OPTI-FLEX™
REGENERATIVE JOINT COMPLEX

(3 customer reviews)

$94.99

USEF & FEI COMPLIANT, SHOW SAFE

Every equine athlete at some point in time needs support for bone, joint & connective tissue breakdown. Daily accelerated maintenance & support with Opti-flex™ REGENERATIVE JOINT COMPLEX. Created with highly anti-inflammatory human pharmaceutical quality, organic & natural ingredients, you can expect real results. This is a restorative joint health formula.

30-Day Supply- Powder w/Scoop

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OPTI-FLEX GETS RESULTS

ALL INGREDIENTS ARE HUMAN QUALITY PHARMACEUTICAL GRADE

Will Not Test & Has Amazing Taste

OPTI-FLEX, our horse supplement for restorative joint health is a formula that is results and science driven for bone, joint, connective tissue health and support being highly anti-inflammatory. OPTI-FLEX is the only horse supplement for joint health, formulated the way OPTI-FLEX is. This is a highly anti-inflammatory and antioxidant blend loaded with natural, herbal and organic ingredients, perfectly blended, in a clinically proven formula, not to mention it also contains Zeolite, as one of the many key active ingredients in this formula.  Our blend is based on the newest cutting edge ingredients for a horse supplement or horse nutrition product. We don’t use ingredients because they have a big name and are generally recognized by the public because they are usually on every label.  We have taken a different path with the newest scientific discoveries for ingredients that actually work safely and get visible results in a unique horse supplement formula.

  • Has been proven to restore Collagen II.
  • Will support cartilage cell health for all horses.
  • Can slow or stop cartilage degradation.
  • Opti Flex is highly anti-inflammatory with Leucine and COX 2 inhibitors (blocking inflammation) and works to naturally reduce already existing inflammation, reduce pain, support ease of movement and will.  Just watch the results from this next generation formula.  Review our supplement facts panel & see how we are different.  
  • Can aid to jump-start the natural process for regeneration of healthy joints. This is the perfect formula when rehabbing horses from injuries, surgery, musculoskeletal issues, osteoarthritis, and tendonitis.

REFER TO OUR SCIENCE TAB FOR MORE INFORMATION

 

3 reviews for OPTI-FLEX™
REGENERATIVE JOINT COMPLEX

  1. maegan Sherrod (verified owner)

    Ill be honest I have my mare on all 3 products and love them all! My mare had a tendon injury a few years ago and I just came back to running barrels in January this year, she is now 14 years old and needed something to keep her joints going strong. Another great thing is she has loved it from point one and thinks it tastes great! Thanks Optimum Performance!
    Maegan Sherrod

  2. Carrie (verified owner)

    I first heard about Optimum Performance after my 8 year old mare double-bowed her back tendons. We put her on Optiflex along with my Arabian right away. Nine months later we started bringing her back and today she is winning the 1 D at barrel races! Both my horses love the taste and are stronger than ever. I am very diligent about keeping them on these supplements so they can keep competing and stay strong! Thanks Optimum Performance!!

  3. dipasqualegab (verified owner)

    I use this product on my 12 year old mare who runs barrels and tends to be a very picky eater. She absolutely loves the taste of this product and I have seen a drastic difference in her runs. Thanks Optimum Performance!

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Zeolite – it is an aluminosilicate whose open tetrahedral framework allows ion exchange and reversible dehydration.  Benefits of Zeolite for horses include: Improved nutrient digestion, reduced scours, it reduces cribbing (chewing on wood), it improves bone growth and it improves the color of your horse’s coat.

Calcium (from calcified seaweed) – Aids in metabolism and essential to muscles. For strong bones and teeth, and helps with blood clotting.  Deficiency signs include fragile bones and poor growth and muscular problems.

Glucosamine HCL – Glucosamine HCL is a marine sourced amino sugar.  It is found in the body as one of the building blocks of cartilage necessary for its production and growth.

Hyaluronic Acid – Hyaluronic Acid is a special protein occurring naturally throughout the horse’s body.  Its function in the body is, amongst other things, to bind water and lubricate moveable parts of the body such as joints and muscles. Some key features include: lubrication of inflamed joints, increased joint mobility, reduction of joint friction, and alleviation of joint pain during activity.

Leucine – Leucine is an essential amino acid.  This means that it must be obtained through the diet in adequate quantities to meet the body‘s needs.  Leucine is a member of the branched chain amino acid family, along with Valine and Isoleucine.  The three branched-chain amino acids constitute approximately 70 percent of the amino acids in the body proteins.  Leucine is obtained by the hydrolysis of protein by pancreatic enzymes during digestion and necessary for optimal growth in the youngest and for the maintenance of nitrogen balance in adults.  Leucine is not only a building block of protein; it is THE key essential amino acid of muscle metabolism.

Boswellia Serrata Extract – Boswellia for horses is a powerful painkiller and anti-inflammatory derived from the gum resin of the Boswellia Serrata tree.  Boswellia for horses is often referred to as nature’s ‘Bute’ – a reference to the equine medicine phenylbutazone (‘Bute’).  On its own – or in combination with other products – it offers a gentle, natural solution to ease inflammation and pain in hard-working equine joints.  Boswellia Serrata is gentle on the gastrointestinal tract and safe for long-term use, and has been shown to be very useful in maintaining normal colonic function.

Green Tea Extract – Green tea has demonstrated ability to lower total cholesterol and raise HDL (good) cholesterol in both animals.  Results from one animal study suggest that polyphenols in green tea may block the intestinal absorption of cholesterol and promote its excretion from the body.

