Shorts

Jule Klotter

Autologous Conditioned Serum for Osteoarthritis

Over the past decade, several professional athletes have sought autologous conditioned serum (ACS), known as Orthokine®, provided by German physician Peter Wehling in Düsseldorf, Germany, to treat osteoarthritis (OA). The serum, which is made from the patient’s blood, is reportedly more effective than conventional treatments and does not have the side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors. Athletes like Kobe Bryant and Alex Rodriguez have credited the treatment with letting them continue their careers. It’s easy to find lots of hype about Orthokine and plenty of skeptical blogs too—but few clinical studies. Many stories in mainstream news and online conflate ACS with stem cell therapy or platelet-rich plasma.

As a 2013 review from Spain explains, ACS is designed to inhibit interleukin 1β (IL-1β), the pro-inflammatory cytokine that appears to be responsible for cartilage destruction, characteristic of arthritis. The patient’s blood is incubated in a syringe that contains glass beads coated with chromium sulfate at 37˚C for 24 hours. Then, centrifuge produces a serum that has high concentrations of IL-1β receptor antagonist (IL-1βRa), the natural inhibitor of the inflammatory IL-1β. Pro-inflammatory cytokines, including IL-1β and tumor necrosis factor alpha (TNF- α), do not increase during incubation. The serum is injected into the arthritic joint. The authors report, “An increase up to 140 times the concentration of IL-1βRa during incubation for 24 hours can be detected.” In their 2016 article for Cytokine, Angelique Barreto and Timothy R. Braun in Oklahoma report being able to increase IL-1βRa levels by a 32-fold increase, on average, with just 30 minutes of incubation, making the technique usable as “a novel, on-site, point of service process (Arthrokinex™).”

Animal research indicates that increased IL-1βRa levels can address arthritic pain and joint degeneration, according to the Spanish review. During a 2011 study, for example, researchers induced OA in both temporomandibular joints of rabbits. Animals in the intervention group were then injected with human IL-1βRa in one joint while the controls received a saline injection. Joints injected with IL-1βRa displayed fibrocartilage articular thickening and an increase in chondrocytes (cartilage cells) at 12 and 24 weeks. The untreated side showed marked histological signs of degenerative OA at 24 weeks. TNF- α levels did not differ between the experimental and control groups.

The few clinical studies conducted so far have shown positive, but not stunning, results. A 2009 randomized, double-blind study, conducted by AW Baltzer et al, involved 376 people with knee joint OA. ACS-treated patients reported significant improvements in quality of life compared to those who received hyaluronic acid or saline injections in their joint. Although some patients with severe pain (measured by visual analogue scale) reported positive results, the authors indicate that ACS is most effective for patients with low or medium pain levels. A second clinical study, conducted by KG Yang et al in 2008, also reported better clinical outcomes in patients receiving six injections of ACS compared to those injected with saline placebo; but “the statistical difference is small.” In addition, one patient of the ACS-treated group (n=89) had to withdraw due to inflammatory reactions that occurred within hours of being injected, and another developed septic arthritis attributed to injection procedure; there was no evidence that the ACS sample was contaminated.

Dr. Wehling does not view ACS as the magic bullet for OA. In a 2012 New York Times article, he is quoted as saying, “’It has to be embedded in a good concept more broadly’…sleep, diet and conditioning are among the important components to go with the injections. ‘There’s no such thing as the one therapy that fixes everything.’”

Alvarez-Camino J-C, Vazquez-Delgado E, Gay-Escoda C. Use of autologous conditioned serum (Orthokine®) for the treatment of the degenerative osteoarthritis of the temporomandibular joint. Review of the literature. Med Oral Path Oral Cu Bucal. May 2013;18(3):e433-8.

Barreto A, Braun TR. A method to induce interleukin-1 Receptor Antagonist Protein from autologous whole blood (abstract) Cytokine. 2016;81:137-141.

Kulish N. Novel Blood Treatment Lures Athletes to Germany. NY Times. July 10, 2012.

