In the News

The importance of conducting proper research to prove safe and effective medical uses for the active chemicals in marijuana and its components

Greater Levels of Vitamin D Associated with Decreasing Risk of Breast Cancer

Kids’ Fracture Risk & K2 deficiency Linked in Recent Study

Children's Fluoride Exposures Linked to Later Life Disease?

Life Extension® clinical study finds KaempMax™, a Kaempferia parviflora ethanol extract, enhances male sexual health

The importance of conducting proper research to prove safe and effective medical uses for the active chemicals in marijuana and its components

Statement by FDA Commissioner Scott Gottlieb, M.D.

Over the past decade, we’ve seen a growing interest in the development of therapies derived from marijuana and its components. Proponents of “medical marijuana” advertised its uses for a wide number of medical conditions, such as cancer, multiple sclerosis, post-traumatic stress disorder and anxiety – just to name a few of the touted conditions. The FDA has been supportive of research in this area for many years. But marijuana is a Schedule I compound with known risks. Research to demonstrate that marijuana or its components could be safe and effective in the treatment of medical disorders should be held to the same standard as other drug compounds. And certainly it should not be held to a lower standard, as some proponents would suggest. The FDA has an active program to assist drug developers who want to investigate marijuana or its components through properly controlled clinical trials, to demonstrate the potential for safe and effective uses.

Today, the FDA approved a purified form of the drug cannabidiol (CBD). This is one of more than 80 active chemicals in marijuana. The new product was approved to treat seizures associated with two rare, severe forms of epilepsy in patients two years of age and older.

This product approval demonstrates that advancing sound scientific research to investigate ingredients derived from marijuana can lead to important therapies. This new treatment provides new options for patients.

This is an important medical advance. But it’s also important to note that this is not an approval of marijuana or all of its components. This is the approval of one specific CBD medication for a specific use. And it was based on well-controlled clinical trials evaluating the use of this compound in the treatment of a specific condition. Moreover, this is a purified form of CBD. It’s being delivered to patients in a reliable dosage form and through a reproducible route of delivery to ensure that patients derive the anticipated benefits. This is how sound medical science is advanced.

So today, in addition to celebrating this scientific achievement and the medical advance that it represents for these patients and their families, we should also reflect on the path that made this possible. It’s a path that’s available to other product developers who want to bring forth marijuana-derived products through appropriate drug development programs.

That pathway includes a robust clinical development program, along with careful review through the FDA’s drug approval process. This is the most appropriate way to bring these treatments to patients. This process also includes a review of the purity of a new drug and manufacturing controls. Before a high-quality drug can be developed, evaluated, and eventually approved by the FDA; it’s critical that the necessary work is done to identify drugs of potential medical benefit and conduct rigorous scientific research through adequate and well-controlled clinical trials. This is true for all drugs, including ones derived from plant materials, like marijuana. And the FDA remains committed to collaborating with federal and state agencies, researchers and product developers on advancing this type of important and conscientious work.

This research process – from early development through preclinical and clinical research – gives us a comprehensive understanding of a new drug. That includes an understanding of whether the new product is safe and effective for treating a particular medical condition, what the proper dosage is and for what populations it is safe and effective, how the new compound could interact with other drugs, or whether the new drug has side effects or other safety concerns.

This work also helps product developers identify the appropriate dosage needed to achieve the desired therapeutic effect while minimizing toxicity and risk. Taken in totality, the scientific evidence generated by these studies forms the basis of the FDA’s evaluation of benefit versus risk. And it’s because of this careful, scientific and evidence-based evaluation by the FDA that health care providers can rely on having a quality product that delivers a consistent, uniform dose of an effective medication that is able to deliver a predictable treatment to patients. This is especially important when considering treatment for serious medical conditions that will be utilized in the clinical care of patients who may have any number of health vulnerabilities. The purified form of the drug CBD approved today by the FDA has been shown to meet these rigorous standards.

Research on the therapeutic effects of marijuana and its components involves a number of federal agencies in addition to the FDA, including the National Institute on Drug Abuse, part of the National Institutes of Health, and the Drug Enforcement Administration. 

The FDA has taken several specific steps to support this research.

We meet regularly with researchers as they plan and carry out their trials. We have also formed a Botanicals Team that provides scientific expertise on botanical issues for researchers developing drugs derived from plants, such as marijuana. That team published guidance for industry on clinical studies involving botanical drugs, as well as quality controls for lot-to-lot consistency. In recent years, the agency also has recommended to the DEA the approval of several hundred Schedule I research protocol licenses for research on marijuana or its constituent compounds.