Several animal studies have found that green tea polyphenols inhibit the growth of esophageal (throat) cancer cells.

Green tea has been used traditionally to control blood sugar in the body. Animal studies suggest that green tea may help prevent the development of type 1 diabetes and slow the progression once it has developed. Therefore, Green tea may help regulate glucose in the body.

Animal studies have shown that green tea helps protect against the development of liver tumors in mice. Results from several animal and human studies suggest that one of the polyphenols present in green tea, known as catechin, may help treat viral hepatitis (inflammation of the liver from a virus). In these studies, catechin was isolated from green tea and used in very high concentrations.

Studies suggest that green tea extract may boost metabolism and help burn fat.

Cats Claw Extract – A woody South American vine, Uncaria tomentosa or a preparation of its root bark, which has antiviral, immunostimulant, and anti-inflammatory properties.  Cat’s claw can affect the immune cells responsible for cellular immunity; promote systemic microbial balance, and support antioxidant activity and circulation.

Maca – The cultivation and consumption of the Maca root dates back to more than 3000 years ago.  This powerful super nutritious root grows at more than 12,500 feet above sea level on the foot of these ancient and sacred mountains. Maca favors reproduction, improves digestibility of food, efficiency in the utilization of oxygen, and is highly energetic.  These characteristics are of vital importance to creatures living in the highlands.  In normal atmospheric conditions these properties make maca a powerful anti-stress, energizing, sexual, reproductive and physical invigorator.

Skullcap – Skullcap has been used for more than 200 years as a mild relaxant and as a therapy for anxiety and stress. Native Americans as well as traditional European herbalists historically have used skullcap to relieve anxiety and nervousness. Skullcap derives its name from the cap-like appearance of the outer whorl of its small blue or purple flowers. It is a slender, heavily branched plant that grows to a height of 2 – 4 feet and blooms each July. The parts used for medicinal purposes are the leaves, which are harvested in June from a three to four year old skullcap plant.

Skullcap is one of the most widely used herbs for the nervous system. It is an herb with specific actions on the nervous system. In humans, it is used for PMS, migraines, disturbed sleep, seizures, drug addictions and physical or mental stress. Its properties are said to include sedation, anti-spasmodic, anti-convulsive, and vasodilation (expanding blood vessels).

Turmeric Root – A woodland plant (Hydrastis canadensis) of eastern North America, having small greenish-white flowers and a yellow root used in herbal medicine. A Strong Antioxidant, the active constituent in turmeric is known as Curcumin. It has been shown to have a wide range of therapeutic actions.  It protects against free radical damage because it is a strong antioxidant.  An antioxidant is a substance (such as vitamin E, vitamin C) thought to protect body cells from the damaging effects of oxidation. It reduces inflammation by lowering histamine levels and possibly by increasing production of natural cortisone by the adrenal glands. Curcumin seems to have a protective effect on liver tissue exposed to toxic compounds like liver-damaging drugs.  There are also test-tube studies showing inhibition of metastasis (uncontrolled spread) of melanoma (skin cancer) cells or lymphoma tumor cells.  This may be attributed to its antioxidant activity in the body.  Animal studies from Rutgers have shown a possible use in prevention of tumor development, as well.  Turmeric is now being found in blends that help support joint issues with animals.

Yucca Root – The yucca root has nutritional value and is a source of fiber and vitamins in your diet.  The yucca root was first used by Native Americans and may have significant medicinal properties to treat several health ailments.  It contains properties that may improve animal functioning.

Yucca schidigera is a medicinal plant native to Mexico.  According to folk medicine, yucca extracts have anti-arthritic and anti-inflammatory effects.  The plant contains several physiologically active phytochemicals.  It is a rich source of steroidal saponins, and is used commercially as a saponin source.  Saponins have diverse biological effects, including anti-protozoal activity.  It has been postulated that saponins may have anti-arthritic properties by suppressing intestinal protozoa, which may have a role in joint inflammation.  Yucca is also a rich source of polyphenolics, including resveratrol and a number of other stilbenes (yuccaols A, B, C, D and E).  These phenolics have anti-inflammatory activity.  They are inhibitors of the nuclear transcription factor NFkappaB. NFkB stimulates synthesis of inducible nitric oxide synthase (iNOS), which causes formation of the inflammatory agent nitric oxide.  Yucca phenolics are also anti-oxidants and free-radical scavengers, which may aid in suppressing reactive oxygen species that stimulate inflammatory responses.  Based on these findings, further studies on the anti-arthritic effects of Yucca schidigera are warranted.

Nettle Leaf – Nettle is a rich source of vitamin C as well as a source of iron, calcium and potassium.  Nettle may be used as a daily feeding supplement for lactating mares, laminitic ponies, arthritic horses and for cases of anemia and poor condition.  Nettle can be used as a tonic or immune booster.

Celery Seed – Widely grown as a vegetable and salad plant, the seeds of this plant are used to treat urinary, rheumatic and arthritic problems.  A good cleansing, mildly diuretic herb is useful in ridding the system of an accumulation of waste products.  An improvement in circulation of fluids encourages a horse to drink and sweat more easily.  Celery has a significant antiseptic action with carminative (warming) effects.

Black Cohosh Root – Black Cohosh preparations are derived from the root and rhizome of a shrub-like plant (Cimicifuga racemosa) also known as black snakeroot. The name black cohosh is derived from the dark color and the rough and gnarly structure of the root. (Cohosh is Algonquin for “rough.”) The plant is native to eastern forests of North America.

