Melanoma is a cancer of the neural crest-derived cells that provide pigmentation to skin and other tissues. Over the past 4 decades, the incidence of melanoma has increased more rapidly than that of any other malignancy in the United States. The National Cancer Institute reports a 2 percent increase in the incidence of melanoma between 1992 and 2002. New melanoma cases are diagnosed in about 60,000 people each year in the United States, and almost 8,000 die because of metastasized melanoma. Although melanoma accounts for only 4 percent of all dermatologic cancers, it is responsible for 80 percent of deaths from skin cancer; only 14 percent of patients with metastatic melanoma survive for five years. It can return years or decades later in 10 percent of patients who had already been treated.
Natural remedies for melanoma
treatment of prevention
Research with vitamins or supplements for melanoma prevention or treatment is still very new, therefore no statements can be made with any confidence. However, it is interesting to point out that certain herbs or supplements have anti melanoma activity in test tubes. Here are some options that you can discuss with your doctor:
Curcumin is an extract from turmeric spice, natural curcumin supplements are available as capsule over the counter.
Cordyceps is a mushroom, orally administered cordycepin inhibits melanoma cell growth in mice with no adverse effects.
Garlic should certainly be tried for this condition.
Green tea extract has a potent extract EGCG, which is becoming very popular
Melatonin has been studied, it is a pineal hormone.
Mistletoe herb has lectins which kill cancer cells.
Quercetin is a flavonoid
Rosemary extract contains carnosol, a constant constituent of Rosmarinus officinalis extracts, is a phenolic diterpene shown to have antioxidant and anticarcinogen properties.
Resveratrol found in skin of grapes
Tea tree oil, terpinen-4-ol, the main component of Melaleuca alternifolia, inhibits the in vitro growth of human melanoma cells.
Q. I was recently diagnosed with melanoma skin cancer. It
seems to have developed out of an existing mole. I have more than 100 moles on
my body. I am very concerned about more of them turning to melanoma. Could you
please suggest herbal supplements that may be good to take?
A. The above may be considered but I am not aware of human studies that show their use will be effective. But I am hopeful.
Curry ingredient fights skin
The compound that makes curry yellow could help fight skin cancer. Curcumin, found in the spice turmeric, interferes with melanoma cells. Tests in laboratory dishes show that curcumin made melanoma skin cancer cells more likely to self-destruct in a process known as apoptosis. The same research team has found that curcumin helped stop the spread of breast cancer tumor cells to the lungs of mice. The curcumin suppressed two proteins that tumor cells use to keep themselves immortal. People who eat plenty of turmeric have lower rates of some cancers.
Curcumin -induced antiproliferative and proapoptotic effects in melanoma cells
are associated with suppression of IkappaB kinase and nuclear factor kappaB
activity and are independent of the B-Raf/mitogen-activated/extracellular
signal-regulated protein kinase pathway and the Akt pathway.
Nuclear factor-kappaB plays a central role in cell survival and proliferation in human melanoma. Curcumin has potent antiproliferative and proapoptotic effects in melanoma cells. These effects were associated with the suppression of NF-kappaB and IKK activities but were independent of the B-Raf/MEK/ERK and Akt pathways.
Immunopharmacol Immunotoxicol. 2010; Cytotoxic effect of garlic extract and its fractions on Sk-mel3 melanoma cell line. Department of Science and Research, Islamic Azad University, Tehran, I.R. Iran.
Historically, plants have been main resources in traditional medicine and natural products are considered as important sources of antitumor drugs. Meanwhile, garlic for a long time has been used in man's food as a medicinal plant. In this study, the garlic extracts induceded a significant cytotoxic activity on Sk-mel3 cell line. Garlic appears to be a good candidate as an antitumor agent against melanoma.
Role of melatonin
Melatonin decreases cell proliferation and induces melanogenesis in human melanoma SK-MEL-1 cells.
J Pineal Res. 2010.
Melatonin is an indoleamine synthesized in the pineal gland, and after its release into the blood, it has an extensive repertoire of biological activities, including antitumoral properties. In this study, we found that melatonin reduced the growth of the human melanoma cells SK-MEL-1. The antiproliferative effect was associated with an alteration in the progression of the phases of the cell cycle and also with an increase in tyrosinase activity, the key regulatory enzyme of melanogenesis.
