Pygeum: Plant-Based Extract for Prostate Health

Prunus africana, or African plum, was formerly classified as Pygeum africanum— a name under which it is still often known. In the Western world, an extract of Prunus africana bark is most popularly used for benign prostate hyperplasia (BPH, or prostate enlargement). Traditional uses include treatment of fever, malaria, wounds, stomach upset, kidney disease, and more.

History of Pygeum

Pygeum africanum, a member of the Rosaceae family, is an evergreen species found across the entire continent of Africa at altitudes of 3,000 feet or higher,” reports Alternative Medicine Review. “Interest in the species began in the 1700s when European travelers learned from South African tribes how to soothe bladder discomfort and treat ‘old man’s disease’ with the bark of P. africanumPygeum is … [a] commonly used medicine in France for BPH, backed by many double-blind studies pointing to its efficacy for reducing its symptoms.”1

Early scientific research documented a benefit for Prunus africana in combination with a locally acting nonsteroidal anti-inflammatory drug known as benzidamine among patients suffering from prostate disorders.2 The researchers noted that good results were achieved in 90% of the cases and that there was no toxicity. Another early human study found improvements in nighttime urinary frequency, difficulty in starting urination, and incomplete emptying of the bladder in men given Pygeum extract.3

Clinical Trials with Pygeum

In 1990, the results of a multicenter, double-blind trial were published. This study included men with BPH and found improvements in urine flow, residual urine, and urination frequency at more than twice the rate in participants who received Pygeum extract for 60 days compared to a placebo group.4 The following year, a paper was published detailing the results of a trial that investigated Pygeum’s effects among men with either BPH or chronic inflammation of the prostate. In this study, Pygeum administration improved all urinary parameters investigated, including periurethral swelling.5 Another trial found an improvement in symptoms of BPH with a combination of Pygeum and Urtica dioica (nettle) root extract after 28 and 56 days.6

A multicenter trial reported in 1998 that included 85 men from the ages of 50 to 75 who received Pygeum for two months found a 40% improvement in International Prostate Symptom Scores and a 31% increase in quality of life after two months.7 Nighttime urination decreased by 32%, and improvements were observed in average maximum urinary flow, average urinary flow, and urinary volume. The changes exceeded those observed in association with a placebo in earlier studies and were still evident at an evaluation one month after the treatment was discontinued.

A meta-analysis published in December 2000 that included 18 randomized, controlled trials involving a total of 1,562 men found that subjects treated with Pygeum were more than twice as likely to report an improvement in overall symptoms than the control subjects. The investigators concluded that P. africanum significantly improves urologic symptoms and flow measures.8

Mechanisms of Action: How it Works

Pygeum, like saw palmetto, contains beta-sitosterol, which inhibits the enzyme 5 alpha-reductase that facilitates the conversion of testosterone to dihydrotestosterone (DHT), the hormone that is the cause of BPH.1,9-11 In research involving rats treated with DHT, pretreatment with Pygeum extract decreased the obstructive effects of DHT on urination and counteracted DHT-induced prostate enlargement.12 Pygeum has also shown an inhibitory effect against aromatase, an enzyme involved in the synthesis of estrogens, including the transformation of testosterone to estradiol.13

In rat prostate cells, Pygeum was shown to inhibit proliferation resulting from various growth factors. The researchers concluded that “Pygeum africanum is a potent inhibitor of rat prostatic fibroblast proliferation in response to direct activators of protein kinase C, the defined growth factors bFGF, EGF, and IGF-I, and the complex mixture of mitogens in serum depending on the concentration used. Protein kinase C activation appears to be an important growth factor¬¬–¬mediated signal transduction for this agent. These data suggest the therapeutic effect of Pygeum africanum may be due at least in part to the inhibition of growth factors responsible for the prostatic overgrowth in man.”14

Potential Anticancer Effects

In a paper published in 2007, researchers at the University of Missouri observed that extracts of Pygeum inhibited growth in two different prostate cancer cell lines, while inducing apoptosis (programmed cell death) and other changes. In the results from a mouse model of prostate cancer that was published in this same paper, animals that were fed Pygeum had a greater than 27% lower incidence of prostate cancer than a control group given casein.15

A review of Pygeum bark compounds identified ursolic acid, oleanolic acid, atraric acid, ferulic acid, N-butylbenzene-sulfonamide (NBBS), beta-sitosterol, and lauric acid as having the potential to aid in the prevention and treatment of prostate cancer. “Through synergistic interactions between different effective phytochemicals, P. Africana extracts have been shown to exhibit very strong antiandrogenic and antiangiogenic activities and have the ability to kill tumor cells via apoptotic pathways, prevent the proliferation of prostate cancer cells, and alter the signaling pathways required for the maintenance of prostate cancer cells,” write authors Richard Komakech and colleagues.16

Although Pygeum’s potential effects in prostate cancer appear worthy of investigation, it is recommended that men diagnosed with the disease follow the treatment regimen recommended by their physicians.

