritis in rats or in humans, the mice failed to develop arthritic symptoms. He suspected that the mice contained a factor that protected them from the disease. After years of work in his spare time, he was able to isolate a substance from mouse tissue which seemed to be responsible for their resistance to arthritis. That substance was cetyl myristoleate — a compound easily made by reacting myristoleic acid with cetyl alcohol. When Diehl tried giving cetyl myristoleate to rats, he found that it protected the rats from induced arthritis.

Diehl patented his discovery in 1977, receiving a “use patent” for rheumatoid arthritis. He tried to interest pharmaceutical companies in conducting human trials with cetyl myristoleate, but none were interested – perhaps they felt that a mere use patent does not give adequate protection from competitors. This promising treatment for arthritis was therefore put aside for about 15 years.

As Diehl got older, he himself began to develop osteoarthritis. After other treatments failed him, Diehl decided to make a batch of cetyl myristoleate and use it on himself. And it worked! Family members and friends wanted to try it, too. Soon they became customers, and cetyl myristoleate appeared on the market as a dietary supplement in 1991.

Clinical trials

There have been four clinical trials of CM, all performed during the past ten years and all reporting symptomatic improvement in arthritis patients given CM. Unfortunately only one of these studies was published in an accessible research journal, and all four studies lacked the statistical sophistication required to garner the approval of the arthritis research community.

The official (and correct) view of the situation is therefore that CM supplementation is not a proven treatment or preventative for arthritis. The reason is simply that”proof” requires sufficient evidence, and the studies that could supply this evidence have not been done. By the same token, it is equally true that CM has not been shown to be ineffective as an arthritis treatment or preventative. Nevertheless, the scanty evidence that does exist consistently points in the direction of effectiveness.

Individual reports

While reports from individual CM users are not considered scientifically convincing, there are plenty of such reports on the Internet from users who consider CM to be the “bee’s knees” of arthritis treatments. Nearly all of these testimonials, however, are found on websites of companies selling CM, and I’m reluctant to rely on these for information. Arthritis-oriented message boards have little to offer about CM, pro or con. Testimonials that seem to me more likely to be genuine are from people who have used CM to treat arthritis in their pets or horses. See http://www.my2by2.net/responseproducts/Testimonies.html, for example.

My own knee pain was not necessarily an arthritic condition – it may have stemmed from stress on ligaments or other tissue. I did not have it diagnosed by a medical practitioner. Whatever it was, it was triggered by resistance exercises or extended periods of walking or standing. And it was ameliorated by cetyl myristoleate in combination with glucosamine-chondroitin.

Dosage

Many CM vendors recommend a 30-day treatment consisting of a total of about 15 grams of cetyl myristoleate. This is supposed to suppress arthritis symptoms for a long period. They also claim that lipase enzyme must be taken to “digest” the cetyl myristoleate. Neither of these concepts makes sense.

While a limited course of treatment might possibly provide lasting protection in the case of an autoimmune disease like rheumatoid arthritis, it is unlikely to do so for osteoarthritis or other ailments resulting from chronic and ongoing injury, such as that caused by exercise. For these conditions it would make more sense to use CM on a continuing basis. My own experience suggests that 200 mg twice per day can be an effective regimen. It is important to read the product label carefully, since the CM ingredient is sometimes listed as a “complex”, and the amount of actual CM is given as a percentage of the complex.

I also disagree about the need for a lipase supplement. It is claimed that CM must be broken down to cetyl alcohol and myristoleic acid in order to be absorbed. This argument is nonsense. Even assuming that lipase can accomplish this conversion, there is no reason to think that the body would be able to put these components back together again after they get absorbed. Lipase was not used in the animal experiments that support the use of CM for arthritis. Nor did I use lipase with CM – yet my knees benefited anyway.

Some companies are selling CM in bottles with misleading potency information on the labels. For example, one product displays “500 mg” in large letters beneath the product name on the label, but closer inspection reveals that there is only 100 mg of cetyl myrisoleate in each capsule – the other 400 mg are related compounds that have less or no efficacy. Another product is promoted as “cerasomal” CM; the list of active ingredients contains 10 fatty acid substances, none of which seem to be cetyl myristoleate.

The genistein rush

PillManResearchers rush to discover the medicinal properties of soy-derived substances

A simple search of the medical research literature, using the search-word ‘genistein’, turns up more than 5500 research articles, most of them published in just the past several years. What is the reason for this surge of interest in a substance that, in the 1950s, was believed to be nothing more than a potential anti-fertility agent?

Genistein is an isoflavone extracted from soybeans. It is just one of several isoflavones found in soy and related plants. Daidzein and glycitein are two more, which share some of genistein’s physiological properties as well as having unique properties of their own. In the body, genistein inhibits various enzymes that have wide-ranging actions in many tissues. This means that its physiological effects are diverse and could impact many different ailments. The half-life of genistein supplements in the body is about 8 hours.

