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Cancer: Should Patients Take Dietary Supplements?
There continues to be controversy as to whether cancer patients should take certain vitamin and mineral supplements. Some in mainstream medicine have attacked the use of vitamin supplements as being potentially harmful, despite published scientific evidence indicating that cancer patients who supplement benefit. The criticism about cancer patients taking supplements is not limited to conventional oncologists. There have also been debates among Life Extension advisors as to what supplements are best for cancer patients to take. Unlike heart disease, cancer is a very complicated disorder. No one has definitively shown what supplements a cancer patient should take nor at what stage in the disease process the supplements should be initiated. It could be that some dietary supplements are of benefit at some phases of cancer treatment (such as enhancing immune function), but detrimental in others (such as protecting cancer cells against the effects of certain chemotherapy drugs). Most people familiar with published scientific literature are surprised that there is any argument over the value of dietary supplements and cancer treatment. The problem is the complexity of cancer compared to other diseases. For instance, there is a scientific consensus that folic acid is beneficial in cardiovascular disease patients because it lowers homocysteine and protects the arterial system via other mechanisms; no one argues against this. There is also substantial evidence that folic acid dramatically lowers the risk of many forms of cancer; few scientists disagree with this premise either. However, the role of high-dose folic acid in the treatment of cancer is not as clear-cut. Every human and animal cancer study indicates that folic acid improves survival, yet those familiar with the molecular actions of folic acid are concerned that very high amounts could potentially facilitate cancer cell propagation. In the following section, we review all studies involving the use of dietary supplements by human cancer patients. We also discuss reasons why some scientists believe that cancer patients should approach supplementation with a degree of caution. The reader should know that no organization has ever methodically analyzed the scientific literature to address the complex issue of using dietary supplements in the treatment of cancer. Although articles have been written about isolated effects of certain nutrients, there has not been an attempt to consolidate this knowledge in a way that provides practical guidance for the cancer patient.
Human Research on Cancer and Dietary Supplements
Although there are hundreds of published studies showing that the ingestion of certain nutrients may reduce cancer risk, relatively few investigate the effects of dietary supplement intake by those already stricken with cancer. This paucity of data has enabled mainstream oncologists to speculate that certain dietary supplements might protect cancer cells from apoptosis (programmed cell death). The assertion made by some oncologists is that there may be a risk when cancer patients take certain dietary supplements. To get the bottom-line facts on what happens to cancer patients who take dietary supplements, a MEDLINE search was conducted using key words to access all peer-reviewed published studies relating to groups of cancer patients who used various dietary supplements. The criteria for the studies selected was that the dietary supplement had to show an effect on the clinical outcome of the patient--preferably relating to long-term survival--as opposed to therapies that offer a short-term benefit, such as mitigating chemotherapy toxicity. Oncologists generally acknowledge that supplements can mitigate chemotherapy and radiation therapy side effects. The question is whether cancer patients taking supplements are actually surviving longer. Below is a synopsis of the MEDLINE findings:
1. A study was conducted on non-small cell lung cancer patients over age 60 that had already had the primary tumor(s) surgically removed. The prognosis for this type of cancer is grim. The doctors compared vitamin users to nonusers and measured blood folate as an indicator of folic acid intake. The median survival for the nonusers was only 11 months compared to an astounding 41 months for the vitamin users. Supplement users, in other words, survived almost four times longer than nonusers. In those patients with higher blood levels of folate, there was a 68% improvement in survival. Because the doctors adjusted for other mortality factors, the findings of this study suggest that cancer patients should take vitamin supplements (Jatoi et al. 1998).
2. A more specific study looked at a group of transitional cell bladder cancer patients. One group was given BCG (tuberculosis vaccine) immune-augmentation therapy plus the recommended daily allowance (RDA) of vitamins. The second BCG-treated group received the RDA plus 40,000 IU of vitamin A, 2000 mg of vitamin C, 400 IU of vitamin E, 100 mg of vitamin B6, and 90 mg of zinc. After 5 years, the tumor recurrence rates were 91% in the group receiving the low-potency RDA vitamins, but only 41% in the mega dose vitamin group. In this study, large doses of vitamins resulted in a 55% reduction in tumor recurrence (Lamm et al. 1994).
3. Malignant melanoma is virtually impossible to stop once it has spread beyond the primary lesion. A rare form of melanoma occurs in the iris of the eye, and it is considered high risk because it is often found too late. Nine random high-risk patients with T3 melanoma of the eye first underwent standard conventional therapy to eradicate the primary tumor. These patients were then put on a supplement regimen consisting of folic acid, trace minerals, amino acids, and fatty acids. After 80 months of follow-up, none of these nine patients experienced recurrent disease, which was significantly better than a similar group of high-risk melanoma patients who did not receive these supplements. (The control patients consisted of similar adjusted T3 cases selected from the Swedish official registries and T2 patients from Germany.) Because 100% of these high-risk patients were free of disease after almost 7 years, this provides further piece of evidence of the potential value of dietary supplementation in the cancer patient (Tallberg et al. 2000).