Int J Vitam Nutr Res. 2013. Association between dietary vitamin C and risk of cutaneous melanoma in a population of Northern Italy. Results suggest a possible protective activity of vitamin C intake against cutaneous melanoma in specific subgroups of this population of Northern Italy.
Dermatoendocrinol. 2013. Vitamin D and melanoma. Recreational sun exposure and sunburn are causal for melanoma but the risk is strongly genetically determined. Health promotion advice about sun protection should be aimed at susceptible individuals (pale skin, freckles, large numbers of melanocytic nevi and a family history). We discuss here the evidence that sun-sensitive people have lower vitamin D levels and that, in practice, it is very difficult for such individuals to achieve sufficient levels without supplementation in the UK at least. We conclude that melanoma susceptible sun-avoidant individuals should be advised to avoid insufficiency by supplementation. Vitamin D is anti-proliferative in vitro for some melanoma cell lines. In a large melanoma cohort we have observed that lower serum 25-hydroxyvitamin D2/D3 levels at diagnosis were associated with thicker tumors and poorer prognosis (study as yet not validated). In the UK, melanoma patients commonly have sub-optimal 25-hydroxyvitamin D2/D3 levels at and post diagnosis;
Melanoma symptom and sign
Often, the first sign of melanoma is a change in the size, shape, color, or feel of an existing mole. Most melanomas have a black or blue-black area. Melanoma also may appear as a new, black, abnormal, or "ugly-looking" mole. Eye melanoma or ocular melanoma can also occur.
Melanoma is much deadlier when it appears on the scalp or neck than somewhere else on the body.
No current treatments substantially enhance patient survival once melanoma metastasis has occurred. Except for high-dose interferon as adjuvant therapy in stage III disease, little success has emerged over the last 20 years for metastatic melanoma. Besides operative therapy, which is the only effective treatment for malignant melanoma, postoperative adjuvant chemotherapy, immunotherapy, radiotherapy, and biologic therapy also are of great importance. In recent years, immunologic strategies including tumor vaccine and adjuvant therapy with interferon-alfa have been attempted to improve survival of patients with more advanced malignant melanoma.
Melanoma survival rate or prognosis depends often on the severity of the melanoma and whether metastasis has occurred. Some people with melanoma are at increased risk of developing the skin cancer again in the future, especially if they have a family history of the disease.
The recently approved drug vemurafenib (Zelboraf) has been hailed as a breakthrough in treatment. But roughly one-quarter of patients who take the medication develop a troublesome side effect: secondary skin cancers called squamous cell carcinomas.
Drugs Today 2013. Dabrafenib in the treatment of advanced melanoma.
Melanoma risk from medication
Patients with rheumatoid arthritis who are treated with methotrexate may have an elevated risk of developing melanoma compared with the general population.
There are 4 major types of melanoma:
* Superficial spreading melanoma is the most common type of melanoma. It is usually flat and irregular in shape and color, with varying shades of black and brown. Superficial spreading melanoma may occur at any age or site and is most common in Caucasians.
* Nodular melanoma usually starts as a raised area that is dark blackish-blue or bluish-red, although some lack color.
* Lentigo maligna melanoma usually occurs in the elderly. Lentigo melanoma is most common in sun-damaged skin on the face, neck, and arms. The abnormal skin areas are usually large, flat, and tan with intermixed areas of brown.
* Acral lentiginous melanoma is the least common form of melanoma. It usually occurs on the palms, soles, or under the nails and is more common in African Americans.
Risk of Melanoma with Skin Cancer
Women who've had common, highly curable forms of skin cancer may face a heightened risk of the deadlier skin tumor melanoma. A study of more than 67,000 white postmenopausal women found that those with a history of non- melanoma skin cancer were 70 percent more likely than other women to develop melanoma during the study period. The findings suggest that there are genetic influences that make some people vulnerable to both melanoma and non- melanoma skin cancers. Two forms of non-melanoma skin cancer -- basal cell and squamous cell -- account for the large majority of skin cancer cases, and are rarely fatal themselves. Based on the new findings, though, the diseases can be added to the list of risk factors for the deadlier melanoma. The results are based on data from the Women's Health Initiative, a large study of U.S. women begun in 1994 that collected detailed health and lifestyle information and followed up with participants annually. Women with a history of non- melanoma skin cancer should thorough skin examinations at frequent intervals to catch any new lesions early. Cancer, February 1, 2006.
