Benefits
Muscle soreness after a half marathon
In a single small study of about 25 healthy runners who took 400 mg a day for 8 weeks of training and the week after a half marathon, quadriceps, hamstring and knee soreness were lower than placebo on day 1, and WOMAC pain and daily activity scores on days 1 and 3. Calf soreness and stiffness did not differ. A larger 12 week knee trial found no benefit over placebo.
Knee comfort and function over 12 weeks
In 135 adults with knee osteoarthritis, 400 mg a day for 12 weeks did not improve WOMAC pain, stiffness or daily function, discomfort ratings, rescue pain reliever use, range of motion or walking distance more than placebo; all groups, placebo included, improved. A glucosamine plus chondroitin group was included, but this does not show the two work equally. Unigen funded the trial.
Urine CTX-II, a cartilage breakdown marker
In the same 12 week knee trial, the change in urine CTX-II, a fragment released when type II collagen in cartilage breaks down, differed between the blend and placebo. This is a lab marker, not a measure of the joint or of symptoms, and the trial found no matching change in pain or function.
Blood redox markers after a half marathon
In the runner trial, a blood test of oxidative stress was lower and a test of antioxidant reserve higher than on placebo 6 days after the race, but not on day 1. These are markers measured in one small study; they do not show less muscle damage.
COX and LOX enzymes and rat joint models (lab and animal work)
In test tubes the blend inhibited the COX-1, COX-2 and 5-LOX enzymes that make inflammatory messengers. In rats it reduced paw swelling and pain sensitivity, and in rat arthritis models it lowered inflammatory markers and cartilage damage. These are laboratory and animal results, all from Unigen scientists.
Mechanism of action
COX and 5-LOX inhibition (laboratory data)
In enzyme assays the blend inhibited COX-1, COX-2 and 5-lipoxygenase, the enzymes that make prostaglandins and leukotrienes, with half-maximal concentrations of 20.9, 49.2 and 11.1 micrograms per milliliter. Whether amounts reached in people after a 400 mg dose do this has not been measured. In the 12 week knee trial, blood TNF-alpha did not change.
Cartilage and inflammatory signals (animal data)
In rats with chemically or collagen-induced arthritis, oral UP1306 lowered pain sensitivity, cytokines such as IL-1 beta, IL-6 and TNF-alpha, cartilage-degrading enzymes and urine CTX-II, and preserved cartilage on microscopy. The doses were 50 to 500 mg per kg of body weight, and the studies came from the maker's laboratory.
Catechins and mulberry root bark flavonoids
The Acacia extract supplies catechins and the mulberry root bark extract supplies stilbenes and prenylated flavonoids. In an ex vivo cartilage test the two extracts together protected proteoglycan more than either alone, which is the maker's stated reason for blending them. This has not been tested in people.
Clinical trials
Randomized, double-blind, placebo- and active comparator-controlled parallel trial; UP1306 400 mg a day (four 100 mg capsules), glucosamine hydrochloride 1,500 mg plus chondroitin sulfate 1,200 mg a day, or placebo for 12 weeks; acetaminophen allowed as rescue medication; registered ISRCTN15418623; funded by Unigen Pharmaceuticals through a restricted grant to the contract research organization QPS, which employed the first author; no Unigen employee authors (Kalman et al. 2017, J Nutr Metab)
135 adults aged 35 to 75 with knee pain for at least 6 months, Kellgren-Lawrence grade I to III and a discomfort rating of at least 6 out of 10 (45 per group; 43, 44 and 41 analyzed); about three quarters women and nearly all Hispanic.
The stated aims, WOMAC pain, stiffness and daily function, discomfort ratings and rescue medication use, did not differ between groups over 12 weeks (WOMAC pain fell 51% on UP1306, 45% on glucosamine plus chondroitin and 46% on placebo, p = 0.753; less rescue use on UP1306 than placebo in the first month was a nonsignificant trend, p = 0.066); range of motion, walking distance (p = 0.183) and TNF-alpha also did not differ overall, and knee extension change to day 28 favored placebo (p = 0.042) and the comparator (p = 0.018) over UP1306. WOMAC pain change to day 56 favored UP1306 over the comparator (p = 0.048) but not at 12 weeks, stiffness favored placebo at day 14, and the change in urine CTX-II differed from placebo at 12 weeks (p = 0.029). Adverse events were 15 on UP1306, 10 on the comparator and 18 on placebo, none serious. Because UP1306 did not beat placebo, the comparator arm cannot show that it works as well as glucosamine plus chondroitin.
Randomized, double-blind, placebo-controlled parallel trial at one center (GLH Nutrition, Utah); AmLexin 200 mg twice daily for 8 weeks of training and 1 week after a half marathon; per-protocol analysis without stated correction for multiple comparisons; no registry number reported; three of five authors are Unigen employees, the paper has no conflict of interest statement and thanks the owner of Unigen for supporting the studies (Yimam et al. 2018, J Exerc Nutrition Biochem)
30 healthy, active adults aged 18 to 70 (15 per group); 25 completers are analyzed in the methods (12 AmLexin, 13 placebo), while the abstract reports 26.
WOMAC pain and daily activity scores were lower than placebo on days 1 and 3 after the race (p < 0.05); total WOMAC was not different on day 1 (p = 0.08) and stiffness did not differ. Quadriceps, hamstring and knee discomfort ratings were lower on day 1; calf discomfort was not (p = 0.06). A redox test showed lower oxidative stress and higher antioxidant reserve than placebo on day 6 but not on day 1. The abstract describes redox benefits on days 1 and 6, but the results text reports a significant difference only on day 6. Eight symptom scores were compared on each of 6 days without correction, so only some of many comparisons reached significance. Side effects were not reported. A larger 12 week trial in knee osteoarthritis found no symptom benefit over placebo.