This herb is helpful for the relief of menstrual cramps and symptoms of menopause. It is a natural supplier of estrogen with clinical studies showing that extracts of black cohosh not only relieve hot flashes, but also depression and vaginal atrophy as related to women.

Mares will experience similar difficulties as women do.

Ginger Extract – One of the first medicinal agents to be recorded in Chinese history, Ginger effectively removes congestion from the lungs and modulates the immune system.

Alfalfa – Alfalfa is both unique and nutritive with 60% of the oil present being the highly desirable Omega 3 fatty acids.  Alfalfa provides all the essential minerals, trace elements and vitamins in forms that are readily absorbed in your horse’s digestive system.  Alfalfa balances the high calcium content of alfalfa with elevated phosphorus resulting in a metabolically sound horse.

Cane Sugar – Being rich in sucrose content, sugarcane has a very high-energy value compared to cultivated grasses like napier, guinea, etc.  Sugar cane helps store food energy.

Rice Flour – Made from brown rice.  The husk is removed and the raw rice is ground. Rice flour is a particularly good substitute for wheat flour when allergies prevent its use.

Silicon Dioxide – Used to protect horse bones and connective tissues.

Clinically Proven

The claims made in Opti-Flex™’s advertising, packaging and marketing materials are reasonable and otherwise supported by clinical and scientific research. At least two peer-reviewed and published scientific study articles are available in an open access format that anyone can download, and a third study completed is being prepared for publication.

Double-Blind, Randomized, Placebo Controlled, Parallel Group, Multi-Center Study

Opti-Flex™ was evaluated in a multi-center, double-blind, randomized, placebo-controlled clinical trial of subjects with joint health issues reported a restoration of function and form, and no deleterious effects were noted as compared to placebo controls. Compromised movement, flexibility and the discomfort associated with compromised joint function were all metrics of the clinical trial, which demonstrated clear benefits with Opti-Flex™ over placebo. Safety metrics included laboratory and self-reported assessments as well as observations by a physician. These results were published in a peer reviewed open access publication, meaning that anyone can download and read the entire scientific paper at no cost.1

Epigenomic Study—Opti-Flex™ Gene Expression Study in Human Cartilage2

Opti-Flex™ is the first nutritional supplement that has demonstrated itself to be chondroprotective and anti-inflammatory through epigenomic processes. In a gene expression study on the specific formula at issue, researchers evaluated the influence of Opti-Flex™ on the processes of cartilage destruction and repair. They also specifically analyzed the regulation of the epigenetic “switches” that determine which genes are activated and deactivated.

The epigenomic study revealed that Opti-Flex™ has anti-inflammatory properties based on its suppression of inducible nitric oxide synthase and cartilage matrix degrading enzymes. Specifically, Opti-Flex™ was shown to activate the genes responsible for growing new cartilage through the production of Type II collagen, glucosamine and chondroitin, while simultaneously suppressing the processes of inflammation and cartilage degradation.

The results of the Opti-Flex™ gene expression study have been published in a peer-reviewed scientific publication.

Metabolomic Study

Opti-Flex™ was also the subject of a metabolomic research study conducted in 2011.3

Optimum Performance was the first Equine company to test a product for joint health using Metabolomics. Metabolomics is the scientific study of cellular metabolism.

In the Opti-Flex™ metabolomic study, samples from cultured human cartilage explants (chondrocytes) were grown in vitro. The purpose of the study was to profile the metabolome of the samples that were treated with Opti-Flex™. There are fundamental disturbances in cellular metabolism in joint inflammation. When inflammatory agents were introduced into the cells it was discovered that upon inflammation, the cells began functioning improperly and using highly valuable amino acids like leucine as their energy source instead of glucose as they do in a healthy state. The glucose is instead converted into lactic acid which causes pain and sorbitol, which promotes cellular swelling. Use of leucine as an energy source during inflammation prevents the leucine from performing its normal function of promoting healthy muscle growth and repair. Upon treatment with Opti-Flex™, the cartilage cells went back to using glucose as their energy source, thereby again allowing leucine to promote growth and repair.

The study supports that Opti-Flex™ has a positive effect on cellular metabolism.

 Restorative Joint Health Formula

Epigenetic and metabolomic studies were performed on Opti-Flex™ in human cartilage and human cartilage cells. The epigenetic and metabolomic research on Opti-Flex™ demonstrate that it prevents the destruction and breakdown of human cartilage in the context of inflammation, and it also activates key genes that are responsible for repair of cartilage.4 Basic cellular metabolism is dysfunctional in inflammation and Opti-Flex™ is the first nutraceutical to show a restoration of normal cellular metabolism in human cartilage cells. No other agents are known to share this profile and you have not advised us of any other joint health formula that has been studied and shown to have restorative effects on basic biochemical pathways including joint health.

The production of collagen and glucosamine (chondroitin is a combination of the two) by human cartilage cells (chondrocytes) is tightly regulated by specific genes. The activity of these genes is suppressed by inflammation. In the studies, Opti-Flex™ restored normal activity of these genes, even in the presence of suppressive signals. Controlling the activity of these genes is done through epigenetic actions of transcription factors. The most important transcription factor associated with inflammation is NF-kB, and Opti-Flex™ was able to block the activation of NF-kB in response to inflammatory signals, and as such restored normal chondrocyte utilization of its genetic resources for maintenance of cartilage health. These results were published in a peer reviewed open access publication, meaning that anyone can download and read the entire scientific paper at no cost.