4. Breast cancer patients commonly undergo chemotherapy to reduce the risk of future metastasis. Despite the severe toxicity of chemotherapy, many women experience aggressive metastatic disease and die. Once metastatic disease manifests, the 5-year survival rate is only 15%. A review was conducted of various chemotherapy regimens in order to ascertain the percentages of objective remissions in metastatic breast cancer patients. Of the drugs tested, 5-fl o u o rouracil (5-FU) came in last, but when folic acid was added, objective remissions increased significantly (Kreienberg 1998).
5. The drug 5-fluorouracil (5-FU) is commonly used in visceral cancers (such as colon, liver, pancreatic), but has not shown a high degree of efficacy. A randomized trial of patients with metastatic colorectal carcinoma compared the effects of 5-FU administered alone and in combination with folic acid. Both groups were comparable in respect to age, sex, and numbers of metastases. Compared to the group receiving 5-FU by itself, the patient group receiving the 5-FU plus folic acid experienced a 40% arrest of tumor growth and a 76% overall reduction in tumor progression indicating a 47% difference between the 5-FU and folate group and the 5-FU group. Survival time in the group receiving the 5-FU plus folic acid was 47% greater than the group receiving the 5-FU by itself. The addition of folic acid to this chemotherapy drug regimen resulted in an improvement in the therapeutic profile and a significant prolongation of the survival time (Loffler et al. 1992).
7. Advanced cancer patients exhibit multifaceted defects in their immune capacity that are likely to contribute to an increased susceptibility to infections and disease progression. This immune impairment also constitutes a barrier to effective immunotherapeutic interventions. A chronic inflammatory condition associated with increased oxidative stress has been suggested as one of the responsible mechanisms behind the tumor-induced immune suppression. A study was conducted on 12 advanced colorectal cancer patients to ascertain if supplementation with the antioxidant vitamin E could enhance immune functions. These colorectal cancer (Dukes's C and D) patients received a daily dose of 750 mg of vitamin E beginning 2 weeks prior to intervention with chemotherapy or radiation treatment. The results showed that short-term supplementation with vitamin E led to increased CD4:CD8 ratios and enhanced capacity of their T-cells to produce the T helper 1 cytokines, interleukin 2, and IFN-gamma (Malmberg et al. 2002). There are other human studies showing a benefit when cancer patients take dietary supplements. We could find no studies on MEDLINE indicating a detrimental effect. The findings from animal studies (reported on next) support the positive human findings that show that dietary supplements appear to enhance survival.
Animal Research on Cancer and Dietary Supplements
To obtain additional information about what happens when an organism afflicted with cancer is administered dietary supplements, we extended our MEDLINE search to in vivo animal studies. As was done with the human study search, keywords were aimed at accessing all peer-reviewed published studies relating to the effects of dietary supplements on animals with different forms of cancer. The criteria for studies selected were that the dietary supplements had to show an effect on survival. Below is a synopsis of the MEDLINE findings:
1. A debate among medical oncologists relates to the combined use of certain dietary supplements and chemotherapy. A study on rat mammary tumors provided some interesting data but also revealed part of the controversy. In this study, rats were administered one of three chemotherapy drugs (5-FU, doxorubicin, or cyclophosphamide) and then provided with a wide dosage range of folic acid. In the folic acid-deficient group, tumor growth was impeded. However, when higher amounts of folic acid were administered, even greater tumor growth-inhibiting effects were observed. When looking at the data, low folate inhibited tumor growth by an average of 41%, moderate folic acid supplementation inhibited tumor growth by an average of 67%, and very high folic acid administration resulted in an average of 75% in tumor inhibition. Folic acid supplementation doubled the efficacy of one of the drugs (cyclophosphamide) and improved survival in the 5-FU treated animals (Branda et al. 1998).
2. In a group of mice with ascites sarcoma, a four- to six-fold surplus of folic acid in oral application reduced the toxicity of the chemotherapy drug methotrexate. Moreover, adding these high amounts of folic acid into their drinking water prolonged the survival of these mice (Motycka et al. 1975).
3. In a group of mice bearing leukemias and solid tumors, a combination of oxidized vitamin C and vitamin B12 inhibited division of the cancer cells. The mice were injected with the vitamins and after 19 days, all of the controls had died, whereas more than 50% of the mice were alive after 60 days in the vitamin-treated group. This study demonstrated that when B12 is combined with vitamin C, the cobalt nucleus of B12 attaches to vitamin C, forming cobalt ascorbate. Additional tests proved that cobalt ascorbate plus vitamin C inhibited tumor cells (Poydock 1991).