Marathon runners may face an increased risk of skin cancer, Austrian researchers report. Based on the findings, they conclude, long-distance runners should make an effort to reduce their exposure to ultraviolet (UV) radiation by using sunscreen, wearing protective clothing, and organizing their training and competition routines accordingly. Dr. Christina M. Ambros-Rudolph of the Medical University of Graz in Austria and colleagues decided to investigate melanoma risk among long-distance runners after treating eight ultramarathon runners with the disease over a 10-year period. Along with sun exposure, immunosuppression due to intense training has been proposed as a potential trigger for melanoma. They recruited 210 marathon runners ranging in age from 19 to 71 years for the study, matching them by age and sex with a control group of non-marathoners. Even though men and women in the control group had more signs of sun sensitivity, such as light eye and skin color and more birthmarks, the marathoners were more likely to have changes in the skin that signal an increased malignant melanoma risk.
People who use tanning beds do not protect themselves from skin damage from subsequent sun exposure. In fact, use of sunbeds before age 35 substantially increases the risk of developing melanoma. More women than men visit tanning salons and their rate of the skin condition is increasing.
Sun-filled family vacations can leave children with more moles on their skin. These moles, also known as melanocytic nevi, are a precursor of melanoma.
People with Parkinson's disease face an increased risk of the most deadly type of skin cancer. Archives of Neurology, March 2010.
Another melanoma risk?
Infants with hyperbilirubinemia who are treated with intensive phototherapy, the current standard treatment, have a significantly increased risk of melanocytic nevi. Given the link between such nevi and melanoma, dermatologic surveillance and preventive measures are important for these children. Archives Dermatolology 2006;142:1599-1604.
Genetics and family history
Having an identical twin with melanoma increases a person's own risk of the disease nearly 10-fold, while melanoma associated with having a non-identical twin with the disease is roughly doubled.
Melanoma skin cancer is becoming more common among Hispanics and whites. Among blacks and Hispanics, melanoma is likely to be diagnosed at a more advanced stage. White people, particularly those with fair skin, have the highest rates of melanoma -- the least common but most deadly form of skin cancer. Archives of Dermatology, December 2009.
Melanoma survivors are at increased risk of other cancers as well as the return of their skin cancers. The most common second cancers after melanoma are breast, prostate, and non-Hodgkin's lymphoma. Archives of Dermatology, 2010.
Rapid growth of melanoma
Rapidly growing cutaneous melanomas exhibit a number of identifying characteristics including color and shape. Because of their rapid growth there is only a small window of opportunity to capture these melanomas in their early stage of development. Rapidly growing melanomas can occur in anyone, not necessarily those with large numbers of moles and freckles. In fact, they more often occur in those without large numbers of moles and freckles, and elderly men. Morphologically, they are more often red -- rather than brown and black -- symmetrical, elevated and symptomatic. Archives Dermatology 2006;142.
Cancer in Australia
Australia has the highest skin cancer rate in the world and despite decades of health campaigning the rate of melanoma, which is the most common kind of cancer, is soaring. The melanoma rate rose 12 percent in men and 15 percent in women in the last 10 years, and is expected to rise another 11 percent by 2011.
The increase in rates of melanoma, the most dangerous type of skin cancer, in the United States in recent years may reflect heightened diagnostic scrutiny rather than a true increase in new cases.
However, the annual rate of occurrence of new melanomas in children in the United States is increasing rapidly.
Patients with metastatic melanoma (MM) have new hope, says a published study by Mayo Clinic Cancer Center. The study, showed the combination of paclitaxel and carboplatin (PC) appears to be effective for metastatic melanoma when traditional treatments have failed.
Melanoma Diagnosis in Blacks
Melanoma is diagnosed at a late stage more commonly among darker skinned individuals than in white patients. There are two broad possibilities for this. It's possible that melanoma is a faster, more aggressive disease in non-whites than whites; or, more likely, is a lack of education among patients and physicians. Black and hispanic patients at high risk are known to lack education about the disease and to engage in fewer self-protective behaviors, such as putting on sunscreen and staying out of the bright sun.
Statins and Melanama
Although there was thought to be an association between use of cholesterol-lowering statins and fibrates and a reduced risk of melanoma, a meta-analyses of trials of such drugs does not bear out this apparent connection.