1 Miller MJS, Butler R. Relief of osteoarthritis with an herbal-amino acid supplement: A randomized double-blind placebo controlled trial. Advances in Bioscience and Biotechnology 2012, 3, 504-510

2 Akhtar N, Miller MJS, Haqqi TM. Effect of a herbal-leucine mix on the IL-1b-induced cartilage degradation and inflammatory gene expression in human chondrocytes. BMC Complementary and Alternative Medicine 2011, 11: 66.

3 Global Untargeted Biochemical Profiling of a Natural Anti-Inflammatory Supplement- Analysis of Chondrocyte Spent Media. Study by Metabolon.

4 Specifically, it reactivates the genes that code for the production of glucosamine and Type II collagen, which are the essential framework of the cartilage matrix.

 

OPTI-FLEX™ FORMULA STUDY

Relief of osteoarthritis with a herbal-amino acid supplement: A randomized double-blind placebo controlled trial 

Mark J.S. Miller* & Ross Butler 

University of South Australia, School of Pharmacy & Medical Sciences.

Email: Ross.Butler@unisa.edu.au , markjsm03@gmail.com

*Corresponding author: Mark JS Miller, PhD, MBA,FACN, CNS

Abstract

A redox active medicinal plant and L-leucine mixture (HLM) was investigated in subjects with established osteoarthritis of the knee in a multi-center, randomized, placebo-controlled, double-blind clinical trial. A total of 96 subjects with osteoarthritis were enrolled and randomized to either placebo (n=38) or HLM treatment group (n=38). The HLM group received a combination of Uncaria tomentosa (300 mg), Boswellia serrata (200 mg), Lepidium meyenii (1000 mg) and L-Leucine (700 mg) given as 3 capsules once a day. The placebo group received matching capsules with carboxymethylcellulose. The treatment period was 8 weeks, with assessments made at days 7, 14, 28 and 56. The primary outcome was reduction in total WOMAC score. VAS pain, tolerability, investigator assessments, use of rescue medication (acetominophen), and safety assessments of vital signs and laboratory assessments were included. Subject randomization was effective for age, gender and disease severity. In the placebo group 32/38 subjects completed the trial and for HLM 35/38. WOMAC scores (pain, stiffness, physical performance and total) steadily declined over the course of the 8 week study in both groups, but the magnitude was significantly greater for HLM (P<0.05). Total WOMAC was reduced 46.5% for HLM and 25.4 % for placebo. VAS pain was reduced 21.8% in the placebo group (p<0.002) but the changes were significantly greater (37.8% p<0.03) with HLM treatment. Investigator’s global assessment rating of good-excellent was 24/35 (69%) for HLM and 14/32 (44%) for placebo (P=0.05). Rescue medication consumption and tolerability were comparable for HLM and placebo. No safety issues were evident with either group. As expected a placebo effect was observed, nevertheless HLM was clearly more effective in relieving the symptoms of osteoarthritis. This HLM represents a safe and effective new approach to the management of osteoarthritis symptoms.

  1. INTRODUCTION

Osteoarthritis is the most common form of joint disease and reflects a chronic inflammation that over time can result in joint destruction including the loss of articular cartilage and exposure of underlying bone. This condition can cause a significant loss in the quality of life. Current therapeutic interventions are inadequate, largely because they focus on symptomatic relief and do not abrogate the underlying disease process nor stimulate repair processes that may restore joint health for a sustained period [1]. In laboratory studies we have determined that a combination of specific redox-active medicinal plants and the branch-chained amino acid L-leucine possessed characteristics that were attractive as a potential therapeutic agent for osteoarthritis [2]. HLM was found to activate the genes coding for aggregating cartilage proteoglycan (ACAN) as well as type II collagen (COL2A1), and maintained this heightened expression in the presence of IL-1b which otherwise suppresses these anabolic repair genes. In addition to activating these repair pathways, HLM was able to suppress catabolic pathways (inducible nitric oxide synthase, MMP-9 and MMP-13) and limit IL-1b induced cartilage degradation. Of the three medicinal plants used in the investigative product, Boswellia serrata and Uncaria tomentosa have well described redox-based actions on inflammatory gene expression through the transcription factor NF-kB [9-12]. On the other hand, the cruciferous vegetable maca (Lepidium meyenii) has been shown to promote the expression of the repair gene IGF-1 in human cartilage cells [14].

These attributes HLM warranted a clinical investigation to further explore its potential as a treatment for osteoarthritis, and is the focus of the present report. The intent of this study was not confirm the gene expression studies noted in isolated cartilage [2], but rather to assess HLM for symptom relief versus placebo in a randomized double-blind controlled trial. In addition to efficacy, the goals were to determine whether HLM was safe using extensive laboratory and vital sign assessments.

1.2 KEYWORDS

Osteoarthritis, dietary supplement, cat’s claw, L-leucine, boswellia serrata, maca, uncaria tomentosa, lepidium meyenii, inflammation, cartilage, flexibility, pain, quality of life, stiffness, arthritis, nutraceutical, natural product.