Genistein’s structural resemblance to sex hormones, such as estradiol, enables it to alter the body’s response to these hormones. Nonetheless, genistein proved to be a poor fertility blocker. It has, however, attracted the attention of researchers in a variety of fields, especially in cancer and cardiovascular medicine.

Clinical trials, animal studies, cell-culture experiments, and epidemiological studies have provided evidence for the following physiological effects of genistein:

  • reducing symptoms of allergic asthma
  • strengthening bone due to estrogen deficiency, especially in the spine
  • protection of nerve cells from damage caused by hormone shortages and Alzheimer’s proteins
  • breast enlargement
  • inhibition of growth and spread of various cancers – including cancer of the ovaries, colon, prostate, thyroid, skin, and head and neck; non-Hodgkin’s lymphoma, malignant melanoma, certain leukemias and lung cancers, and possibly breast cancer
  • counteracting the effects of the DeltaF508 mutation that causes cystic fibrosis
  • lowering body fat
  • improving insulin responses to blood sugar
  • lowering total cholesterol and LDL levels, increasing HDL levels
  • decreasing symptoms of Raynaud’s disease
  • inhibiting growth of atherosclerotic plaques in blood vessels
  • increasing arterial elasticity, lowering high blood pressure
  • preventing aging effects of UV light on skin
  • enhancing the bioavailability of many hard-to-absorb substances

Let us look at some of these effects in more detail.

Anti-cancer effects

Genistein has displayed antitumor, antimetastatic and antiangiogenic (suppression of blood-vessel growth) properties in tissue culture and in vivo. Several epidemiological studies suggest that soybean consumption may contribute to lower incidence of breast, colon, prostate, thyroid, and head and neck cancers – an effect that is attributed to genistein and other isoflavones. 1, 2, 3, 4, 5, 6

Other cancers that genistein has been reported to inhibit include: non-Hodgkin’s lymphoma, melanoma, lung cancers, and ovarian cancer. 2, 7, 8, 9

Tissue culture experiments suggest that genistein’s cancer-fighting effects occur at dosages that are hard to attain from food alone, unless one eats very large amounts of soy products. Reliable genistein dosing therefore requires the use of concentrated supplements. 4

One study reports that the supplement I3C (indole-3-carbinol) works synergistically with genistein to suppress estrogen-related cancers. 10

Anti-Alzheimer’s effects

Two studies in animals and tissue culture have shown that isoflavones, such as genistein, interfere with the formation of nerve-destroying protein deposits thought to be causes of Alzheimer’s and Parkinson’s diseases. This is not proof that isoflavones can treat these diseases, but it suggests that they might be worth trying. 11, 12

Bone-strengthening effects

The ability of genistein and related soy isoflavones to reduce post-menopausal bone-loss is attested to by many studies. These substances prevent bone loss and promote bone formation, especially in the spine. Among the dosage regimens found to be effective are: 1 mg/day genistein + 0.5 mg/day daidzein + 42 mg/day other isoflavones (biochanin A and formononetin, in this case); 54 mg/day genistein; 57 mg/day isoflavones; 65 mg/day isoflavones; 90 mg/day isoflavones. 13, 14, 15, 16, 17, 18

Short-term dietary soy stimulates breast proliferation in premenopausal, normal breast tissue. 19

Cystic fibrosis

One approach to treating cystic fibrosis is to inhibit a group of intracellular proteins called ‘chaperones’. (This approach applies mainly to a type of cystic fibrosis caused by the ‘DeltaF508’ mutation.) In tissue-culture experiments genistein was able to accomplish exactly that, and has therefore attracted the interest of patients with DeltaF508-related cystic fibrosis. 20

Body fat, insulin, and cholesterol

Genistein appears to increase the rate at which fats are ‘burned’ (metabolized) by the body, and to decrease the rate at which they are deposited in the tissues. 21

In clinical studies of humans and animals, the consumption of genistein and daidzein resulted in loss of body fat, lower fasting insulin concentrations, lower LDL (bad) and higher HDL (good) cholesterol, and improved insulin responses to blood sugar. Cholesterol benefits were seen at dosages of 42 mg/day of genistein plus 27 mg/day of daidzein. 22, 23

Cardiovascular effects

In addition to lowering LDL and raising HDL (mentioned above), genistein prevents the oxidation of LDL – a process thought to contribute to arterial plaques. 24

References

[1] Phase I pharmacokinetic and pharmacodynamic analysis of unconjugated soy isoflavones administered to individuals with cancer. [Abstract]

[2] Isoflavone genistein: photoprotection and clinical implications in dermatology. [Abstract] [Full text] [PDF (823 KB)]

[3] Soy isoflavones and cancer prevention. [Abstract]

[4] Phyto-oestrogens, their mechanism of action: current evidence for a role in breast and prostate cancer. [Abstract]