Additionally, the FDA also works with companies to provide patients access to experimental therapies while clinical trials are ongoing through expanded access provisions. These approaches help protect patients while also allowing for the collection of data necessary to support the FDA approval of safe and effective therapies for use in the broader population. Through this process, hundreds of children were able to get access to investigational CBD products while this product was being studied.

Drugs derived from marijuana also are eligible for several programs that are intended to facilitate and expedite development and review of new drugs that address unmet medical needs in the treatment of serious or life-threatening conditions. Much of the work we’ve done to encourage research in this area has led to the approval action we took today.

The FDA will continue to support rigorous scientific research on potential medical treatments using marijuana and its components that seek to be developed through the appropriate scientific channels. However, we remain concerned about the proliferation and illegal marketing of unapproved CBD-containing products with unproven medical claims.

The promotion and use of these unapproved products may keep some patients from accessing appropriate, recognized therapies to treat serious and even fatal diseases. The FDA has taken recent actions against companies distributing unapproved CBD products. These products have been marketed in a variety of formulations, such as oil drops, capsules, syrups, teas, and topical lotions and creams. These companies have claimed that various CBD products could be used to treat or cure serious diseases such as cancer with no scientific evidence to support such claims. We’ll continue to take action when we see the illegal marketing of CBD-containing products with unproven medical claims. We’re especially concerned when these products are marketed for serious or life threatening diseases, where the illegal promotion of an unproven compound could discourage a patient from seeking other therapies that have proven benefits.

Today’s approval demonstrates our commitment to the scientific process and working with product developers to bring marijuana-based products to market. We remain committed to our gold standard for product development and review. Such a process ensures that any new therapies from marijuana and its constituents are safe, effective and manufactured to a high and consistent quality. And most importantly, that these products have been proven safe and effective for patients.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Greater Levels of Vitamin D Associated with Decreasing Risk of Breast Cancer

Researchers at University of California San Diego School of Medicine suggest higher levels of vitamin D are associated with decreasing risk of breast cancer. Their epidemiological study is published in the June 15 online issue of PLOS ONE , in collaboration with Creighton University, Medical University of South Carolina and GrassrootsHealth, an Encinitas-based nonprofit organization that promotes vitamin D research and its therapeutic benefits.

The scientists pooled data from two randomized clinical trials with 3,325 combined participants and a prospective study involving 1,713 participants to examine the association between risk of female breast cancer and a broad range of serum 25-hydroxyvitamin D (25(OH)D) concentrations, which was chosen as the marker because it is the main form of vitamin D in blood.

All women were age 55 or older. The average age was 63. Data were collected between 2002 and 2017. Participants were free of cancer at enrollment and were followed for a mean period of four years. Vitamin D levels in blood were measured during study visits.

Over the course of the combined studies, 77 new cases of breast cancer were diagnosed for an age-adjusted incidence rate of 512 cases per 100,000 person-years.

Researchers identified the minimum healthy level of 25(OH)D in blood plasma to be 60 nanograms per milliliter, substantially higher than the 20 ng/ml recommended in 2010 by the Institute of Medicine, now the National Academy of Medicine, a health advisory group to the federal government. Some groups, such as GrassrootsHealth, have advocated higher minimums for health blood serum levels of vitamin D, as much as 50 ng/ml. The matter remains hotly debated.

"We found that participants with blood levels of 25(OH)D that were above 60 ng/ml had one-fifth the risk of breast cancer compared to those with less than 20 ng/ml," said principal investigator and co-author Cedric F. Garland, DrPH, adjunct professor in the UC San Diego Department of Family Medicine and Public Health. Risk of cancer appeared to decline with greater levels of serum vitamin D. 

Multivariate regression was used to quantify the association between 25(OH)D and breast cancer risk, with the results adjusted for age, body mass index, cigarette smoking and intake of calcium supplements, said first author Sharon McDonnell, an epidemiologist and biostatistician for GrassrootsHealth. "Increasing vitamin D blood levels substantially above 20 ng/ml appears to be important for the prevention of breast cancer.”

Garland, who has previously studied connections between serum vitamin D levels and several types of cancer, said the study builds upon previous epidemiological research linking vitamin D deficiency to a higher risk of breast cancer. Epidemiological studies analyze the distribution and determinants of health and disease, but it has been argued that they do not necessarily prove cause-and-effect. 

"This study was limited to postmenopausal breast cancer. Further research is needed on whether high 25(OH)D levels might prevent premenopausal breast cancer," Garland said. The population was also mainly white women so further research is needed on other ethnic groups.

“Nonetheless, this paper reports the strongest association yet between serum vitamin D and reduction in risk of breast cancer,” Garland said.

