Clinical trials have been a touchy subject in the health and wellness industry. It’s not that supplement and functional-food manufacturers oppose rigorous inquiries into the details of their products’ efficacy; it’s just that, for a while there, the U.S. FTC was interpreting the “competent and reliable scientific evidence” standard that it requires of manufacturers to substantiate a structure-function claim to mean “at least two adequate and well-controlled human clinical studies.”
While the FTC appears to have dialed back somewhat on this interpretation, it’s understandable that it initially set industry back on its heels. After all, as any researcher will attest to, even one well-controlled human clinical study—to say nothing of two—is incredibly complex, time-intensive, not to mention expensive to do. Such randomized controlled trials (RCTs) take a long time and a large number of participants to carry out. And they aren’t even always appropriate—or necessary—for answering the questions or establishing the knowledge that researchers or industry seeks.
But there’s a reason the National Institutes of Health (NIH), the FDA, and other august bodies deem RCTs the gold standard of clinical research—several reasons, in fact. Some consider such large-scale, randomized, controlled human studies indispensable for revealing consistent, unbiased information about a supplement’s effects, allowing us better to determine appropriate dosing, understand a mechanism of action, and elucidate benefits. And, for those who require them, RCTs burnish the legitimacy of an industry that often finds itself on the defensive.
But perhaps most importantly, RCTs have the potential to improve lives. “This is the type of research that needs to get into the hands of doctors, so they can make use of it in their practice,” says Harry B. Rice PhD, vice president of regulatory and scientific affairs, GOED (Global Organization for EPA and DHA Omega-3s; Salt Lake City). “Solid proof can only be obtained by conducting well-designed clinical trials.”
Rice and others share their candidates for some of the most notable human clinical trials of the year.
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Consumers have long turned to botanical preparations to prevent or alleviate flu symptoms, but the clinical evidence supporting such preparations’ efficacy hasn’t always been ironclad. A randomized, double-blind, placebo-controlled clinical trial (1) comparing the effects of a product containing Echinacea (Echinacea purpurea) herb and root extract plus European elderberry (Sambucus nigra) juice or extract against the common prescription flu treatment oseltamivir (Tamiflu) adds one more mark to the pro-botanical column. The results of the trial—involving 473 patients spread across 29 medical practices in the Czech Republic—showed the herbal extract (Echinaforce Hotdrink; A. Vogel Bioforce AG, Roggwil, Switzerland) to be effectively equal to the prescription treatment in its therapeutic effects, with a similar number of participants in both the botanical and prescription groups exhibiting mild or no symptoms after one, five, and 10 days of treatment.
Mark Blumenthal, founder and executive director of the American Botanical Council and editor-in-chief of HerbalGram & HerbClip (Austin, TX), lauds the study as “one of the largest clinical trials ever published on an herbal preparation, and clearly one of the two or three largest of which I’m aware on Echinacea.” As such, he said, “This is yet another significant human clinical trial that helps to document the clinical benefits of this specific Swiss Echinacea extract.”
1. Rauš K et al., “Echinaforce Hotdrink versus oseltamivir in influenza: A randomized, double-blind, double dummy, multicenter, non-inferiority clinical trial,” Current Therapeutic Research, Clinical and Experimental. Published online April 20, 2015.
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Vitamin K2 MK7
More people die each year from cardiovascular diseases (CVD) than from any other cause of death, according to the World Health Organization (WHO). And the relationship linking CVD, diet, and circulating triglycerides and cholesterol levels is almost common knowledge among health-aware consumers and the medical and scientific communities alike. But the role of vascular health in the onset and development of CVD hasn’t been as well known, until now.
One study (2), published earlier this year in Thrombosis and Haemostasis, is helping to raise vascular health’s profile, as well as that of a form of vitamin K2 particularly suited to promoting it. The three-year study involved 244 healthy postmenopausal women aged 55 to 65 who took 180 mcg of a menaquinone-7 form of vitamin K2 (MenaQ7 natural vitamin K2 MK-7; NattoPharma, Oslo, Norway) or a placebo daily. Using pulse-wave velocity and ultrasound—measurements that indicate the blood’s ability to flow through the vessels—researchers determined that the vitamin K2 inhibited age-related arterial stiffening and improved vascular elasticity to a statistically significant degree.
While earlier population-based studies revealed an association between vitamin K2 consumption and cardiovascular risk, “this is the first study showing that long-term use of vitamin K2 in the form of MK-7 beneficially affects cardiovascular health,” noted Cees Vermeer, the study team leader and a researcher at Maastricht University in the Netherlands, in a press release.