4. The effects of methylcobalamin (vitamin B12) were examined in mice with liver, lung, and Ehrlich ascites tumor cells. The growths of tumors in some groups of the mice were suppressed by the 7-day administration and their survival was longer than that of untreated mice (Shimizu et al. 1987). In a contradictory animal study, the effect of methylcobalamin and vitamin B12 reduced the survival of rats with liver cancer. This is the only study where vitamins actually inhibited survival (Kal'nev et al. 1977).
5. Cancer spreading (metastasizing) throughout the body often culminates in death. Immune suppression is one mechanism that cancer cells use to establish colonies (metastatic lesions). Scientists investigated the effects of an antioxidant called astaxanthin in stress-induced, immune suppressed in mice. When exposed to stress, the number of natural killer cells (NK) and other immune cells was reduced and an increase in liver lipid peroxidation was observed. After 4 days of astaxanthin administration, immune dysfunction induced by stress improved. In this same study, cancer cells were injected into mice and the effects of tumor development and metastatic lesions were evaluated in response to induced stress. Daily administration of astaxanthin for 14 days markedly attenuated the promotion of hepatic metastasis induced by stress. The results of this study suggest that the antioxidant, astaxanthin, improves antitumor immune response by inhibiting lipid peroxidation induced by stress (Kurihara et al. 2002).
Despite these studies indicating that supplements confer a significant anticancer benefit, there are certain supplements that cancer patients might consider avoiding, at least during active treatment. These issues are addressed in the next section and in the protocols entitled Cancer Chemotherapy and Cancer Radiation Therapy that appear in this book.
Do Antioxidants (Concurrent with Conventional
Bolster or Diminish Survival Odds?
Abram Hoffer, M.D., Ph.D., contends that the concept of antioxidants decreasing the efficacy of chemotherapy is conveyed more and more by orthodox oncologists. It is, in fact, speculated that the number of oncologists opposed to patients taking antioxidants while receiving chemotherapy may be as high as 75%.
Although antioxidant therapy is a hotly debated issue, the benefits derived from chemotherapy are equally so. Even within the field of standard oncology, there is debate as to the merit of chemotherapy except for in a small number of cancers (Moss 1995). Before one can claim that antioxidants should be withheld, credible evidence should be presented showing that chemotherapy has merit. At the Comprehensive Cancer Care 2001 Conference, it was reported that 31% of cancer patients abandon chemotherapy before completion due to intolerable psychological and physical stresses.
Amifostine, a synthetic variant of the amino acid cysteine, is prescribed to reduce radiation toxicity. Amifostine reduces toxicity of treatment without depreciating the anti-cancer effects (Mehta 1998). There is no evidence of defusing the effects of radiotherapy with Amifostine (Perez et al. 1998). Cardiozane (ICRF187), an antioxidant with 500 papers showing its relative safety, is prescribed to counter Adriamycin toxicity (Alderton et al. 1992). Mesna, another synthetic antioxidant, makes possible the use of the anticancer drug Ifosfamide, which (otherwise) damages the urinary system (Brock et al. 1979). Synthetic antioxidants, though somewhat toxic in nature, do not generate controversy because they are physician-prescribed and not patient-managed. It appears only orthomolecular or natural antioxidants are potentially dangerous, according to mainstream oncologists.
Most natural antioxidants, including vitamin C, are under ongoing scrutiny and often attack. The charges that vitamin C impairs the effects of chemotherapy appear to have kindled from an interview conducted with Larry Norton, a chemotherapist with a focus on breast disease at Memorial Sloan Kettering. An account of the interview that ran on the front page of newspapers (in 1997) charged that Sloan Kettering researchers had found that vitamin C blunted the effects of chemotherapy in breast cancer cells.
Dr. Charles Simone, a respected voice in natural medicine, clarified the media hype by saying that researchers had simply determined that tumor cells (injected with vitamin C) take up larger amounts of the nutrient than noncancerous cells (Agus et al. 1999). The story that was ultimately reported had a different slant, that is, because tumor cells are vitamin C responsive, ascorbic acid stymies the effects of chemotherapy by neutralizing free radicals , molecules produced by various chemotherapeutic drugs to kill the cancer. Dr. Simone cautions that jumping from a fact (cancerous cells take up more vitamin C) to a factoid (vitamin C interferes with chemotherapy/radiation therapy) is an unfortunate leap that may have impeded progress for many cancer patients.