Garland and others have advocated the health benefits of vitamin D for many years. In 1980, he and his late brother Frank C. Garland, also an epidemiologist, published an influential paper that posited vitamin D (produced by the body through exposure to sunshine) and calcium (which vitamin D helps the body absorb) together reduced the risk of colon cancer. The Garlands and colleagues subsequently found favorable associations of markers of vitamin D with breast, lung and bladder cancers, multiple myeloma and adult leukemia.

To reach 25(OH)D levels of 60 ng/ml, said Garland, would generally require dietary supplements of 4,000 to 6,000 international units (IU) per day, less with the addition of moderate daily sun exposure wearing very minimal clothing (approximately 10-15 minutes per day outdoors at noon).  He said the success of oral supplementation should be determined using a blood test, preferably during winter months.

The current recommended average daily amount of vitamin D3 is 400 IU for children up to one year; 600 IU for ages one to 70 years (including pregnant or breastfeeding women) and 800 IU for persons over age 70, according to the National Academy of Medicine. 

A 2009 paper published in the Annals of Epidemiology by Garland and colleagues recommended a healthy target level of serum 25(OH)D of 40 to 60 ng/ml, based on an expert consensus panel. This statement was published in Annals of Epidemiology (2009). Oral doses of vitamin D are often not specified since different individuals require different intakes to achieve targeted serum range. Except under medical supervision and monitoring, intake of vitamin D3 must not exceed 10,000 IU per day. Blood serum levels exceeding 125 ng/ml have been linked to adverse side effects, such as nausea, constipation, weight loss, heart rhythm problems and kidney damage.

Co-authors include: Edward D. Gorham, UC San Diego; Carole A. Baggerly, Christine B. French and Leo Baggerly, GrassrootsHealth; Bruce W. Hollis of the Medical University of South Carolina; Donald L. Trump, Inova Schar Cancer Center, Falls Church, Va.; and Joan M. Lappe, Creighton University.

Funding for this research came, in part, from the National Institute on Aging (AG14683), the National Cancer Institute (CA129488) and GlaxoSmithKline.

Kids’ Fracture Risk & K2 deficiency Linked in Recent Study

A new pilot study¹ evaluating vitamin D and K status in children with and without low-energy fractures has published in Nutrients, an international, peer-reviewed journal for studies related to Human Nutrition. 

The publication of this study, “Decreased Levels of Circulating Carboxylated Osteocalcin in Children with Low Energy Fractures: A Pilot Study,” is significant because it adds to the growing body of evidence that Vitamin K2 is a beneficial nutrient for both children and adults, according to NattoPharma Chief Medical Officer Dr. Hogne Vik.

“This trial reaffirms the real health benefits improving K2 status delivers,” says Vik. “More importantly, it shines a light on the true impact improving K2 status has on children, our most precious resource.”

According to Dr. Vladimir Badmaev, author of the paper and principal and founder of American Medical Holdings, Inc., “The epidemiological evidence indicates a disturbing growth in the number of cases of low-energy fractures in healthy children and adolescents. There are multiple risk factors that may contribute to this growing health concern, and among the leading consideration are deficient or insufficient nutrition and nutrients, including calcium, vitamin D and vitamin K.”

Dr. Badmaev explains that the particular role of vitamin K2, especially menaquinone-7 (MK-7), has been highlighted in the literature and distinguished from vitamin K1 in maintaining calcium homeostasis and healthy skeletal system. “The epidemiological and clinical research provides a new nutritional paradigm for efficient, safe delivery of calcium that requires co-supplementation with both vitamins D and K.”

The gravitas for this study, which was recently presented at The World Congress on Osteoprosis, Osteoarthritis, and Musculoskeletal Diseases, the world’s leading clinical conference on bone, joint, and muscle health, is increased by Nutrients, a leading European journal with a high impact factor (a measure of how often it is cited by other researchers), selecting it for publication.

“It cannot be overstated the importance of every possible opportunity to advance industry and academic understanding of this essential nutrient,” Vik concludes. “The findings are so very significant, as they provide supporting evidence to the clinical research NattoPharma has already spearheaded. Not only has our research identified children as a group most deficient in Vitamin K2, but that just 45mcg of K2 (as NattoPharma’s MenaQ7®) daily improves K status and increases the activation of osteocalcin, the K-dependent protein responsible for binding calcium to the bone mineral matrix, therefore improving bone health.”

Reference:

Popko J, Karpinski M, Chojnowska S, Maresz K, Milewski R, Badmaev V, Schurgers L. Decreased Levels of Circulating Carboxylated Osteocalcin in Children with Low Energy Fractures: A Pilot Study. Nutrients 2018, 10(6), 734. https://doi.org/10.3390/nu10060734

Children's Fluoride Exposures Linked to Later Life Disease?