The Bottom Line

For men whose prostate enlargement is benign and not severe, Pygeum extract may be worth a trial. It takes a few months for symptoms to improve, so don’t give up too soon!

A double-blind trial that compared the effects of 50 milligrams of Pygeum twice per day and 100 milligrams once daily found that both treatments were associated with similar improvements in International Prostate Symptom Score, quality of life, and maximum urinary flow rate.17

References

  1. No authors listed. Altern Med Rev. 2002 ;7(1):71-4.
  2. Ahmad Samhan K et al. Arch Esp Urol. 1980 Jul-Aug;33(4):417-24.
  3. Dufour B et al. Ann Urol (Paris). 1984 May;18(3):193-5.
  4. Barlet A et al. Wien Klin Wochenschr. 1990 Nov 23;102(22):667-73.
  5. Carani C et al. Arch Ital Urol Nefrol Androl. 1991 Sep;63(3):341-5.
  6. Krzeski T et al. Clin Ther. 1993 Nov-Dec;15(6):1011-20.
  7. Breza J et al. Curr Med Res Opin. 1998;14(3):127-39.
  8. Ishani A et al. Am J Med. 2000 Dec 1;109(8):654-64.
  9. No authors listed. Proc West Pharmacol Soc. 2003;46:153-5.
  10. No authors listed. Altern Med Rev. 1998 3(3):227-229
  11. No authors listed. 2018 Jan;5(1):28-32.
  12. Choo MS et al. Urology. 2000 Feb;55(2):292-8.
  13. Hartmann RW et al. Phytomedicine. 1996 Sep;3(2):121-8.
  14. Yablonsky F et al. J Urol. 1997 Jun;157(6):2381-7.
  15. Shenouda NS et al. Endocrine. 2007 Feb;31(1):72-81.
  16. Komakech R et al. Evid Based Complement Alternat Med. 2017;2017:3014019.
  17. Chatelain C et al. Urology. 1999 Sep;54(3):473-8.

Not Your Mother's Rhubarb: Menopause Relief with Plant-Based, Hormone-Free Supplement

By Holli Ryan RD, LD/N and Life Extension Staff


Menopause is a certainty for women. But suffering from unpleasant menopausal symptoms doesn’t have to be. Thanks to a special extract of the Siberian rhubarb plant, menopausal discomfort has met its match.





You’re probably thinking … wait, what is Siberian rhubarb? That is, unless you’re from Germany. That’s because it’s still relatively unknown in the United States but has been used successfully to manage the symptoms of menopause in Germany since 1993. However, it is starting to gain momentum in the U.S. thanks to the stellar results from clinical research studies.

The unique extract from Siberian rhubarb root (botanically named Rheum rhaponticum L.) is a clinically effective and convenient, plant-based compound that relieves menopause-related discomforts, and perimenopausal and postmenopausal women are taking note.

menopause supplement Siberian rhubarb Rheum rhaponticum L. plant
Siberian rhubarb plant


What Are the Symptoms of Menopause?

In the most recent season of the popular prison-based Netflix show Orange Is the New Black (spoiler alert!), one of the inmates recognized menopause as having the same symptoms as being incarcerated.

Menopause is characterized by symptoms such as hot flashes, night sweats, mood swings, sleep disturbances, vaginal dryness, and more. A standardized assessment tool that researchers and doctors use, called the Menopause Rating Scale, identifies 11 separate symptoms of menopause.1

Siberian rhubarb extract has been shown to reduce all 11 menopause symptoms by as much as 83% in human studies!2

What about Hormone Restoration?

A sharp drop in estrogen levels contributes to menopausal symptoms. One option for women seeking to alleviate those symptoms is to use prescription hormone replacement therapy, including estrogen, to restore youthful hormone levels.

There are two hormone replacement approaches. Conventional Hormone Restoration Therapy (HRT) and Bioidentical Hormone Restoration Therapy (BHRT). Life Extension® has long advocated for the benefits of BHRT over conventional methods.

While BHRT is generally safe and effective, Siberian rhubarb extract may be an appealing alternative for women seeking menopause support without the use of hormones. Especially an alternative that, once again, provides relief for all 11 symptoms on the Menopause Rating Scale! Results like that are worth saying twice. So if you’re looking for the best over-the-counter option for menopause relief, consider it found.

Siberian rhubarb extract reduced the number and severity of hot flashes to a similar extent as expected with conventional hormone replacement therapy, though no direct comparison studies have been conducted.3 Studies also showed that Siberian rhubarb improved depressive mood-related symptoms.2,4,5

Mechanism of Action: How Does it Work?