[5] Chemopreventive potential of epigallocatechin gallate and genistein: evidence from epidemiological and laboratory studies. [Abstract]

[6] Emerging evidence on the role of soy in reducing prostate cancer risk. [Abstract]

[7] Genistein sensitizes diffuse large cell lymphoma to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy. [Abstract]

[8] Oncogenic pathways implicated in ovarian epithelial cancer. [Abstract]

[9] Pilot study of a specific dietary supplement in tumor-bearing mice and in stage IIIB and IV non-small cell lung cancer patients. [Abstract]

[10] Indole-3-carbinol is a negative regulator of estrogen. [Abstract] [Full text] [PDF (194 KB)]

[11] Attenuation of neurodegeneration-relevant modifications of brain proteins by dietary soy. [Abstract]

[12] Genistein ameliorates beta-amyloid peptide (25-35)-induced hippocampal neuronal apoptosis. [Abstract]

[13] Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: a randomized double-blind placebo-controlled study. [Abstract] [Full text]

[14] Genistein appears to prevent early postmenopausal bone loss as effectively as hormone replacement therapy. [Abstract]

[15] The effects of phytoestrogen isoflavones on bone density in women: a double-blind, randomized, placebo-controlled trial. [Abstract]

[16] Dietary phytoestrogens and their effect on bone: evidence from in vitro and in vivo, human observational, and dietary intervention studies. [Abstract]

[17] The effect of isoflavones extracted from red clover (Rimostil) on lipid and bone metabolism. [Abstract]

[18] Soy isoflavones: hope or hype? [Abstract]

[19] Effects of soy-protein supplementation on epithelial proliferation in the histologically normal human breast. [Abstract]

[20] Pharmacological approaches to correcting the ion transport defect in cystic fibrosis. [Abstract]

[21] Usual dietary isoflavone intake and body composition in postmenopausal women. [Abstract]

[22] Beneficial role of dietary phytoestrogens in obesity and diabetes. [Abstract]

[23] The effect of isolated soy protein on plasma biomarkers in elderly men with elevated serum prostate specific antigen. [Abstract]

[24] Why are low-density lipoproteins atherogenic? [Abstract]

Analysis: Swine flu is not just a hoax by big pharma

As the dreaded autumn wave ends and official deaths remain relatively low, the backlash against the H1N1 pandemic response is in full swing. Claims range from a massive overreaction by health authorities to a conspiracy cooked up by big pharma. But while swine flu may have boosted profits for vaccine manufacturers, the reality of the pandemic is more complicated.

First off, the pandemic isn’t over. While cases in western Europe and North America have tailed off, the virus is still spreading in eastern Europe, Africa and Asia. Meanwhile, Europe and North America could see cases rise again, if the flu pandemic of 1957-8 is anything to go by (see graph).

By January 1958, following an initially low death rate, officials assumed the pandemic was over, and vaccine went unused. But then there was a wave of deaths in the US in February, which might otherwise have been avoided. “They had vaccine but they didn’t encourage its use,” says Anne Schuchat of the US Centers for Disease Control and Prevention in Atlanta, Georgia. To prevent a similar scenario, the CDC recommends continued vaccination. Yet several countries and US states have vaccine gluts, and many European countries are cutting orders and selling or giving vaccine away.

Even if we don’t see a 1958-style comeback, classifying the pandemic as a damp squib at this point would be premature. Although the World Health Organization’s official death toll stands at 13,000 worldwide, this is likely to be an underestimate. “We anticipate that these figures will be much larger,” Keiji Fukuda, head of flu at the WHO, told the press last week (PDF). Many cases are not seen by doctors, or are misdiagnosed: the CDC estimates that flu directly causes 2.7 times as many deaths as are officially counted in the US.

False perspectives

What’s more, straight death counts mask what was particularly scary about 2009 H1N1: that it doesn’t just strike the old and infirm. About 90 per cent of seasonal flu victims are over 65. In contrast, 88 per cent of H1N1’s victims have been under 65.

The perception that H1N1 is harmless may stem from ordinary people rarely seeing the severe cases, says D. A. Henderson of the University of Pittsburgh in Pennsylvania, who ran the CDC’s flu surveillance in 1957 and famously led the eradication of smallpox. Of a similar misperception in 1957, he says: “A quarter of Americans had flu, and there were excess deaths. But for one watching from close range, it did little more than disrupt school football schedules.”

What about the millions paid to vaccine companies? All the scientists contacted by New Scientist say launching vaccine production at the start of the pandemic was appropriate. “When a virus emerges from the animal reservoir you don’t know how it will behave,” says Ilaria Capua of the World Organisation for Animal Health’s flu reference lab in Legnaro, Italy. “We were quite lucky with this virus. Would you prefer to have no vaccine? This was the only thing we could do.”

NewScientist January 19, 2010 by by Debora MacKenzie: http://www.newscientist.com/article/dn18412