  1. METHODS

2.1 Clinical Trial Criteria

This placebo-controlled randomized double-blind multi-center clinical trial was conducted in Mumbai, India under approval of a centralized independent ethics committee ACEAS (Gujarat, India) and registered at clinicaltrials.gov. The conductance of the study was overseen by a contract research organization (Vedic Lifesciences Pvt. Ltd., Mumbai). Four sites were used and subjects were recruited with the following inclusion criteria: age 30-65 of either gender, osteoarthritis diagnosis according to ACR clinical and radiographic criteria, ARA functional class II or III, Kellgren Lawrence radiological severity of Grade II or III of the knee, and maximal visual analog score for pain on movement of between 40-80.

Exclusion criteria include knee pain from conditions other than osteoarthritis, a BMI >35kg/m2, arthroscopy of either knee within the past year, use of analgesics within 7 days of screening, use of corticosteroids or nutraceutical medications for osteoarthritis within the past 3 months. Pregnancy and evidence of major medical conditions, drug dependence and participation in another clinical study within the last 6 weeks were also exclusion criteria.

Withdrawal criteria included serious adverse events that posed serious risk for he subject, development of medical condition that could affect the outcome of the study or any other condition which in the opinion of the investigator justified withdrawal of the subject. Finally, major protocol deviations were grounds for withdrawal. A fixed randomization procedure using an algorithm (Stats direct version 2.70) was used to assign interventions to the participants after participants passed screening procedures and assessments.

2.2 Treatments

Placebo or the herbal-leucine mixture HLM, was administered as three capsules delivered once a day, in the absence of meals, for 8 weeks. HLM consists of a proprietary blend of cat’s claw (300mg, Uncaria tomentosa, Ashancariaâ), boswellic acid (200 mg, Boswellia serrata), maca (1000mg, Lepidium meyenii, Macandeumâ) and L-leucine for a total of 2200 mg per day. The L-leucine was pharmaceutical grade manufactured by fermentation and not digested waste proteins. The excipient was magnesium stearate 150mg. Placebo was carboxymethylcellulose (2350mg).

The primary efficacy variable was total WOMAC score, using a WOMAC scale that was modified for the target population by Chopra [3]. The index consists of 24 questions (5 pain, 2 stiffness, 17 physical function). The Likert scale version of the WOMAC index was used; each question was scored from 0-4 with 0 representing none and 4 indicating extreme.

The pain-visual analog score (VAS) was used to assess pain. Patient diaries and consultations with clinic physicians were used to determine progress at screening, baseline, and then days 7,14, 38, 56. A central accredited laboratory was used for laboratory biochemical analysis. CRO personnel made monitoring visits every month to ensure that data was collected as per protocol and GCP. An independent statistician reviewed all data and provided statistical assessments. A total of 122 subjects were screened and 76 randomized (n=38 for each placebo and HLM). With 35 subjects completing for HLM and 32 for placebo.

2.3 Statistical Evaluation

Statistical evaluation was performed by an independent statistician who was contracted by the CRO, Vedic Lifesciences, Pty., Ltd. Efficacy was assessed using “intention-to-treat” (ITT) data where appropriate, using ANOVA and a repeated measures test where appropriate. Investigator assessments summarized in contingency tables was assessed using the Pearson’s Chi-Square test. The statistical software program Stats Direct 2.70 was used. Significance was taken a probability at the 5% level or less.

  1. RESULTS

3.1 Subject Demographics

Subject demographics enrolled in the clinical trial are summarized in Table 1. Randomization was effective with characteristics being indistinguishable between the two groups. Baseline efficacy metrics were comparable in the two groups, Table 2. Compliance was comparable between groups and averaged >96%.

3.2 Total WOMAC – Primary Efficacy Variable

Osteoarthritis is well known to be sensitive to a placebo effect and this was evident in this trial with a steady reduction in total WOMAC with placebo treatment over the 56 day trial period. However, reductions in total WOMAC were significantly greater with HLM treatment. This was noted from day 14 through to day 56 (Figure 1) with HLM. On a percentage basis HLM resulted in a 46.5% in total WOMAC, with only 25.4% with placebo treatment at day 56.

3.3 WOMAC – Pain, Stiffness and Physical Function

Similar to Total WOMAC, assessments for pain, stiffness and physical function indicated that HLM was significantly more effective than placebo. These results are summarized in Figures 2-4. HLM resulted in significantly greater improvements than placebo for all metrics (P<0.05). Both placebo and HLM showed a time-dependent improvement although this was more pronounced with HLM.

3.4 VAS Pain

Pain, assessed with a visual analog scale, was indistinguishable at baseline between groups: placebo 59.7 ± 2.0, HLM 59.9 ± 1.7. VAS pain was reduced with both placebo and HLM treatments (21.8 vs. 37.8%, P<0.002) over the 8 week study period. However, the benefits were significantly greater with HLM (Figure 5, p<0.05).

3.5 Investigator’s Global Assessment of Efficacy

Categorization of the global assessment of efficacy used 4 categories – poor, fair, good and excellent. Combining the groups poor/fair and good/excellent HLM was marginally more effective than placebo (Table 3, p=0.05). HLM treatment had a 68.6% assessment of good-excellent in contrast to 43.8% for placebo.

3.6 Consumption of Rescue Medication

In accord with ethics committee directions the subjects had free access to the rescue medication, acetominophen. Consumption of the rescue medication was determined at each time period (days 7, 14, 28, 56. No difference was determined between placebo and HLM treatments (Table 4).

3.7 Responsiveness and Onset of Action

Exceeding a 20% change in symptom assessments is a commonly used metric for determining responsiveness and onset of action. The HLM group displayed an average reduction of pain (24%) and stiffness (22%) within 7 days and all assessments (pain, stiffness, physical function and total WOMAC) by day 14. By contrast placebo did not achieve a 20% reduction in total WOMAC until the conclusion of the study (day 56). These results indicate that HLM displayed a significantly greater magnitude of benefits with an earlier onset of action than placebo.