Two compounds found in Siberian rhubarb called rhaponticin and desoxyrhaponticin are responsible for the beneficial effects.

These rhubarb compounds bind primarily to estrogen receptor beta (ER–beta).6 Activation of ER–beta confers favorable health effects in some tissues under some circumstances.7

The Science

Clinical studies, together examining more than 400 peri- and postmenopausal women, evaluated the effects of a 4 mg daily dose of Siberian rhubarb extract.2-5 The studies used standardized assessment tools like the Menopause Rating Scale and showed that Siberian rhubarb extract consistently reduced symptom severity by up to 83%.

During the time these studies were being carried out, 6.7 million doses were sold in Germany each year.8

When Can I Expect Results?

Safe and effective? Yes. Will it work instantly? No. As is the case with many herbal supplements, it will take some time for the potential benefits to become apparent. In one study, some effects were seen as early as four weeks, with the best effects seen after 12 weeks. 3 At week 12, the treatment group experienced a 54% improvement in the severity of menopause symptoms compared to baseline. Additional studies looked at long-term effects at the six-month mark and over two years and found that benefits continued with use. Life Extension® suggests following the study duration for best results. Feel free to give us a call for more info. Call our Wellness Specialists — at no charge! — at 1-800-226-2370. If you end up purchasing any products during your call, mention code SHIPFREE for free shipping!*

*Offer valid beginning on 9/3/18 for a limited time.

About the author: Holli (Lapes) Ryan RD, LD/N is a Social Media Content Specialist at Life Extension. She is a Registered and Licensed Dietitian Nutritionist residing in the South Florida area. Holli believes that quality dietary supplements are an essential tool that have a variety of applications from maintaining good health to managing chronic disease. 







References:

  1. Heinemann K, Ruebig A, Potthoff P, et al. The Menopause Rating Scale (MRS) scale: A methodological review. Health Qual Life Outcomes. 2004;2:45-45.
  2. Hasper I, Ventskovskiy BM, Rettenberger R, Heger PW, Riley DS, Kaszkin-Bettag M. Long-term efficacy and safety of the special extract ERr 731 of Rheum rhaponticum in perimenopausal women with menopausal symptoms. Menopause. Jan-Feb 2009;16(1):117-131.
  3. Heger M, Ventskovskiy BM, Borzenko I, et al. Efficacy and safety of a special extract of Rheum rhaponticum (ERr 731) in perimenopausal women with climacteric complaints: a 12-week randomized, double-blind, placebo-controlled trial. Menopause. Sep-Oct 2006;13(5):744-759.
  4. Kaszkin-Bettag M, Beck S, Richardson A, Heger PW, Beer AM. Efficacy of the special extract ERr 731 from rhapontic rhubarb for menopausal complaints: a 6-month open observational study. Altern Ther Health Med. Nov-Dec 2008;14(6):32-38.
  5. Kaszkin-Bettag M, Ventskovskiy BM, Solskyy S, et al. Confirmation of the efficacy of ERr 731 in perimenopausal women with menopausal symptoms. Altern Ther Health Med. Jan-Feb 2009;15(1):24-34.
  6. Wober J, Moller F, Richter T, et al. Activation of estrogen receptor-beta by a special extract of Rheum rhaponticum (ERr 731), its aglycones and structurally related compounds. J Steroid Biochem Mol Biol. Nov-Dec 2007;107(3-5):191-201.
  7. Paterni I, Granchi C, Katzenellenbogen JA, Minutolo F. Estrogen Receptors Alpha (ERα) and Beta (ERβ): Subtype-Selective Ligands and Clinical Potential. Steroids. Nov 2014;90:13-29.
  8. Chang JL, Montalto MB, Heger PW, Thiemann E, Rettenberger R, Wacker J. Rheum rhaponticum Extract (ERr 731): Postmarketing Data on Safety Surveillance and Consumer Complaints. Integr Med (Encinitas). Jun 2016;15(3):34-39.


Kombucha: Got Culture? Potential Health Benefits of Trendy Drink

They’re popping up in trendy neighborhoods. And while they may be a sign that a neighborhood has culture, we’re not talking about museums and art galleries. We’re talking about bars that serve something different on tap!

Instead of pouring alcoholic beverages, these bars are serving up varieties of kombucha, a fermented beverage that does actually contain a small amount of alcohol but, more important, is purported to grant a number of health benefits.

Related Article: The Importance of Fermented Foods

Health Fad or Real Benefits?