Melanoma diagnosis from hair
Measuring the amount of melanin in a hair sample independently predicts an individual's risk for melanoma. Melanin is a natural substance that gives color to the hair, skin and iris of the eye, and also protects the skin from damaging rays of the sun. Determining the amount of melanin as an indication of an individual's skin type could be used to advise patients how often they should be screened for skin cancer and to also provide individualized patient advice. Hair concentrations of melanin can be measured by various means. Measuring 2,3,5-pyrroletricarboxylic acid (PTCA) levels, which forms after the oxidation of the pigment eumelanin, provides the strongest results. Subjects with a PTCA concentration below 85 ng/mg have more than four times the risk of developing melanoma. American Journal of Epidemiology, May 15, 2007.
Melanoma and Parkinson's
A family history of melanoma seems to be tied to a genetic susceptibility to develop Parkinson's disease.
Melanoma Cancer Research
Low plasma coenzyme Q10 levels as an independent prognostic factor for melanoma progression.
J Am Acad Dermatol. 2006. Department of Dermatology, Catholic University of the Sacred Heart, Rome, Italy.
Abnormally low plasma levels of coenzyme Q10 have been found in patients with cancer of the breast, lung, or pancreas. A prospective study of patients with melanoma was conducted to assess the usefulness of CoQ10 plasma levels in predicting the risk of metastasis and the duration of the metastasis-free interval. CONCLUSIONS: Analysis of our findings suggests that baseline plasma CoQ10 levels are a powerful and independent prognostic factor that can be used to estimate the risk for melanoma progression.
Protective effect of quercetin and luteolin in human melanoma HMB-2 cells.
Mutat Res. 2005.
Multifunctional effects of flavonoids are reported to be markedly connected with their structure and the functional groups in the molecule. The important role in the activity play C2-C3 double bond, hydroxyl group at C3 and the number of hydroxyl groups at phenyl ring (B). In this paper, the DNA protective free radical scavenging potential of quercetin (QU) and luteolin (LU) against H2O2 and their clastogenic effect alone and in combination with melphalan (MH) were investigated in human melanoma HMB-2 cells. Elevated frequency of chromosomal aberrations induced by MH, that at high doses have shown a variety of toxic side effects, was statistically decreased by studied flavonoids regarding to control (QU at the concentration of 50 microM and LU already at the concentration of 20 microM). The results concerning DNA protective potential against free radicals in HMB-2 cells demonstrated that QU and LU have significant effect in dose dependent manner. The percentage of QU protective effect is 40% at the concentration 20 microM, resp. 80% at the concentration 100 microM. Comparable values were obtained with LU. Results are correlated to their structural arrangement and organization of the hydroxyl groups.
Anti-proliferative and proapoptotic effects of (-)-epigallocatechin-3-gallate
on human melanoma: possible implications for the chemoprevention of melanoma.
Int J Cancer. 2005.
Melanoma accounts for only about 4% of all skin cancer cases but most of skin cancer-related deaths. Standard systemic therapies such as interferon (IFN) have not been adequately effective in the management of melanoma. Therefore, novel approaches are needed for prevention and treatment of this disease. Chemoprevention by naturally occurring agents present in food and beverages has shown benefits in certain cancers including nonmelanoma skin cancers. Here, employing 2 human melanoma cell lines (A-375 amelanotic malignant melanoma and Hs-294T metastatic melanoma) and normal human epidermal melanocytes (NHEM), we studied the antiproliferative effects of epigallocatechin-3-gallate (EGCG), the major polyphenolic antioxidant present in green tea. EGCG treatment was found to result in a dose-dependent decrease in the viability and growth of both melanoma cell lines. Interestingly, at similar EGCG concentrations, the normal melanocytes were not affected. EGCG treatment of the melanoma cell lines resulted in decreased cell proliferation (as assessed by Ki-67 and PCNA protein levels) and induction of apoptosis (as assessed cleavage of PARP, TUNEL assay and JC-1 assay). EGCG also significantly inhibited the colony formation ability of the melanoma cells studied. EGCG treatment of melanoma cells resulted in a downmodulation of anti-apoptotic protein Bcl2, upregulation of proapoptotic Bax and activation of caspases -3, -7 and -9. Furthermore, our data demonstrated that EGCG treatment resulted in a significant, dose-dependent decrease in cyclin D1 and cdk2 protein levels and induction of cyclin kinase inhibitors (ckis) p16INK4a, p21WAF1/CIP1 and p27KIP1. Our data suggest that EGCG causes significant induction of cell cycle arrest and apoptosis of melanoma cells that is mediated via modulations in the cki-cyclin-cdk network and Bcl2 family proteins. Thus, EGCG, alone or in conjunction with current therapies, could be useful for the management of melanoma.