3.8 Safety Assessments

Safety assessments were comprehensive and included laboratory and measurements of vital signs. In terms of laboratory assessments there was no difference in the values noted with placebo or HLM for total white blood cells, RBC, hemaglobin, hematocrit, platelets, differential white blood cell counts, erythrocyte sedimentation rate, serum creatine, SGPT, and fasting blood sugar (Table 5). Vital sign assessments were also not distinguishable between placebo and HLM (Table 6). This includes pulse rate, systolic blood pressure and diastolic blood pressure.

There were 6 adverse events reported during the study. Of these 5 were of the mild to moderate category, and one was severe. There was a rise in serum SGPT in 2 subjects, one each in the placebo and HLM group. A rise in fasting blood sugar level was noted in 2 subjects in the placebo arm. There was a single report of nausea and vomiting in both the placebo and HLM group. Tolerability rating for HLM vs. placebo was fair in 3 versus 1, and good in 32 vs. 31.

  1. DISCUSSION

Osteoarthritis compromises the quality of life and is remarkably common condition with 12.1% of the US population aged 25-74 having osteoarthritis of at least one joint [4]. Age is a major risk factor and the limitations on physical performance and concomitant pain results in osteoarthritis being a major societal burden. Despite this burden and the high incidence osteoarthritis there has been little in the way of treatments that modify the disease course and alleviate symptoms. The current standard treatment is NSAIDs, which alleviate symptoms like pain but do not alter the course of cartilage loss and joint destruction. In addition, NSAIDs are associated with a high rate of gastrointestinal, cardiovascular and renal side-effects, which can be fatal [5].

Innovations that provide symptomatic relief as well as alter the course of the disease are truly needed and as an alternative to pharmaceutical approaches there has been considerable interest in the nutraceutical approaches.  Ingested glucosamine, which is a structural element of cartilage, has been one of the more popular and widely studied [4]. However, despite early encouragement recent studies suggest that there is little benefit to glucosamine over placebo. A major reason for the poor responsiveness to glucosamine, or its related more complicated polymer chondroitin, is the disconnect between ingestion and the insertion of these matrix elements into joint matrix.

Bioavailability at the joint level is one limitation. Chondroitin is poorly digested and ingested glucosamine is cleared by the liver; breaking down to its glucose and amine components [4]. A further concern is that this glucose burden may pose issues for diabetics and pre-diabetics [6,7]. Another problem that limits joint repair is that ongoing inflammation suppresses the genes responsible for repairing cartilage [1,2]. In other words, cartilage repair is limited in arthritis through the combined effects of activated catabolic processes and suppressed anabolic, repair mechanisms. Ingesting additional matrix substrate, like type II collagen or glucosamine, under these circumstances without an active process that inserts the substrate into the cartilage matrix, is an inherently inefficient process. For this reason clinical results observed with either glucosamine or hydrolyzed collagen supplements have yielded mixed results.

The test agent used in this clinical trial, the combination of medicinal plants and leucine HLM has an entirely different approach to the problem and possesses attractive disease modifying agent properties. In human cartilage explants and chondrocyte culture, HLM demonstrated unique attributes that limited the processes that cause cartilage breakdown while at the same time activating the genetic resources that determine cartilage repair [2]. This research was performed in human cartilage explants and cultured human chondrocytes treated with IL-1b to mimic inflammation. HLM was effective in suppressing major, catabolic processes in human cartilage, specifically, expression of inducible nitric oxide synthase, MMP-9 and MMP-13 [2]. The master protein switch controlling inflammation associated gene expression, NF-kB, was suppressed by HLM [2, 8]. This confirms what we and others have previously noted with the individual medicinal plant components [9-14]. Concomitantly, the release of glucosamine from the cartilage matrix was blocked by HLM despite the ongoing presence of IL-1b.

While HLM prevented cartilage breakdown by suppression of redox-sensitive gene activation, it was also able to promote the gene expression of critical repair genes – ACAN and COL2A1 [2]. In other words despite the presence of IL-1b, HLM was able to transform the chondrocyte gene expression profile from catabolic to anabolic and repair focused. The role of L-leucine has not been fully explored in human cartilage and joints. It is a known anabolic factor in skeletal muscle [15,16], and recently it was reported that L-leucine was consumed at an excessive rate as a metabolic fuel by inflamed human synovium [17], suggesting that joint inflammation has a central component that disturbed leucine actions and/or metabolism. However, the individual contribution of L-leucine to the benefits of HLM is unknown.

The benefits noted in those in vitro studies on human cartilage are affirmed and extended to therapeutic applications in osteoarthritis in this study. Of critical importance HLM was demonstrated to be safe. There were no differences in vital signs or laboratory-based safety assessments between HLM and placebo (Tables 5 & 6).

Efficacy in alleviating the symptoms of osteoarthritis was assessed using the WOMAC score, which measures pain, flexibility/stiffness and physical performance with the summary of all of these measurements becoming the Total WOMAC score. VAS pain was also used as an assessment of efficacy. For all of these metrics, HLM was significantly more effective than placebo. Osteoarthritis, like other painful conditions, has a well-described placebo effect [18]. This placebo effect can mask effective agents because of the high background noise, and large numbers of subjects is sometimes used to help distinguish efficacy of test agents from placebo. Rescue medication use is an example of another potential masking factor. However, the use of acetominophen as a rescue medication was comparable between placebo and HLM.