While erroneously believed by some people to be a type of mushroom, kombucha is actually black or green tea fermented with a culture of bacteria and yeast. It is a source of probiotics, which are beneficial bacteria. The beverage originated in Manchuria over 2,000 years ago and was later exported to Japan. It has been popular in Russia and Germany and began appearing in the U.S. two decades ago. The mildly effervescent beverage is frequently consumed sweetened, but its acidic taste is savored by aficionados.

“Although the beneficial and/or adverse effects of kombucha tea on human health have not been scientifically determined yet, there are several reasons to believe that kombucha may have desirable positive effects on human health,” note Ahmed Aloulou and colleagues in BMC Complementary and Alternative Medicine. The authors point out that several recent studies demonstrate that kombucha can reduce cell damage caused by oxidative stress. They further note that kombucha is reported to improve resistance against cancer, prevent cardiovascular diseases, promote healthy digestion, stimulate the immune system, and reduce problems related to inflammation.1

Kombucha’s main biological functions have been identified as glucuronic acid production, antibacterial activity, and antioxidant activity.2


Antioxidant-related Effects

In rats that received a lead acetate solution daily (which induces oxidative stress), kombucha lowered lipid peroxidation and DNA damage while increasing the levels of reduced glutathione and glutathione peroxidase, the latter being one of the body’s antioxidant enzymes.3 It also alleviated lead-induced immunosuppression.

In another rat study, oral administration of kombucha offered protection against the effects of stress induced by exposure to cold and low oxygen conditions, indicated by the prevention of a decline in reduced glutathione and lipid peroxidation, and helped protect the liver against acetaminophen-induced toxicity.4

In a mouse model of stomach ulceration induced by the drug indomethacin, kombucha demonstrated the best healing effects in comparison with black tea or tea fermented with Candida parapsilosis. Kombucha’s superior effects were attributed to its antioxidant activity and its protective effect on gastric mucin content.5 The authors note that the kombucha tea used in this study was as effective at healing ulcers as the proton pump inhibitor omeprazole.

Cardiometabolic Effects

In rats in which diabetes was induced by administration of the compound alloxan, kombucha extract given for 14 days was more effective than unfermented black tea at reversing some of the adverse changes induced by alloxan, including those observed in pancreatic tissue.6 Another study involving alloxan-treated diabetic rats given kombucha or an unfermented tea found that kombucha was better than black tea at suppressing elevated blood glucose. It was discovered that kombucha lowered the activity of alpha-amylase, a pancreatic enzyme that plays a role in the digestion of carbohydrates, and pancreatic lipase, which breaks down dietary fats. Kombucha was also associated with an increase in high-density lipoprotein (HDL) cholesterol, protection of kidney and liver function, and other positive effects, leading the researchers to conclude that kombucha tea can be considered a strong candidate as a potential functional supplement to treat and prevent diabetes.1

A study of rats that underwent myocardial infarction subsequent to injection of the drug isoproterenol revealed a protective effect for pretreatment with kombucha against increases in heart weight, blood glucose, and albumin, accompanied by decreases in total, low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL) cholesterol; triglycerides; and leakage of cardiac markers from the heart muscle.7

Among rats fed high cholesterol diets that received kombucha or green tea for 16 weeks, kombucha more effectively raised HDL cholesterol and lowered triglycerides and serum total, LDL, and VLDL cholesterol.8 Kombucha was also associated with a lower marker of lipid peroxidation in the liver and kidney compared to animals that received a high cholesterol diet alone. The authors suggest that kombucha tea be evaluated in humans.

Related Article: The Most Important Blood Tests Available for Assessing Cardiovascular Risk


Miscellaneous Effects

In mice, three years of consuming kombucha was associated with greater exploration and object manipulation, as well as longer life, in comparison with animals that were not given the beverage.9

An ethyl acetate fraction of kombucha tea injected into the skin of aged mice significantly increased collagen and NAD+/NADH levels.10 Kombucha improved connective tissue abnormalities associated with aging without inducing sensitivity or irritation.

One study found a protective effect for kombucha tea against carbon tetrachloride–induced liver toxicity that was greater than that of black tea.11 Subsequent research identified a compound produced by a specific bacterial strain in kombucha that may be responsible for its liver-protective effect.12

Research has also revealed the presence of isorhamnetin, an antibacterial flavonoid in kombucha that is not present in unfermented tea.13 The study is the first to identify the flavonoid in kombucha and concludes that kombucha can be used against enteropathogenic bacterial infections due to its polyphenolic content.