Dietary supplementation with high-selenium soy protein reduces pulmonary
metastasis of melanoma cells in mice.
J Nutr. 2004.
The effect of high-selenium (Se) soy protein on pulmonary metastasis of murine B16BL6 melanoma cells was investigated in male C57BL6 mice. Isolated soy proteins (ISP) from soybeans grown with and without Se foliar application during seed development were compared. We conclude that the high-Se soy protein has a greater inhibitory effect than the low-Se soy protein on pulmonary metastasis of melanoma cells in mice.
[Retrospective study of malignant melanoma patients treated with mistletoe
Forsch Komplementarmed Klass Naturheilkd. 2003.
The aim of the present investigation was to analyze survival time and survival rate of all patients with malignant melanoma who had been counseled at the Tumorambulanz Herdecke of the Community Hospital Herdecke. 284 melanoma patients were included in a retrospective questionnaire study. Only those patients were considered for analysis in whom the prognostic factors histology, tumor localization, and Clark level were known. The data of the study population were compared with patient data obtained from the literature. 94 patients were included in the analysis. 66 of whom had received and 7 had not received mistletoe treatment, in the remaining 21 patients there was no information whether or not mistletoe treatment had been given. Thus, we did our study without a clearly defined internal control group. The median survival time among patients treated with mistletoe had been 14.1 years. The 5- and 10-year survival rates were 80 and 68% for the mistletoe-treated patients, respectively. The 5-year survival rate of the mistletoe-treated patients is comparable to that of patients without mistletoe therapy while the 10-year survival rate is a little bit lower. This may be due to the fact that, in contrast to the patients from the relevant literature, 33% of the patients suffered from lymph node and/or distant metastases already before counseling the Tumorambulanz Herdecke. Moreover, 50% of our patients had melanoma of Clark level IV in contrast to 22% or 31% in the relevant literature. In spite of the theoretical reservations against mistletoe treatment in melanoma patients, our retrospective analysis did not show any clues about disadvantages of mistletoe treatment in melanoma patients. A controlled prospective study therefore should prove the efficacy of a mistletoe therapy in patients with malignant melanoma.
Tanning beds and melanoma
Dr. George Hollenberg, M.D., a New York-area pathologist and founder of Acupath Laboratories says: "Young Americans are frequenting tanning salons at the brisk rate of 1 million visits per day. Researchers have confirmed that the long-term results are anything but healthy. A study published in the March 2007 issue of the International Journal of Cancer found that tanning bed use before age 35 increases the risk of developing melanoma, the deadliest form of skin cancer, by up to 75 percent. The most significant known risk factor for melanoma cancer is unprotected exposure of the skin to ultraviolet light -- essentially, the modus operandi of a tanning bed -- which makes the link between the two hardly surprising." Dr. George Hollenberg, M.D. is an authority in the fields of pathology, clinical pathology and dermatopathology with expertise in the areas of dysplastic nevi, melanoma, prostate and gastrointestinal cancer. Board-certified in Pathology and Dermatopathology, Dr. Hollenberg is a Fellow of the College of American Pathologists, The American Society of Dermatopathology and the AMA.
Patients with metastatic melanoma have new hope: the combination of paclitaxel and carboplatin appears to be effective for metastatic melanoma when traditional treatments have failed.
Q. I was wondering if you might review the information on melanoma at your site and consider adding some information that has stirred controversy, but may be life-saving. While early sunburns appear to correlate with a higher
risk, there is evidence that vitamin D deficiency is a factor later on. The research that you referenced in your article about melanoma indicates that those who have had other types of skin cancer seem to be at higher risk of melanoma.
Could it be that, in accordance with their dermatologist's recommendations, they are using sunscreens more judiciously (which block vitamin D production by over 95% even at low SPFs), and have unwittingly increased melanoma incidence and recurrence? Because of this type of research, I am concerned that people with risk will get the impression that ideally they should avoid the sun entirely. I have been reading with great interest Dr. Michael
Holick's work at Boston University. A short article referencing highlights is at:
It just seems a little too coincidental to me that melanoma has been increasing, even as judicious use of sunscreen has also been increasing. Since we already know that many cancers, cardiovascular disease, diabetes, MS, and possibly autism (decreased activated vitamin D in brain) seem to be hindered/prevented by adequate vitamin D levels, it would seem to be a safe recommendation, if not a life-saving measure, to prescribe at least some unprotected sunshine exposure and vitamin D supplementation for those with skin cancer risk, especially melanoma. I can also see a potential problem for someone who has melanoma risk and who has been placed on a statin drug..... I would like to see a research study analyzing data to see if manipulation of this increases risk for melanoma, or other conditions
typically resulting from vitamin D deficiency. Thank-you for your informative website. I visit often.