"[F]luoride exposures in early life could influence or originate the root-cause of certain diseases in later life," write researchers in The Journal of Clinical Pediatric Dentistry (5/2018), reports the New York State Coalition Opposed to Fluoridation, Inc. (NYSCOF)

Nakamoto and Rawls, from the Health Sciences Centers of Louisiana State University and the University of Texas, respectively, write, "When fluoride was discovered to prevent dental caries, it was hailed as one of the greatest discoveries of the 20th century. Since then, there have been numerous reports that fluoride may possibly be associated with health-related problems," such as Autism, lowering IQ, bone diseases, thyroid, and sleep disorders, they explain.

"The greatest fluoride accumulation occurs in the hippocampus portion of the brain," they write.

"For children and young adults, early-life exposure to fluoride could become the root of the development of neurodegenerative disease [e.g. autism] in later life," they write.

Fluoride is a developmental neurotoxicant linked to lower IQ, they explain.

Attorney Paul Beeber, NYSCOF President says, "As a precaution, it's important for pregnant women to be told they should limit their fluoride intake."

Besides water fluoridation, fluoride is in a variety of foods and dental products, in varying and mostly unknown quantities, which has created a new problem – dental fluorosis – white-spotted, yellow, brown and/or pitted teeth afflicting 57% of 6-19-year-olds.

The researchers suggest children with fluorosis be checked for thyroid disorders.

They explain that excessive fluoride intake by the young could result in nutritional stresses during critical growth period. "Some of the body's 'memories' of early fluoride exposure may become translated into pathology and thereby determine disease in later life," they write.

They lament that it's unfortunate fluorosis is treated as a cosmetic effect and that there isn't more concern about the consequences of fluoride exposures to the children's general health. 

"If the root of adult disease is already seeded by the exposures of fluoride during this period, one can even argue that fetal, newborn and childhood nutritional environment is as important as adult dietary habit and lifestyle," they write.

Beeber says, "Most fluoride research and promotion is based on dental effects. Governments must stop ignoring the science showing fluoride's adverse health effects to other body systems and organs and stop fluoridation."

Life Extension® clinical study finds KaempMax™, a Kaempferia parviflora ethanol extract, enhances male sexual health

Erectile dysfunction is a pervasive problem and can considerably undermine men's quality of life and psychological health. Drugs such as Viagra and other phosphodiesterase 5 (PDE5) inhibitors are currently the first line of therapy for erectile dysfunction, but they don't work for all men, and cause adverse effects in some.  

In a pilot study published online in June 2018 in the Journal of Integrative Medicine, scientists from Life Extension, an industry leader in dietary supplement innovation, reported that KaempMax™, an ethanolic extract of K. parviflora rhizome, improved self-assessed sexual health in middle-aged and older men who reported having mild erectile dysfunction.1

"Results from our study together with those previously published suggest that K. parviflora extract may benefit male sexual health and provides an option for those seeking nonprescription alternatives," said Andrew Swick, PhD, senior vice president of product development and scientific affairs for Fort Lauderdale, Fla.-based Life Extension and an author of the new study.

Erectile dysfunction is increasingly recognized as an early manifestation of cardiovascular disease and may precede the development of overt heart problems such as heart attacks, sometimes by several years. Endothelial dysfunction is at the center of the shared pathology between the two conditions, and preserving endothelial function is essential for cardiovascular and erectile health. K. parviflora has been used traditionally to support cardiovascular and male sexual health, and contemporary studies have shown that K. parviflora extract supports endothelial function.3,4

Thirteen generally healthy men aged 50 to 68 years completed the 30-day clinical trial. Participants took 100 mg of KaempMax™ daily. The International Index of Erectile Function (IIEF) and the Global Assessment Question (GAQ) about erectile function were used to assess the efficacy of the treatment.

Supplementation with KaempMax™ led to a statistically significant improvement in erectile function, intercourse satisfaction, and total scores on the IIEF questionnaire. Most participants found the study product satisfactory and no serious adverse effects were reported.

These findings build on those from a small 2012 study conducted in Thailand that found K. parviflora rhizome extract improved erectile response in older men.2 "Both the Thai study and our pilot study found no changes in testosterone levels with K. parviflora treatment, suggesting that it mediates its effects via non-hormonal mechanisms," said Dr. Steven Hirsh, Director of Clinical Research at Life Extension and a study author.

"This exciting new pilot study lends support to traditional Asian medicinal uses of K. parviflora for male sexual function," says Richard A. Stein, MD, PhD, the study's lead author. "We are hopeful that these findings will spur larger trials exploring the potential of K. parviflora extracts to enhance men's sex lives."