Safety Profile

A concern has been raised regarding the safety of the beverage, which is often fermented by home cultivators for a week or more at room temperature. An examination of kombucha for contamination led researchers at Germany’s Justus Liebig University to the conclusion that kombucha is safe; however, it is suggested that immunosuppressed individuals consume commercial kombucha beverages whose production is regulated.14 Kombucha has been shown to have an antibacterial effect against Staphylococcus aureus, Shigella sonnei, Escherichia coli, Aeromonas hydrophila, Yersinia enterocolitica, Pseudomonas aeruginosa, Enterobacter cloacae, Staphylococcus epidermidis, Campylobacter jejuni, Salmonella typhimurium, Salmonella enterica serotypeEnteritidis, Bacillus cereus, Helicobacter pylori, and Listeria monocytogenes.15 Studies in rats given kombucha tea for 90 days found no toxic effects.16

“The recent experimental studies on the consumption of kombucha tea suggest that it is suitable for prevention against broad-spectrum metabolic and infective disorders,” Ilmāra Vīna and colleagues conclude in a 2014 review17. “This makes kombucha tea attractive as a fermented functional beverage for health prophylaxis.”

The Bottom Line

While more human studies are needed to substantiate the benefits of kombucha, its rich supply of probiotics may be the top reason to drink it. Research has shown the species Lactobacillus is prominent.18 Interestingly, NASA is researching the efficacy of probiotics in foods for astronauts, and kombucha may be a viable option. International researchers state that “the astronaut’s diet is not rich enough in vegetables (soluble and insoluble fibers), and taking probiotics may not be so effective” because of insufficient food sources for the probiotic bacteria. Since probiotic bacteria require prebiotics as a food source for the bacteria to thrive, “kombucha tea … may be a promising formulation of a probiotic/prebiotic for extreme expeditions.” The authors also highlight that kombucha provides a source of both probiotic bacteria and yeast, as well as prebiotics (microcellulose), which help fuel the growth of helpful microorganisms in the gut.19

References

  1. Aloulou A et al. BMC Complement Altern Med. 2012 May 16;12:63.
  2. Nguygen NK et al. Springerplus. 2015 Feb 24;4:91.
  3. Dipti P et al. Biomed Environ Sci. 2003 Sep;16(3):276-82.
  4. Pauline T et al. Biomed Environ Sci. 2001 Sep;14(3):207-13.
  5. Banerjee D et al. Food Funct. 2010 Dec;1(3):284-93.
  6. Bhattacharya S et al. Food Chem Toxicol. 2013 Oct;60:328-40.
  7. Lobo RO et al. J Food Sci Technol. 2015 Jul;52(7):4491-8.
  8. Bellassoued K et al. Pharm Biol. 2015;53(11):1699-709.
  9. Hartmann AM et al. Nutrition. 2000 Sep;16(9):755-61.
  10. Pakravan N et al. J Cosmet Dermatol. 2017 Nov 19.
  11. Murugesan GS et al. J Microbiol Biotechnol. 2009 Apr;19(4):397-402.
  12. Wang Y et al. J Sci Food Agric. 2014 Jan 30;94(2):265-72.
  13. Bhattacharya D et al. Curr Microbiol. 2016 Dec;73(6):885-896.
  14. Mayser P et al. Mycoses. 1995 Jul-Aug;38(7-8):289-95.
  15. Sreeramulu G et al. J Agric Food Chem. 2000 Jun;48(6):2589-94.
  16. Vijayaraghavan R et al. Biomed Environ Sci. 2000 Dec;13(4):293-9.
  17. Vīna I et al. J Med Food. 2014 Feb;17(2):179-88.
  18. Marsh AJ et al. Food Microbiol. 2014 Apr;38:171-8.
  19. Kozyrovska et al. Biopolymers and Cell. 2012 January; 28(2):103-113.

The Health Benefits of Honokiol from Magnolia Plant

The plant genus Magnolia includes over 200 species of flowering plants that grow in Asia and the Americas. Magnolias have been around since the time of dinosaurs — before bees existed! — and are thus pollinated by beetles. In the American South, the trees are treasured for their fragrant blooms. But other aspects of magnolias appear to be even greater treasures.

“Magnolia officinalis and Magnolia obovata bark extracts have been used for thousands of years in Chinese and Japanese traditional medicines and are still widely employed as herbal preparations for their sedative, antioxidant, anti-inflammatory, antibiotic, and antispastic effects,” write A. Sarrica and colleagues in a review article. As the review points out, neolignans, and in particular magnolol and honokiol, are the main substances that explain the beneficial properties of the magnolia bark extract.1

Honokiol and magnolol were reported in 1975 to have a long-lasting muscle-relaxing effect in mice.2 This relaxing effect may be due to the compounds’ interaction with receptors for gamma aminobutyric acid (GABA), a key neurotransmitter.3 A randomized, placebo-controlled trial involving overweight, premenopausal women resulted in a reduction in mild transitory anxiety in those who received an extract of magnolia combined with the herb Phellodendron amurense.4