Dr. Simone cited more than 350 studies, involving 2000 cancer patients that showed that antioxidants extended the life span of cancer patients and improved quality of life. One such study involved 50 early stage breast cancer patients, some of whom were relegated to radiation therapy and others to a combination of radiation and chemotherapy. All participants (in union with conventional therapies) took large doses of nutrients. More than 90% of both groups noted improvement in their physical symptoms, cognitive ability, sexual function, general well-being, and life satisfaction. Not one subject in either group reported a worsening of symptoms (Simone et al. 2000).
LE Magazine June 2006
Dietary Supplements Attacked by the MediaBy William Faloon
The media has launched an assault against healthy lifestyles and some popular dietary supplements. The public has been thrust into a state of confusion by these frenzied media reports that contradict long-established scientific principles.
I am impressed by how quickly Life Extension members picked up on the errors contained in the studies used to ridicule those who practice healthy living.
The outrage over these biased reports was not limited to Life Extension members. The front page of the Wall Street Journal carried a scathing report about how the Federal Government issued misleading press releases that gave the media the green light to discredit alternative approaches to disease treatment. According to the Wall Street Journal:
"Design problems in all the trials means the results don't really answer the questions they were supposed to address. And a flawed communications effort led to widespread misinterpretation of the results by the news media and the public." 1
What you are about to read might at first seem unbelievable. Please remember, however, that the studies we describe were conducted by mainstream doctors who know virtually nothing about natural ways to prevent and treat disease.
As you will also find out, many of the doctors who designed and authored these flawed studies received financial compensation from the very pharmaceutical companies that stood to gain the most by deriding low-cost natural approaches to disease prevention.
Media says: Eat all the fat you want.Does eating a low-fat diet reduce the risk of contracting common diseases? The media answered this question by boldly proclaiming that there is no benefit to women eating a low fat diet. According a lead article in the Washington Post:
"Low-fat diets do not protect women against heart attacks, strokes, breast cancer or colon cancer." 2
The study that this headline story was based on, however, failed to differentiate between health-promoting fats (such as monounsaturated and omega-3 fats) and lethal trans fats. 3-5 It was long ago established that over-consumption of trans fats is related to atherosclerosis, cancer, and chronic inflammation. 6-12 Furthermore, there was no attempt to measure the balance of omega-3 and omega-6 fatty acids. Most Western diets contain an abundance of omega-6 fatty acids (e.g., corn, safflower oils) and completely inadequate levels of omega-3 fatty acids (such as fish oil, flaxseed, and walnut oils).
The "excuse" some researchers gave when confronted with these flaws was that when the low-fat studies were designed, doctors did not know the difference between friendly and deadly fats. The facts are that when these studies were designed, there was an abundance of published scientific data to show that friendly fats like olive oil 13-35, flax oil 36-43, and fish oil 44-57 conferred life-saving benefits while trans fats were proven killers.
Researchers also were unable to rigorously monitor whether or not the participants actually followed low-fat diets. Food-intake questionnaires were used, which are notoriously unreliable indicators of food intake.
In what is perhaps the most outrageous defect in these studies, only 1 in 7 women actually achieved the low-fat diet threshold! Specifically, only 14.4% of the "low-fat" group really followed a low-fat diet. Furthermore, the average reduction in total fat intake in the "low-fat group" was only 8.2% (with just a 2.9% decrease in saturated fat intake). Assuming that this paltry 8.2% figure is accurate (i.e., that the food questionnaires were completely accurate), this number does not come close to the percentage of fat-calorie reduction other studies have shown is needed to reduce disease risk.
These flaws rendered this multimillion-dollar low-fat diet study worthless. This did not stop major newspapers, however, from featuring articles on their front pages stating that reduced-fat diets provide no health benefits.
Media says: calcium does not protect bonesOne of the most controversial media stories dealt with a study that supposedly showed that women who took calcium and vitamin D supplements did not obtain any protection against hip fracture. 58
We at Life Extension initially thought this negative finding was because the active group was not given magnesium, zinc, manganese, and other nutrients that are essential to maintaining optimal bone density.
When we got our hands on the study itself, we were startled to find that the women in the study who actually took their calcium and vitamin D supplements suffered 29% fewer hip fractures. 58 This was contrary to what the headlines said. It turned out that the media believed the government's negative press release and obviously did not read the actual scientific study.
Many study subjects failed to take their calcium-vitamin D supplementsIn this study to evaluate the efficacy of calcium and vitamin D compared to placebo, it was startling to learn that many women in the active arm did not take their calcium-vitamin D supplements! According to the study report, about 40% of the women assigned to take calcium and vitamin D did not achieve a standard rate of compliance with their supplements!
When the entire study was tallied, the women in each group (active and placebo) officially remained in their respective group, whether or not they actually followed the study protocol. This meant that women in the active group (the one given the calcium-vitamin D supplements) were counted as having taken the calcium-vitamin D, whether they really took the supplement or not. According to the scientists who conducted this study:
"Participants were followed for major outcomes, regardless of their adherence to the study medication." 58
The "study medication" mentioned above is the calcium-vitamin D supplement. The fact that a study could be published in a medical journal "regardless" of whether the participants actually took the active ingredient defies logic. The application of common sense would invalidate the findings of this study, regardless of what statisticians might argue.