Vitamin C and Respiratory Infections

Respiratory infections and pneumonia are known complications of scurvy, a potentially fatal condition caused by vitamin C deficiency; and research shows that vitamin C supplementation can prevent and treat respiratory infections. Unlike most other animals, humans lack an enzyme that allows them to make their own vitamin C; so we must rely on diet sources, such as citrus fruit and kiwifruit, or supplementation. According to authors of a 2017 review article, humans need at least 100-200 mg of vitamin C each day to prevent infection. (A medium orange contains about 70 mg, according to USDA.) But the authors also state that a body’s need for vitamin C increases under diverse conditions, including diabetes, exposure to cigarette smoke and air pollution, and the presence of infection, stress, and aging. Decades of research show that vitamin C is involved in multiple physiological processes, many of which affect the body’s ability to fight infections, in addition to maintenance of collagenous structures and wound healing,

Vitamin C is well known as a potent water-soluble antioxidant that not only scavenges reactive oxidants but also regenerates glutathione and vitamin E. It is also a necessary cofactor for the action of several enzymes, including those involved in carnitine biosynthesis (required for transporting fatty acids into energy-producing mitochondria) and synthesis of catecholamine hormones (eg. norepinephrine) and amidated peptide hormones (eg vasopressin). Moreover, vitamin C accumulates in leukocytes and promotes phagocytosis (engulfment of microbes) and generation of reactive oxygen species to kill pathogens. It is also used during the differentiation and maturation of T-cells. Given the many roles that vitamin C has in immune function, it is likely that maintaining adequate levels will lessen the risk of developing serious infections. Research has not, however, shown that vitamin C supplementation prevents colds altogether.

“Treatment of established infections requires significantly higher (gram) doses of the vitamin to compensate for the increased inflammatory response and metabolic demand,” according to the review authors. The review authors cite several studies in which vitamin C supplementation reduced symptom severity and lessened the time needed for recovery in elderly people hospitalized with pneumonia, particularly in those with low vitamin C plasma levels.

In a 2016 article, Amanda Bucher and Nicole White, PharmD, recommend starting vitamin C treatment within 24 hours of noticing the first sign of a respiratory infection and to continue treatment for no less than five days. They report that higher doses (about 8 g daily according to one study) appear to be more effective than lower.

Too much vitamin C, taken orally, can produce diarrhea, which resolves when dosage is decreased.

Bucher A, White N. Vitamin C in the Prevention and Treatment of the Common Cold. American Journal of Lifestyle Med. 2016;10(3): 181-3.

Carr AC, Maggini S. Vitamin C and Immune Function. Nutrients. 2017;9:1211.

Play and Aging

Very few studies have looked at the benefits of play and playfulness for adults. Research has shown that playtime is essential for children as a means of developing physically, encouraging a creative and problem-solving state of mind, and helping children learn how to get along with others. While working adults tend to reject play as a waste of time (unless it involves some form of competition), play may be an important key to healthy aging, according to Careen Yarnal and Xinyi Qian. Engaging in playfulness brings joy. It feeds and maintains friendships. It improves cognitive and psychological function and quality of life, all of which support healthy aging.

What constitutes play? Peter Gray, PhD, a research professor at Boston College, says “the characteristics of play all have to do with motivation and mental attitude, not with the overt form of the behavior. Two people might be throwing a ball, or pounding nails, or typing words on a computer, and one might be playing while the other is not.” Play is an activity we choose and want to do. Play involves freedom, freedom to engage or to quit, freedom to explore, to try, and to fail. When we engage in play, we agree to the “rules” or required parameters—and quit if the parameters don’t meet our needs and bring satisfaction. Dr. Gray says, “…adults who have a great deal of freedom as to how and when to do their work often experience that work as play, even (in fact, especially) when the work is difficult. In contrast, people who must do just what others tell them to do at work rarely experience their work as play.”

Play also has to do with enjoying the activity itself rather than wanting a specific outcome. Reading books because you enjoy the topic is play. Reading books simply to pass a test is not. “To the degree that we engage in an activity purely to achieve some end, or goal, which is separate from the activity itself, that activity is not play,” says Gray. While activities that involve creating an object, such as knitting an afghan or building a bookcase, do have a desired outcome, “the primary objective in such play is the creation of the object, not the having of the object.” Similarly, when winning a game becomes more important than playing the game—whether soccer, golf, or Monopoly—it begins to feel more like work and less like play.