Cancer Research

One of the most-promising areas of research involving honokiol is against cancer. “Investigations have demonstrated that honokiol possesses anticarcinogenic, anti-inflammatory, anti-oxidative, anti-angiogenic as well as inhibitory effect on malignant transformation of papillomas to carcinomas in vitro and in vivo animal models without any appreciable toxicity,” write R. Prasad and S. K. Katiyar in Advances in Experimental Medicine and Biology. The authors mention that honokiol affects multiple signaling pathways and that some of its molecular and cellular targets include nuclear factor-κB, STAT3, epidermal growth factor receptor, cell-survival-signaling pathways, the cell-division cycle, and cyclooxygenase. Additionally, its chemopreventive and therapeutic effects have been tested against chronic diseases, including various cancers.5

An extract of Magnolia officinalis as well as magnolol have shown inhibitory effects against skin carcinogenesis in mice.6 In human fibrosarcoma cells, magnolol and honokiol inhibited tumor invasiveness.7 In mice with colorectal cancer, honokiol inhibited tumor growth and prolonged life.8 In human colorectal carcinoma cells, honokiol inhibited cellular growth by inducing apoptosis (programmed cell death).9 The compound also has been shown to induce apoptosis in gastric cancer cells, in addition to decreasing tumor growth in mice that received transplanted gastric cancer cells.10 In a study that tested honokiol’s effects in B-cell chronic lymphocytic leukemia, honokiol induced apoptosis and enhanced the cytotoxicity of chemotherapy.11 In multiple myeloma cells, honokiol induced apoptosis in addition to enhancing apoptosis induced by the drug bortezomib.12 Honokiol has also induced apoptosis in prostate cancer cells and inhibited the growth of bone metastases in mice.13 Other research involving human breast cancer cells found induction of apoptosis and cell-cycle inhibition associated with exposure to honokiol.14

Honokiol has shown inhibitory effects against angiogenesis, the formation of new blood vessels that facilitate tumor growth.15 In human breast cancer cells, honokiol downregulated P-glycoprotein, whose expression is responsible for acquired cancer multidrug resistance.16 Honokiol and magnolol have also shown cytotoxic activity against human ovarian adenocarcinoma, hepatocellular carcinoma, and cancer of the cervix.17 These and many other studies suggest a potential role for the compounds in cancer prevention and treatment in humans.

Antimicrobial Effects

In addition to their activity against cancer cells, honokiol and magnolol are active against a variety of undesirable microbes. Although less potent than chlorhexidine, honokiol and magnolol have shown activity against several periodontal microorganisms while demonstrating little toxicity in human gingival cells. The researchers involved in the study suggest that magnolol and honokiol may have a potential use as a safe oral antiseptic for preventing and treating periodontal disease.18 This activity may be responsible for magnolia bark’s ability to block bacteria responsible for oral malodor, which was demonstrated in a human study.19 Another trial that investigated magnolia’s oral effects showed a reduction in gingival inflammation in association with the use of a dentifrice that contained magnolia extract as compared to a control dentifrice.20 Honokiol and magnolol also have shown activity against several species of fungi, including Candida albicans (responsible for oral “thrush”) and an antiviral effect against HIV-1 and hepatitis C.21-23

Inflammation

Honokiol and magnolol have antioxidant as well as anti-inflammatory effects.24 A recent study that evaluated the effects of magnolol and honokiol in the intestinal epithelium of mice with diarrhea resulting from E. coli bacteria found that the compounds enhanced intestinal anti-inflammatory capacities, inhibited intestinal epithelium apoptosis, and protected intestinal mucosa.25 In an asthmatic mouse model, honokiol inhibited eosinophil infiltration, decreased airway inflammation, and suppressed inflammatory cytokine production, prompting the authors of the study to recommend its possible use for yet another human disease.26

Anti-Aging Effects

Honokiol has been identified by researchers as an inhibitor of aromatase, an enzyme that converts testosterone to estradiol.27 Theyalso found that honokiol inhibited 5-alpha-reductase-1, one of two enzymes that converts testosterone to dihydrotestosterone, a hormone that can contribute to male pattern hair loss. By reducing the activity of these enzymes, honokiol could help preserve healthy testosterone levels in men.