2. Knapen MH et al., “Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women: double-blind randomised clinical trial,” Thrombosis and Haemostasis, vol. 113, no. 5 (May 2015): 1135-1144
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Easy to Stomach
Stomach distress can seem like an inevitability in a modern era of plentiful stressors and even more plentiful occasions to eat (often not very well). No surprise, then, that use of proton-pump inhibitors (PPIs)—drugs that reduce gastric-acid production—has grown. But PPIs have appeared in some studies to encourage small-intestine bacterial overgrowth (SIBO) that leads to diarrhea, abdominal pain and bloating. A randomized, double-blind, placebo-controlled trial (3) recently looked at the role of probiotic bacteria in ameliorating those symptoms.
One hundred subjects with gastroesophageal reflux disease (GERD)—56 men and 44 women ranging in age from 18 to 70—were treated with the PPI pantoprazole for six months and then randomized to receive either two daily doses of the probiotic Lactobacillus paracasei F19 (LP-F19) three days per week for six months, a similarly administered placebo, LP-F19 for the first three months followed by the placebo, or the placebo for the first three months and LP-F19 thereafter. The results of the multicenter trial “suggest that concomitant use of probiotics—most likely Lactobacilli strains—may reduce bowel symptoms such as bloating and flatulence but not abdominal pain in patients taking PPIs long-term,” says Donald J Brown, ND, managing director, Natural Product Research Consultants (Seattle).
Additionally, Brown finds it “interesting” that the probiotic was only administered twice daily for three days per week during the study. “It will be interesting in future clinical trials looking at probiotics for prevention of gastrointestinal symptoms to consider not only probiotic potency,” he says, “but also frequency of administration. Finally, clinicians should be asking if the rampant use of PPIs and subsequent SIBO might be one of the primary contributors to the rise in functional bowel disorders such as IBS.”
3. Compare D et al., “Lactobacillus paracasei F19 versus placebo for the prevention of proton pump inhibitor-induced bowel symptoms: A randomized clinical trial,” Digestive and Liver Disease, vol. 47, no. 4 (April 2015) 273-279
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The long-chain omega-3 fatty acid docosahexaenoic acid (DHA) has a reputation as a brain-health powerhouse—a logical conclusion, given its importance as a constituent of brain phospholipids. But the brain can’t synthesize DHA from scratch, which suggests that our bodies need to shuttle the fatty acid across the blood-brain barrier. Just how that happens has been something of a mystery until recently, when several studies identified the protein MFSD2A as the major transporter for DHA uptake into brain.
The first study (4) in 2014 used a mouse model to establish the protein’s role. But two subsequent studies (5,6) published in 2015 involved human subjects and significantly moved the ball forward in explaining how DHA makes its way into cerebral tissue, and what happens when that transport is stymied. “This is a huge discovery,” says GOED’s Rice, “and one that received minimal attention” from the media,” despite its far-reaching implications.
“For example,” Rice says, “in a condition like Alzheimer’s disease, where DHA decreases in the brain as the disease progresses, would it be possible to modify the transporter to increase DHA accumulation, which in turn may slow down or even reverse progression?” Future clinical trials may reveal the answer.
4. Nguyen LN et al., “Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid,” Nature, vol. 509, no. 7501 (May 22, 2014): 503-506
5. Guemez-Gamboa et al., “Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome,” Nature Genetics, vol. 47, no. 7 (July 2015): 809-13
6. Alakbarzade V et al., “A partially inactivating mutation in the sodium-dependent lysophosphatidylcholine transporter MFSD2A causes a non-lethal microcephaly syndrome,” Nature Genetics, vol. 47, no. 7 (July 2015): 814-817
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All in Your Head
Scientists know that omega-3 and omega-6 fatty acids are chemical precursors to endocannabinoids, eicosanoid compounds similar to the active component in marijuana. As such, the fatty acids have demonstrated pain- and anxiety-fighting, as well as neurogenic, properties in previous studies.
A team of researchers including Christopher E. Ramsden, MD, a clinical investigator at the National Institute on Alcohol Abuse and Alcoholism, at the National Institutes of Health, has on multiple occasions looked at how manipulation of dietary omega-3 and omega-6 fatty acids influences headache pain, and examined in a recent trial (7) whether a high-omega-3/low-omega-6 (H3-L6) intervention altered actual plasma levels of omega-3 and omega-6-derived endocannabinoids and, further, whether these changes yielded clinical improvements. The results: among the study’s 55 participants, the dietary intervention increased levels of omega-3 derivatives while reducing those of omega-6, with the changes in omega-3 derivatives—but not omega-6 derivatives—correlating with reductions in physical pain and psychological distress.
According to GOED’s Rice, “The number of people who’ve told me that they modified their omega-3 and omega-6 intake and no longer suffer any or as many debilitating headaches is staggering. Obviously, for some, this may be nothing more than a placebo effect, but the results of Dr. Ramsden’s research are compelling without the anecdotal evidence.”
7. Ramsden CE et al., “Diet-induced changes in n-3- and n-6-derived endocannabinoids and reductions in headache pain and psychological distress,” The Journal of Pain, vol. 16, no, 8 (August 2015): 707-716
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