However, in this study it is very clear that the benefits of HLM were readily distinguishable from placebo and this was apparent very early in the clinical trial (Figures 1-5). Significant improvements in pain relief, stiffness and mobility and physical performance and comfort were noted with HLM. Blinded global assessments of the interventions (HLM vs. placebo) indicated that these benefits to the study investigators and co-ordinators (Table 3). This is not to state that a placebo effect was absent in this study. By contrast it was very evident, with placebo improving all metrics related to efficacy. However, in all cases HLM produced a response whose magnitude was significantly better than placebo.

By following the progress of benefits throughout the course of the 2 month study we are able to provide additional evidence distinguishing HLM from placebo. These time-related assessments also indicate that the ability to establish a benefit of HLM over placebo begins at 7 days and is emphatic after 14 days of consumption. Previous clinical trials on glucosamine and related matrix-based nutraceuticals suggest an onset of action of months. The earlier onset of action of HLM compared to matrix-based interventions is most likely explained by the combined actions of limiting ongoing inflammation initiated catabolism while optimizing repair mechanisms with HLM [2, 9-16].

  1. CONCLUSION

An investigational agent consisting of a combination of redox-active medicinal plants and the branch-chained amino acid L-leucine, was effective in comprehensively alleviating arthritis symptoms in subjects with osteoarthritis of the knee. HLM should be considered a safe and effective approach in the treatment of osteoarthritis.

  1. ACKNOWLEDGEMENTS

This clinical trial was performed the assistance of the contract research organization, Vedic Lifescience, Pty. Ltd., and was sponsored by Vital g-Netics, LLC.

Neither author has a conflict of interest; there is no fiscal relationship with the manufacturer of and compensation for the conductance of this research project nor the development of this manuscript. Both authors contributed to the study design, analysis and manuscript preparation.

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Table 1: Subject Demographics

Demographic CharacteristicsPlaceboHLM
Age (years)53.1 ± 8.954.1 ± 7.7
Gender  (F:M)18:2024:14
BMI26.5 ± 3.326.5 ± 3.1
ARA Functional Class (Class II : Class III)34 : 433 : 5
Kellgren Lawrence criteria (Grade 2 : Grade 3)29 : 926 : 12

Results expressed as mean ± SD. There was no statistical difference between groups

 

Table 2: Baseline Efficacy Variables

Baseline ValuesPlacebo (n=38)HLM (n=38)
WOMAC – Pain6.6 ± 3.47.3 ± 3.3
WOMAC – Stiffness2.8 ± 1.82.8 ± 1.5
WOMAC – Physical Function25.4 ± 11.429.
WOMAC Total34.8 ± 15.839.3 ± 13.4
VAS Pain63.2 ± 10.059.5 ± 10.0

Results expressed as mean ± SD. There was no statistical difference between groups.

 

 

Table 3: Investigator’s Global Assessment

Categorization of RatingsPlacebo (n=32)HLM (n=35)
Excellent & Good1424
Fair & Poor1811

P=0.05 Chi Square test placebo vs. HLM

 

Table 4: Rescue Medication Consumption

Rescue Medication ConsumptionPlaceboHLM
Days 0 – 701.4 ± 8.4
Days 7 – 141.9  ± 3.11.2 ± 2.3
Days 14 – 282.7 ± 3.62.3 ± 3.7
Days 28 – 565.2 ± 8.24.4 ± 6.9

Results expressed as mean ± SD. There was no statistical difference between groups.

 

 

Table 5: Laboratory Safety Assessments

VariablePlacebo BaselinePlaceboEnd of treatmentHLMBaselineHLMEnd of treatment
WBC x 103/cu.mm6.5 ± 1.36.7 ± 1.77.1 ± 1.67.3 ± 1.8
RBC million/cu.mm4.8 ± 0.64.8 ± 0.64.7 ± 0.64.6 ± 0.7
Hb gm/dl13.5 ± 1.513.5 ± 1.613.2 ± 1.713.2 ± 1.8
Hematocrit %40.9 ± 4.340.6 ± 4.440.5 ± 5.040.1 ± 4.8
Platelet 1000/cu.mm258.6 ± 53.9254.8 ± 65.7265.4 ± 60.1274.3 ± 73.5
Neutrophil %56.8 ± 7.959.4 ± 9.260.0 ± 10.363.9 ± 9.7
Lymphocyte %32.9 ± 7.531.0 ± 8.530.5 ± 9.027.7 ± 7.6
Eosinophil %4.0 ± 3.44.7 ± 4.03.6 ± 4.33.6  ± 4.1
Basophil %0000
Monocyte %6.2 ± 2.04.9 ± 2.25.9 ± 2.44.8 ± 2.0
ESR15.0 ± 7.719.1 ± 15.717.9 ± 8.619.4 ± 11.0
Serum Creatine mg/dl0.79 ± 0.170.86 ± 0.170.84 ± 0.180.91 ± 0.23
SGPT U/L39.7 ± 8.142.9 ± 14.237.7 ± 10.643.2 ± 15.2
Fasting Blood Sugar mg/dl95.0 ± 14.9105.2 ± 34.195.8 ± 13.498.4 ± 17.2

Results expressed as mean ± SD. There were no statistical differences between groups.