Honokiol can also benefit the brain. It can permeate the blood-brain barrier and the blood–cerebrospinal fluid barrier, thus increasing its bioavailability in brain tissue. “Various studies have reported the neuroprotective effects of honokiol in the central nervous system, which are due to its powerful antioxidant activity and its ability to ameliorate excitotoxicity, mainly related to the blockade of glutamate receptors and reduction in neuroinflammation. Other recent studies suggest that honokiol could attenuate neurotoxicity caused by abnormally aggregated amyloid beta in Alzheimer's disease.28

In a mouse model of Alzheimer’s disease, honokiol given for six weeks decreased the production of amyloid beta (which forms the brain plaques that are characteristic of Alzheimer’s disease), reduced plaque deposition, reduced proinflammatory cytokine production, and improved spatial memory defects, all of which indicates that honokiol could be a promising treatment agent for the disease.29 Other research has found that honokiol promotes a transcription factor known as Nrf2, which suggests that honokiol could be developed as a treatment for oxidative stress–related neurodegenerative disorders.30

The Bottom Line

“Magnolia bark extract is a major constituent of currently marketed dietary supplements and cosmetic products,” note M. Poivre and M. Duez in a recent review. As the authors note, some of the important pharmacological activities that have been reported for this herb and its major compounds include antioxidant, anti-inflammatory, antibiotic, and antispasmodic effects.31

It is anticipated that the promising effects reported in preliminary studies of these ancient and beautiful plants will be the subject of further clinical research that will confirm magnolias’ numerous benefits in humans.

References

  1. Sarrica A et al. Planta Med. 2018 Jun 20.
  2. Watanabe K et al. Jpn J Pharmacol. 1975 Oct;25(5):605-7.
  3. Ai J et al. Pharmacology. 2001 Jul;63(1):34-41.
  4. Kalman DS et al. Nutr J. 2008 Apr 21;7:11.
  5. Adv Exp Med Biol. 2016;928:245-265.
  6. Konoshima T et al. J Nat Prod. 1991 May-Jun;54(3):816-22.
  7. Nagase H et al. Planta Med. 2001 Nov;67(8):705-8.
  8. Chen F et al. World J Gastroenterol. 2004 Dec 1;10(23):3459-63.
  9. Wang T et al. World J Gastroenterol. 2004 Aug 1;10(15):2205-8.
  10. Sheu ML et al. PLoS One. 2007 Oct 31;2(10):e1096.
  11. Battle TE et al. Blood. 2005 Jul 15;106(2):690-7.
  12. Ishitsuka K et al. Blood. 2005 Sep 1;106(5):1794-800.
  13. Shigemura K et al. Cancer. 2007 Apr 1;109(7):1279-89.
  14. Wolf I et al. Int J Oncol. 2007 Jun;30(6):1529-37.
  15. Bai X et al. J Biol Chem. 2003 Sep 12;278(37):35501-7.
  16. Xu D et al. Cancer Lett. 2006 Nov 18;243(2):274-80.
  17. Syu WJ et al. Chem Biodivers. 2004 Mar;1(3):530-7.
  18. Chang B et al. Planta Med. 1998 May;64(4):367-9.
  19. Greenberg M et al. J Agric Food Chem. 2007 Nov 14;55(23):9465-9.
  20. Hellström MK et al. Int J Dent Hyg. 2014 May;12(2):96-102.
  21. Amblard F et al. J Med Chem. 2006 Jun 1;49(11):3426-7.
  22. Bang KH et al. Arch Pharm Res. 2000 Feb;23(1):46-9.
  23. Lan KH et al. Liver Int. 2012 Jul;32(6):989-97.
  24. Lee J et al. Planta Med. 2005 Apr;71(4):338-43.
  25. Deng Y et al. Med Sci Monit. 2018 May 21;24:3348-3356.
  26. Hong T et al. Pak J Pharm Sci. 2018 Jul;31(4):1279-1284.
  27. Bernard P et al. Clin Interv Aging. 2012;7:351-61.
  28. Talarek S et al. Biofactors. 2017 Nov;43(6):760-769.
  29. Wang D et al. J Pharmacol Exp Ther. 2018 Jul 10.
  30. Hou Y et al. ACS Chem Neurosci. 2018 Jul 19.
  31. Poivre M et al. J Zhejiang Univ Sci B. 2017 Mar.;18(3):194-214.

Can Creatine Help with Depression?

“I didn’t want to wake up.
I was having a much better time asleep. And that’s really sad.
It was almost like a reverse nightmare, like when you wake up from a nightmare you’re so relieved. I woke up into a nightmare.” –Ned Vizzini, It’s Kind of a Funny Story



Few conditions can be as devastating as depression. The disorder has links with cancer, diabetes, chronic pain, thyroid disorders, multiple sclerosis, and heart disease. Approximately 7% of men and 1% of women with a lifetime history of depression die from suicide.

“The so-called ‘psychotically depressed’ person who tries to kill herself doesn’t do so out of quote ‘hopelessness’ or any abstract conviction that life’s assets and debits do not square. And surely not because death seems suddenly appealing. The person in whom its invisible agony reaches a certain unendurable level will kill herself the same way a trapped person will eventually jump from the window of a burning high-rise.” – David Foster Wallace


Treatment of Depression

While antidepressant drugs have been a lifesaver for many people, they fail to help a significant number of users. In studies of adults, 40 to 60 of 100 people who used an antidepressant noticed improvement within six to eight weeks, compared to 20 to 40 who received a placebo.1

The drugs can also have significant side effects in many people and, in some cases, make the condition worse.