Placebo group allowed to take calcium and vitamin DFurther confounding the study results were previously unheard-of rules that allowed the placebo group to take multi-vitamin, calcium, and vitamin D supplements on their own if they wanted. It turned out that many in the placebo group were taking calcium and vitamin D. According to the study design, since they were part of the placebo arm, they were officially not taking calcium-vitamin D supplements, even though many of them were indeed taking calcium-vitamin D.
The fact that the placebo group was freely allowed to take multivitamins, calcium and vitamin D meant that many of the placebo participants may have consumed more bone-protecting nutrients (including boron, magnesium, zinc, and manganese) than the active group (who were supposed to be taking only calcium and vitamin D). By failing to separate who was really taking bone-protecting supplements, it was impossible draw a scientific conclusion, yet the media boldly asserted that there was no difference in the hip fracture rate in the group assigned the calcium-vitamin D supplements (many of whom were not taking their supplements) as compared to the placebo group (many who were consuming calcium, vitamin D, and other bone-protecting supplements).
Bone building hormones and drugs also permittedNot only was the placebo group allowed to take their own calcium, vitamin D, and other bone-maintenance supplements, but both groups were also allowed to take drugs (bisphosphonates and calcitonin) and hormone therapies that are known to prevent bone loss and restore bone density. In this study that the Federal government spent over $10 million funding, virtually anything was allowed.
Media grossly misleads publicWhile the study itself was badly flawed, the media distortion of the findings is nothing short of abominable. Front-page news stories declared calcium-vitamin D supplements had been proven worthless, yet the actual study stated:
"Women receiving calcium with vitamin D supplements had greater preservation of total-hip bone mineral density. 58
"Among women who were adherent (i.e., those who took at least 80 percent of the study medication), calcium with vitamin D supplementation resulted in a 29 percent reduction in hip fracture. 58
"The effect of calcium with vitamin D might require higher doses of vitamin D than were used. 58
"It is also plausible that there was a benefit only among the women who adhered to the study treatment." 58
As you will read in the June 2006 issue of Life Extension magazine, there are even more serious flaws in this calcium-vitamin D study than what I just described, but it is safe to state that this may have been one of the most poorly designed studies in the history of modern medicine. This did not stop the media from turning it into one of the main headline news stories of the day.
Millions of American women will discard their calcium and vitamin D supplements based on these false and misleading headlines. This is great news for pharmaceutical companies that sell expensive drugs to treat osteoporosis.
Biased attack on glucosamineThe next victim of the media's witch hunt was glucosamine, which was one of several agents tested as a treatment for osteoarthritis of the knee.
The media's deceptive stories were based on a study of people with mild to severe knee pain who were given a form of glucosamine not normally found in dietary supplements. Some participants received this form of glucosamine by itself, while others were given chondroitin sulfate by itself, a combination of glucosamine and chondroitin, or the drug Celebrex®.
The results of this study were encouraging, but the media distorted the findings in a way that made it appear that glucosamine-chondroitin supplements were of little value. A number of media outlets proclaimed that arthritis sufferers were wasting their money by taking glucosamine. While this made compelling headlines, it did not accurately convey what was written in the actual study.
The findings from the actual scientific study made it clear that glucosamine and chondroitin taken together were effective in those with moderate to severe arthritis of the knees.
Media may not have read glucosamine studyThe media appears to have relied on a biased editorial that accompanied the actual scientific report on glucosamine. For instance, the New York Times said the following about this arthritis study:
"No effect was found for glucosamine, chondroitin, or the combination of both." 60
Yet on page 804 of the study (which was published in New England Journal of Medicine, the following was stated about patients with moderate to severe arthritis of the knee who took glucosamine-chondroitin therapy:
".combined treatment was significantly more effective than placebo" 59
The actual study went on to say that in those with moderate to severe arthritis, the combination of glucosamine-chondroitin resulted in a 24.9% to 26.4% improvement in pain relief. This result exceeded the 20% response to treatment measurement that the scientists themselves stated would prove efficacy. 59
As far as reversing the structural damage inflicted to the knee by osteoarthritis, the scientists stated:
"Treatment with chondroitin sulfate was associated with a significant decrease in the incidence of joint swelling, effusion, or both." 59
In their concluding remarks, the scientists stated:
"Our finding that the combination of glucosamine and chondroitin sulfate may have some efficacy in patients with moderate-to-severe pain is interesting, but must be confirmed by another trial." 59
As anyone who understands the English language can read, even this different form of glucosamine, when combined with chondroitin sulfate, demonstrated efficacy in patients most in need, i.e., those with moderate-to-severe pain! The media overlooked these clearly written findings in their haste to viciously attack glucosamine and chondroitin dietary supplements.