 

 

 

 

Table 6: Vital Signs

VariablesPlacebo BaselinePlaceboEnd of treatmentHLMBaselineHLMEnd of treatment
Pulse74.7 ± 6.275.3 ± 6.274.6 ± 5.775.4 ± 6.4
Systolic BP mm HG126.8 ± 11.3128.7 ± 11.9127.8 ± 12.1127.0 ± 9.9
Diastolic BP mm HG81.8 ± 6.383.3 ± 7.482.5 ± 7.181.9 ± 7.4

Results expressed as mean ± SD. There was no statistical difference between groups.

Figure 1: Changes in Total WOMAC Score

total womac score

Results expressed as change from baseline (mean ± sem). The * signifies a statistical difference from placebo of at least P<0.05

Figure 2: Changes in WOMAC Pain scores

womac pain

Results expressed as change from baseline (mean ± sem). The * denotes a statistical difference from placebo.

Figure 3: Changes in WOMAC Stiffness scores.

womac stiffness

Results depict the change from baseline (mean ± sem). The * represents a statistical difference from placebo of at least P< 0.05.

Figure 4: Changes in WOMAC Physical Function scores

womac physical function

Results depict the changes from baseline (mean ± sem). The * designates a statistically significant difference from placebo of at least P<0.05.

Figure 5: Change in VAS Pain

vas pain

Results depict the change in VAS pain score after 56 days as noted from baseline (mean ± sem). The * denotes a statistical significant difference from placebo (P<0.05).

 

Opti-Flex and L-Leucine

 

The addition of L-Leucine to Opti-Flex is one of several innovative aspects that help define the uniqueness of the product. More importantly it defines a truly superior understanding of the fundamental problem that is joint inflammation. You cannot have sustainable solutions unless you fully understand the core problems driving the condition and then address them.

At a superficial level we appreciate that L-Leucine is a branch-chained amino acid (BCAA), and the BCAA that is thought to be the most important for anabolic actions on skeletal muscle. Working through intracellular signaling mechanisms (primarily mTOR) it drives muscle to a response of growth and repair.

In inflammation however, there is a fundamental disturbance in these mechanisms and only recently have we begun to understand the impact on L-Leucine and BCAAs in general. Firstly, inflammation is a catabolic state, the opposite of anabolism. Tissue is broken down. Only after the resolution of inflammation does the repair and re-growth phase commence. These systems are tightly regulated at the gene activity (expression level), where inflammation turns off repair and anabolic genes, essentially limiting the effectiveness of mTOR pathways and hence the activity of Leucine.

So with an injury or chronic inflammation the effectiveness of L-Leucine is compromised. Traditionally we thought it was simply due to a brake on the effectiveness of mTOR. However, we have defined a more fundamental problem.

Using the new science of metabolomics we revealed that L-Leucine driven anabolism by a metabolic diversion. This metabolomic disturbance was revealed by analyzing the complete metabolome of human cartilage in the context of inflammation. This is a first – no other natural product has used metabolomics to define their role in joint inflammation.

What was noted was this:

  • Under normal conditions cartilage cells act like other cells and use almost exclusively glucose for energy
  • During inflammation basic cellular metabolism is disturbed, and glucose is directed away from energy production towards the production of lactic acid and sorbitol.
  • Sorbitol is involved in cellular swelling.
  • Energy demands, which are high during inflammation, are met by burning a different fuel, specifically the BCAAs, particularly L-Leucine.
  • This metabolic diversion is inefficient and blocks the anabolic actions of L-Leucine.
  • There are also other fundamental changes in metabolism but these are the most dramatic.
  • ALL of the metabolic derangements in human cartilage were COMPLETELY REVERSED by Opti-Flex. Even in the context of inflammatory signals, Opti-Flex ensured that human cartilage used glucose for energy and preserved L-Leucine for mTOR-driven anabolism

Let’s put it in perspective using a metaphor. If you consider the need to create cellular energy like heating a house, then the normal and preferred fuel is glucose. It is like firewood in a fireplace. Clean burning, efficient and effective.

In the context of inflammation you still need to heat the house but instead of using firewood, you start to chop up the furniture and throw that into the fireplace. Yes it will create energy and warm the house, but the fundamental question is “Is that the best thing to do?”

Clearly it is not. For starters you end up with no furniture and there are nasty waste products.

Understanding this new information on the basic fundamentals of inflammation in human cartilage was critical to the design of Opti-Flex. Indeed, it is different because you need it to be different because all the previous approaches have failed to address the fundamental problem of an altered metabolome. The derangements in cellular metabolism are corrected by reversing the divergent demands and correcting the genetic resources that are directing decision-making.

Combining L-Leucine with the botanicals that correct alterations in genetic switches ensures that not only are inflammatory mediators blocked but metabolic processes are back in balance and the fundamental machinery is working efficiently and effectively.

Importantly, L-Leucine alone cannot correct the defects in metabolism. Actually all leucine supplementation alone is feeding the machine that is operating incorrectly – in essence burning more furniture. It is the unique combination that corrects the metabolic pattern and ensures that an anabolic state is returned.

This is why Opti-Flex is different. It stems from research that dictates where the fundamental problems lie and defines innovative solutions to return the body to a state of balance and health.

FlexSure is the FIRST NUTRACEUTICAL PRODUCT in the world to use metabolomics and epigenomics to define and demonstrate why its approach is superior and to use these emerging sciences .

Superior results from Superior Science.

500-750lbs 1 scoop daily
750-1250lbs 2 scoops daily
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1500lbs and up 4 scoops daily