Because play focuses on means, not outcome, people do not experience the stress of needing to succeed and are not inhibited by fear of failure. Play is, by Dr. Gray’s definition, a state in which the mind is active, alert, and not stressed—a state which allows experimentation and exploration. Play engages the imaginative, creative parts of our psyche, removing us from “serious” life and decreasing stress. From Dr. Gray’s description, the effects of play sound very like the practice of mindfulness: “The mental state of play is what some researchers call ‘flow.’ Attention is attuned to the activity itself, and there is reduced consciousness of self and time.” This state has physical and mental benefits.

Margarita Tartakovsky, MS, an associate editor at Psych Central, offers some ideas for adding play to your life. She suggests taking a “play history”: “What did you do as a child that excited you? Did you engage in those activities alone or with others? Or both? How can you recreate that today?” Did you like dancing or exploring the woods nearby? Did you have fun collecting rocks or drawing pictures? Another way to add play and its benefits to your life is to seek out playful beings. Young children have a gift for having fun, and the enthusiasms of companion animals can often lead their owners to non-stressed opportunities for play.

I never thought of myself as a particularly playful person, but Dr. Gray’s essay helped change the way I think about play. Recognizing that play involves freedom and focusing on process rather than outcome helped me realize how much I blend play with work. How can you add more fun and play to your life?

Gray P. The Value of Play I: The Definition of Play Gives Insights (blog). November 19, 2008. www.psychologytoday.com

Tartakovksy M. The Importance of Play for Adults. No date. https://psychcentral.com/blog/the-importance-of-play-for-adults/

Yarnal C, Qian X. Older-Adult Playfulness – An Innovative Cosntruct and Measurement for Healthy Aging Research. Amer J Play. January 2011;4(1):52-79.

Autophagy and Aging

Health and longevity depend upon how well cells can recycle worn-out and malfunctioning cellular parts and organelles in order to generate energy or make new cells. This recycling process is called autophagy. Yoshinori Ohsumi, who received the Nobel prize for medicine in 2016, discovered how certain genes code for proteins used to form autophagosomes. These sack-like structures are used to collect and transport “cellular junk” to lysosomes, where it is broken down into usable components.

Autophagy is imperative for life. It removes dysfunctional mitochondria and other organelles and provides needed components for new cells. Autophagy also increases natural human growth hormone production and helps balance insulin and leptin activity. Poor dietary habits (eg, too many refined carbs), sleep disruption, inactivity, and aging inhibit autophagy. Dysfunctional autophagy is associated with several age-related conditions, including Parkinson’s disease, type 2 diabetes, and cancer.

Interestingly, calorie restriction, which is known to increase longevity, is the most effective way to stimulate autophagy. Paul Fassa offers several methods for including fasting in one’s lifestyle. The easiest, and probably least disruptive to the system, is to restrict food consumption by eating during just six hours of the day: for example, first meal at noon and last meal ends at six, with no snacking thereafter. (This is not always possible, depending on one’s health problems.) Fassa says that coffee and epigallocatechin-3 gallate (EGCG), found in green tea, also stimulate autophagy, according to animal studies.

Tong and Hill say that some compounds, such as spermidine, stimulate autophagy and can “mimic” the longevity effects of calorie restriction. Spermidine, which consists of amino groups, is found in rice bran, soybeans, aged cheese, mushrooms, and broccoli. A 2016 animal study showed that spermidine induces autophagy in cardiac tissue and, thereby, reversed aging-associated heart dysfunction (Eisenberg T, et al. Nat Med. 2016:22:1428-1348). Studies like this are encouraging researchers to find ways to promote autophagy and, thereby, reverse age-related conditions.

Devlin H, Sample I. Yoshinori Ohsumi wins Nobel prize in medicine for work on autophagy. The Guardian. October 3, 2016.

Fassa P. Autophagy and Intermittent Fasting: Removing Waste from the Body and Cellular Regeneration for Better Health. Health Impact News. July 16, 2018.

Tong D, Hill JA. Spermidine Promotes Cardioprotective Autophagy. Circ Res. April 14, 2017;120(8):1229-1231.