Better than Celebrex®One of the arms in this arthritis study was given 200 mg a day of Celebrex®, an FDA-approved arthritis drug.
In patients with moderate to severe knee pain, however, the only treatment that showed significant benefit was glucosamine-chondroitin.
The media, however, chose to tout the mediocre benefits that Celebrex® showed in this study. For instance, in a widely distributed Associated Press story, the following was stated about Celebrex®:
"The drug Celebrex did reduce pain -- 70 percent reported improvement -- affirming the study's validity." 61
The inclusion of Celebrex, in fact, did not affirm the study's validity considering that 60 percent of the placebo group also reported improvement. The authors of this study stated that compared to placebo, Celebrex® was " not significantly better." 59
In the concluding remarks, these scientists stated:
"However, even the effects of celecoxib (Celebrex®) were smaller than those seen in other studies." 59
The media exaggerated the benefits of Celebrex while vilifying glucosamine-chondroitin, carrying on a long tradition of bias against dietary supplements.
The arthritis study's disappointing findingsThe data that caused these negative media stories involved study subjects with mild knee pain. The scientists noted that in these patients, "differences between placebo and the various agents were relatively small." 59
As compared to placebo, here were the pain score percentage point improvements for overall groups within this study: 59
|Therapy||Improvement in Primary Pain Score||Improvement in Secondary Pain Score|
|Glucosamine HCL only (note this is not glucosamine sulfate)||3.9%||3.7%|
|Chondroitin sulfate only||5.3%||6.6%|
|Glucosamine HCL + chondroitin sulfate||6.5%||8.5%|
The scientists who conducted this study appropriately noted that only
three of the above changes were significant overall. Furthermore, for
the primary outcome in the combined glucosamine + chondroitin group, the
results were very close to reaching statistical significance. For the
secondary outcome, it did reach significance!
The media misinterpreted these findings and used them as ammunition to attack the efficacy of glucosamine and chondroitin supplements.
|Conflicts of Interest|
The New England Journal of Medicine recently enacted a policy of mandating disclosure of potential financial conflicts of interest amongst the authors of the studies it publishes. The reason for this was past instances of questionable articles supporting the safety-efficacy of drugs authored by doctors who were financially beholden to pharmaceutical companies that made the drugs.
What follows are the potential conflicts of the authors of the negative glucosamine study as reported by the New England Journal of Medicine:
"Drs. Bingham, Brandt, Clegg, Hooper, and Schnitzer report having received consulting fees or having served on advisory boards for McNeil Consumer and Specialty Pharmaceuticals. Drs. Brandt, Moskowitz, Schnitzer, and Schumacher report having received consulting fees or having served on advisory boards for Pfizer. Dr. Brandt reports having equity interests in Pfizer. Drs. Moskowitz and Weisman report having received lecture fees from Pfizer; Dr. Brandt, lecture fees from McNeil Consumer and Specialty Pharmaceuticals; Drs. Bingham, Clegg, Hooper, Jackson, Molitor, Sawitzke, and Schnitzer, grant support from Pfizer; and Dr. Bingham, grant support from McNeil Consumer and Specialty Pharmaceuticals. Dr. Brandt reports having received royalties from books related to osteoarthritis. Dr. Moskowitz reports having served as an expert consultant for Pfizer." - pp. 807 "Dr. Hochberg reports having received consulting fees from Pfizer and Merck and speaker's fees from Merck and Institut Biochimique." 59
Arthritis drugs are (or have been) huge moneymakers for the pharmaceutical companies. These same companies have paid monies to doctors who designed, oversaw, and authored the New England Journal of Medicine study and the negative editorial about glucosamine. Readers can make their own determination if this represents frank bias or, at a minimum, a disingenuous approach to scientific research.
The encouraging findings from the arthritis trial
As noted earlier, significant benefits were seen in patients with moderate to severe arthritis of the knee in the glucosamine-chondroitin group. Compared to placebo, the pain score percentage point improvements in the moderate to severe arthritis group were as follows: 59
|Therapy||Improvement in Primary Pain Score||Improvement in Secondary Pain Score|
|Glucosamine HCL only (note this is not glucosamine sulfate)||11.9%||17.1%|
|Chondroitin sulfate only||7.1%||10%|
|Glucosamine HCL + chondroitin sulfate||24.9%||26.4%|
Wrong form of glucosamine usedA troubling flaw in this study is that the wrong form of glucosamine was given to the study subjects. Glucosamine sulfate is the most prevalent form of glucosamine used in dietary supplements. Most of the studies showing significant efficacy used glucosamine sulfate, but the form used in the New England Journal of Medicine study was glucosamine hydrochloride.