In an effort to obtain relief from what has been termed a “half-life,” depressed individuals may turn to psychotherapy or group therapy. These nondrug therapies can be helpful, although depression is considered to be a biochemical disorder. Nevertheless, it can’t be denied that our thoughts have profound effects on our bodies.

“There is no point treating a depressed person as though she were just feeling sad, saying, ‘There now, hang on, you’ll get over it.’ Sadness is more or less like a head cold— with patience, it passes. Depression is like cancer.” –Barbara Kingsolver, The Bean Trees

Nutritional Solutions: Creatine Research

Good nutrition is the foundation of a sound body and mind. Essential vitamins, minerals, and amino acids all play a role in our mental well-being. Individualized nutritional regimens can be tweaked with the addition of supplements like creatine that have shown promise in preliminary studies. Creatine can also be made in the body from the amino acids arginine, glycine, and methionine.

Creatine plays a vital role in brain energy metabolism,” Tracy L. Hellem, PhD, RN, and colleagues note in a recent article. “Via the creatine kinase reaction, creatine facilitates production of adenosine triphosphate, the nervous system’s principal energy source.”2

A small, preliminary study of creatine monohydrate in eight patients with unipolar depression and two bipolar patients with treatment-resistant depression found significant improvement among the unipolar patients at the end of the four-week study.3

In 2017, the Journal of Clinical Psychopharmacology reported findings from a pilot study that found a benefit for treatment with creatine and 5-hydroxytryptophan (5-HTP, a metabolite of the amino acid tryptophan) among women with major depressive disorder who hadn’t experienced improvement with with selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) drugs.4 Depression scores declined by an average of 60% from pretreatment values after treatment with 5 grams of creatine monohydrate daily and 100 mg of 5-HTP twice daily for eight weeks.

Research suggests that creatine may be particularly effective in women. In depressed women with methamphetamine dependence, eight weeks of daily supplementation with 5 grams of creatine monohydrate resulted in a decrease in depression and anxiety scores as early as the second week of treatment and a reduction in methamphetamine-positive urine drug screens of greater than 50% by week six.2 Treatment increased brain phosphocreatine concentrations, which are reduced in treatment-resistant depression.

“The exact antidepressant mechanism of creatine is not clear, but one possible explanation involves its role in cellular energy metabolism given that accumulated evidence suggests that altered cellular energy metabolism is involved in the pathophysiology of depression,” the authors write. “Since creatine plays a critical role in cellular energy homeostasis, treatment with it might improve cellular energy metabolism.”

A placebo-controlled study that included adolescent girls with SSRI-resistant major depressive disorder found that eight weeks of daily creatine monohydrate supplementation increased mean frontal lobe phosphocreatine levels from pretreatment values, while levels in the placebo group declined.5 Higher phosphocreatine levels were correlated with lower depression scores. The authors note that converging lines of evidence indicate that mitochondrial dysfunction and altered brain bioenergetics could contribute to the etiology of depression. They further indicate that, in mitochondria, phosphocreatine is reversibly converted during the creatine kinase reaction into ATP (adenosine triphosphate) and creatine and that neuronal energy demands are met through a shift in reaction equilibrium, which is designed to keep brain ATP concentrations constant.

In a randomized, double-blind trial that included 52 women with major depressive disorder, participants who received creatine for eight weeks experienced greater improvement in depressive symptoms than those in the placebo group. Women who received creatine also experienced improvement in brain energy metabolism and network organization, which the authors of the report suggest may partly underlie its efficacy.6

Closing Thoughts

While creatine could offer a glimmer of hope to many adults with treatment-resistant depression, those who are being helped by antidepressants should not attempt to replace their drug regimen with creatine.

Supplementation with creatine is not suggested for depressed children or pregnant and lactating women. Individuals who are experiencing depression are advised to first consult their physician to determine the form of therapy that is right for them.

References

  1. Institute for Quality and Efficiency in Health Care. 2017 Jan 12. Depresson: How effective are antidepressants? PubMed Health. Retrieved from https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0087089/ Accessed 29 Jul 2018.
  2. Hellem TL et al. J Dual Diagn. 2015;11(3-4):189-202.
  3. Roitman S et al. Bipolar Disord. 2007 Nov;9(7):754-8.
  4. Kious BM et al. J Clin Psychopharmacol. 2017 Oct;37(5):578-583.
  5. Kondo DG et al. Amino Acids. 2016 Aug;48(8):1941-54.
  6. Yoon S et al. Biol Psychiatry. 2016 Sep 15;80(6):439-447.

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