A. There are many factors involved in melanoma formation including genetics, early life heavy sun exposure, diet, smoking, use of sunscreens, skin color, latitude and country where the person lives, atmospheric changes over time on this planet, etc. It is possible that vitamin D deficiency may be an additional factor and this would be an interesting topic for research.
Q. I am aware of the various risk factors that have been named as probable. In fact, the latitude and country / location factors you mentioned may directly relate to the vitamin D issue, as they have already connected this with M.S. However, I was referring to a specific statement at the web site that folks that have had other types of skin cancer are at greater risk for melanoma. My comment about this observation is that since people who have had basal cell or squamous cell cancers are the same people who most avoid the sun, use the most sunscreen and so are at great risk for vitamin D deficiency -- and since we already know that vitamin D deficiency increases melanoma occurrence and
recurrence -- I was asking if Dr. Sahelian would consider mentioning this and suggesting that these folks be extra diligent in supplementing their vitamin D accordingly (that they at least have their levels tested), since vitamin D deficiency in this group is almost certain. It might also protect this subpopulation from other cancers, as well, and improve their risk with respect to cardiovascular disease and diabetes.
Q. Are the herbs and
ashwagandha herb, tongkat
ali herb, or saw palmetto
helpful in melanoma?
A. I have not seen any studies regarding these herbs and their influence on melanoma.
Q. In completing research on tyrosine supplement I came
across a reference to melanoma skin cancer. The reference stated that
individuals with melanoma should not take L-Tyrosine. Is this a valid statement
with some basis in fact?
A. We have not seen any research that would support the viewpoint that tyrosine supplement use has harmful effects on melanoma.
Q. Dr. Sahelian, since your website carries a page which carries natural therapies recommendations specifically for melanoma I thought you might want to update it with information on the natural compound Avemar, since recently published results of a clinical trial showed very promising results. Demidov LV, Manziuk LV, Kharkevitch GY, Pirogova NA, Artamonova EV, Adjuvant fermented wheat germ extract (Avemar) nutraceutical improves survival of high-risk skin melanoma patients: a randomized, pilot, phase II clinical study with a 7-year follow-up, Cancer Biother Radiopharm. 2008. The fermented wheat germ extract (FWGE) nutraceutical Avemar, manufactured under "good manufacturing practice" conditions and, fulfilling the self-affirmed "generally recognized as safe" status in the United States, has been approved as a "dietary food for special medical purposes for cancer patients" in Europe. In this paper, we report the adjuvant use of this nutraceutical in the treatment of high-risk skin melanoma patients. In a randomized, pilot, phase II clinical trial, the efficacy of dacarbazine (DTIC)-based adjuvant chemotherapy on survival parameters of melanoma patients was compared to that of the same treatment supplemented with a 1-year long administration of FWGE. At the end of an additional 7-year-long follow-up period, log-rank analyses showed significant differences in both progression-free (PFS) and overall survival (OS) in favor of the FWGE group. Mean PFS: 55 months (FWGE group) versus 29 months (control group). Mean OS: 66 months (FWGE group) versus 44 months (control group). The inclusion of Avemar into the adjuvant protocols of high-risk skin melanoma patients is highly recommended. You and I have met at various natural medicine and natural product industry trade shows. My company markets Ave’ the first dietary supplement to contain the proprietary nutritional ingredient Avemar, which is made by the fermentation of wheat germ by baker's yeast through a patented process. It is standardized on the compound DMBQ (di-methoxy-substituted benzoquinones), and has been the subject of close to 100 studies in cell lines and with animal and human subjects resulting in more than 20 articles in peer-reviewed medical journals, showing that it helps regulate cell metabolism, inhibiting non-oxidative and enhancing oxidative glucose metabolism, and support many mechanisms of immune system regulation. Studies are available by searching PubMed with the search terms Avemar and/or "fermented wheat germ."