Since the study subjects received glucosamine hydrochloride, they were not obtaining the joint-protecting benefits conferred by the sulfur found in the "sulfate" part of the glucosamine compound. The anti-arthritis benefits of sulfur are so well documented that many arthritis patients find relief with a low-cost supplement called MSM (methylsulfonylmethane), which is a concentrated source of sulfur. 62-72 The anti-arthritic properties of SAMe (s-adenosyl-methionine) are also thought to be related to its high sulfur content. 73-79
In this New England Journal of Medicine study that made headline news around the world, the subjects taking glucosamine only were getting no supplemental sulfur. Even the group getting the glucosamine and chondroitin was only getting a small amount of sulfur (from the chondroitin sulfate only).
Why the media attacked glucosamineIn an editorial appearing in the same issue of the New England Journal of Medicine, glucosamine was harshly criticized. It was obviously a lot easier for the media to echo one doctor's condemnation than to take the time to read the actual study itself.
This one doctor, by the way, receives consulting fees from Pfizer and Merck. In fact, a number of the authors of the glucosamine study published in the New England Journal of Medicine receive compensation from big pharma, mostly from Pfizer, which is the maker of Celebrex®. None of the study's authors had an economic interest in glucosamine or chondroitin. Some in alternative medicine have said this is equivalent to having an opposing team's referees dictate the outcome of a sporting event.
What most people don't realize, however, is that it is not the obligation of the media to provide accurate reporting. The media is responsible for generating profits for its shareholders, which means they have to grab the public's attention with sensational headlines that sell newspapers, TV viewing time, etc.
Reporting on the positive parts of the New England Journal of Medicine study would not have motivated many people to buy a newspaper. After all, there are dozens of studies substantiating the anti-arthritic properties of glucosamine sulfate and chondroitin sulfate. 59, 80-110 One more new study is hardly a newsworthy event.
There are now millions of Americans using glucosamine-based dietary supplements. These are the seventh most popular dietary supplement sold in the United States. There are over 20 million Americans affected by osteoarthritis. 111 So when the largest newspaper in the United States ran the headline, "Two Arthritis Drugs Found To Be Ineffective," they knew it would catch a lot of attention. The fact that glucosamine and chondroitin were labeled as "drugs" is an indication of how little time this newspaper spent evaluating the actual study.
How effective is glucosamine-chondroitin?In previous issues of Life Extension magazine, we have discussed the studies indicating a significant benefit to arthritic patients who take glucosamine sulfate and chondroitin sulfate. 112-113 It is because of these successful earlier studies that this latest study published in the New England Journal of Medicine was conducted.
While glucosamine-chondroitin have documented efficacy, many arthritis sufferers need to take a broader approach to relieving inflammation, immobility, and chronic pain. Fish oil, for instance, has been shown to help reduce pro-inflammatory eicosanoids such as prostaglandin E2 and leukotriene B4, along with pro-inflammatory cytokines such as TNF-alpha and IL-1b. 114-116 These inflammatory factors play a major role in degenerative joint disease. Over the past 10 years, we have published findings showing benefits when combinations of fish oil, borage oil, glucosamine, and other nutrients are taken together. 117
|Sulfur for the Joints|
One of the flaws in the New England Journal of Medicine study may have been that the form of glucosamine used did not provide any sulfur.
Animal studies have shown that joints affected by osteoarthritis have lower sulfur content, 118 and that arthritic mice given a sulfur-containing nutrient (MSM) experience less joint degeneration. 119 In a double-blind trial in people with osteoarthritis, study participants who received MSM by itself experienced significant pain relief. 120
In a study published in 2004, the combination of glucosamine with MSM was found to more effective in improving the signs and symptoms of osteoarthritis than either agent alone. 62 After 12 weeks of treatment, the average pain score in the glucosamine-only group dropped from 1.74 to 0.65.a 63% reduction. In the MSM-only group, it fell from 1.53 to 0.74...a 52% reduction. However, in the group taking glucosamine and MSM, the average pain score dropped from 1.7 to 0.36.an astounding reduction of 79%! The researchers also found that the combination therapy had a faster effect on pain and inflammation than either glucosamine or MSM alone.
It is important to point out, however, that some studies have used glucosamine HCL to effectively relieve arthritis pain.
Media tries to bury saw palmettoMore than 20 published studies show that saw palmetto alleviates symptoms associated with benign prostate disease such as frequent urination, low urine stream, and a feeling of not completely emptying the bladder. 121-141
A recent study however, found saw palmetto to be ineffective in men with moderate-to-severe benign prostate hypertrophy. As a result of this one study, the media declared saw palmetto useless.
The doctors who conducted this negative saw palmetto study received financial compensation from Merck (which makes Proscar®), GlaxoSmithKline (which makes Avodart®), and TAP Pharmaceuticals (which makes Lupron®). Proscar and Avodart are drugs that directly compete against saw palmetto, whereas Lupron is used mostly by men who develop prostate cancer.
Some in the alternative medical community have cried "foul," in as much as the doctors overseeing this negative saw palmetto study received financial compensation from the same pharmaceutical companies that stood to gain the most from discrediting non-prescription herbal therapies such as saw palmetto.
Flaws in saw palmetto study
One of the defects of the negative saw palmetto study is that it evaluated men who had more advanced prostate disease than did most of the participants in the favorable saw palmetto studies. In the numerous European studies that documented saw palmetto's efficacy, most of the men evaluated were considered to have moderate prostate disease. The study used to attack saw palmetto, on the other hand, looked at men with moderate-to-severe prostate disease. Researchers long ago determined that men with moderate-to-severe benign prostate disease need aggressive therapy to achieve effective relief. This is why recent studies showing positive benefit to herbal prostate remedies have used saw palmetto combined with nettle root. 142-146 This fact raises questions as to why so much money was spent funding a study of men with significant prostate disease using only saw palmetto, when European doctors prescribe combination herbal therapies to treat benign prostate disease.
Another flaw of this study is that the group assigned the saw palmetto had more pronounced prostate disease than did the placebo group. For instance, the group receiving saw palmetto had a BPH Impact Score that was statistically significantly worse than the placebo group at baseline. Whether these baseline differences had an impact on the study's outcome is unknown. By placing men with more severe prostate disease in the saw palmetto group, however, the study was biased against saw palmetto from the beginning.
|The Overlooked Effects of Estrogen on the Prostate|
|Mainstream medicine remains fixated on the role of testosterone
and dihydrotestosterone in promoting prostate gland overgrowth. Prostate
disease, however, does not strike young men with high testosterone
The overlooked fact is that as men grow older, they produce less testosterone and a lot more estrogen. Prostate cells contain estrogen receptor sites, demonstrating that the gland can respond directly to the growth-promoting effects of estrogen. Recent data suggest that estrogens play a role in prostate disease. 147-149
Aging men, in particular those with the so-called pot belly (abdominal obesity), often have excess levels of the aromatase enzyme that converts testosterone into estrogen. The prostate itself expresses aromatase that can convert testosterone into estrogen within the gland itself. Two herbal extracts used extensively in Europe (pygeum and nettle root) have demonstrated aromatase-suppressing effects in vitro, especially when they are used together. 150
Why this study is irrelevant to aging men todayEuropean doctors use various combinations of pygeum, nettle root, beta-sitosterol, saw palmetto, and other herbs to treat benign prostate disease. Despite numerous scientific studies indicating that treatment of prostate enlargement should include a combination of herbal extracts, the doctors who designed the one recent negative study choose to test saw palmetto in isolation.
Based on evidence that prostate disease is caused by several different factors, it would appear that the recent study that used only saw palmetto to treat men with moderate-to-severe prostate disease was designed to fail. The study therefore has no relevance to men taking combination supplements that provide nettle root (Urtica dioica), pygeum, beta-sitosterol, and other plant extracts that have proven efficacy in dozens of published scientific studies. 151-181
It is important to also note that this is only one study of a relatively small group of men with moderate-to-severe prostate enlargement who were only allowed to use saw palmetto. Ten times as many men with varying degrees of prostate disease have participated in other studies that showed even saw palmetto taken by itself to be highly effective. 121-141
Exposing the recent media attack against dietary supplements
Over the past several months, the media has questioned the efficacy of several popular dietary supplements. In the upcoming June 2006 issue of Life Extension magazine, we dissect these negative media reports down to the bone to reveal the hard scientific facts.
In doing so, we expose the absurdity of the headline-hungry media making proclamations such as "another natural remedy bit the dust" when describing the recent glucosamine study. We also reveal the inappropriateness of conventional doctors, with little knowledge about the proper use of nutrients, but with strong financial ties to the pharmaceutical industry, conducting studies that contain so many flaws that their findings are largely irrelevant.
Members of the Life Extension Foundation discover the science behind the headlines in order to avoid being victimized by the medical establishment's ominous propaganda machine.
For longer life,
P.S.- At the beginning of this letter, I stated that the front page of the Wall Street Journal featured an article stating:
"Design problems in all the trials means the results don't really answer the questions they were supposed to address. And a flawed communications effort led to widespread misinterpretation of the results by the news media and the public." 1
It is important to note that like other media outlets, the Wall Street Journal (in other articles) regurgitated the same negative reports about dietary supplements as did the New York Times, Washington Post, Associated Press, et al.
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