Zinc and Copper are 2 key minerals needed joint and overall health that are often in low amounts in the diet so we have added it to formula 2 in amounts that won’t exceed safe limits if you supplement with this in your multi-vitamin. 

  Boswellia serrata, also known as Indian frankincense, is one of the ancient and most valued herbs in Ayurveda. Boswellia inhibits the pro-inflammatory enzyme 5-LOX. Clinical trial: 30 patients received Boswellia Serrata 50% extract 333 mg 3 times a day for 30 days had a reduction in pain of 90% and improvement in ROM of 80%. 

Mangosteen is a tropical plant native to Southeast Asia. The fruits are consumed as food and also used in traditional medicine to treat skin infections, wounds, and diarrhea. Mangosteen juice is marketed as a health drink and the pericarp, or fruit hull, is used in dietary supplements for its antioxidant activity. Preliminary data show that xanthones, bioactive compounds in mangosteen, exhibit antibacterial, antifungal, anti-inflammatory, antiatherosclerotic , anti-asthmatic, antiangiogenic, cytotoxic (kills cancer), aromatase-inhibitory, and anticancer properties. [1]

• Clinical trial using 500 mg/day of men and women over age 55 with knee pain showed an average reduction in knee pain of 52% at the 28 day mark. [2]
• The xanthones found in mangosteen are being demonstrated to reduce inflammation by inhibiting the body's production of the COX-2 enzyme and blocking the process that leads to inflammation. [3]
• Alpha-Mangostin protects rat articular chondrocytes against IL-1β-induced inflammation and slows the progression of osteoarthritis in a rat model [4]

1. https://www.mskcc.org/cancer-care/integrative-medicine/herbs/mangosteen
2. https://www.researchgate.net/publication/265786492_Consumption_of_Mangosteen_Fruit_Pulp_Powder_MX3_provides_beneficial_effect_on_knee_discomfort_not_associated_with_injury_A_double_blind_placebo-controlled_pilot_clinical_study
3. https://www.naturalhomecures.net/mangosteen/science-xanthones/alpha-mangostin-and-gamma-mangostin
4. https://pubmed.ncbi.nlm.nih.gov/288

 Milk Thistle has been used for centuries to treat liver and spleen problems. But it is also a powerful anti-inflamatory with studies showing that 300 mg/day worked better than piroxicam or meloxicam both nsaids. With Silymarin reducing inflammation components by more than 50% in patients with OA, and the piroxicam and meloxicam having minimal to no affect. It also has anticancer properties.

    A powerful anti-inflammatory reducing COX2 by 30% and inhibit IL-1β-induced production of nitric oxide (NO) and PGE2 by 70% in chondrocytes, which cause the degradation of cartilage. It also has anticancer properties with multiple studies showing that pomegranate extracts inhibit the proliferation of breast cancer cells and even stimulate the programmed cell death of breast cancer cells. Pomegranate seed oil contains punicic acid, an omega-5 long chain polyunsaturated fatty acid that has been shown to inhibit breast cancer proliferation. Further research suggests that pomegranate juice may also slow the growth of prostate cancer, the leading cancer for men in the U.S. In a study of male subjects with recurrent prostate cancer and rising prostate-specific antigen (PSA) levels, researchers found that taking pomegranate juice extract significantly slowed the rate at which PSA was rising. Other studies have found that certain compounds in pomegranate juice show potent anti-tumorigenic effects and inhibited the growth of prostate cancer cells in the laboratory. It is also an aphrodisiac because it keeps testosterone from turning into estrogen, it helps lower blood pressure by 15%, and helps remove atherosclerotic plagues by 30%.

MSM is an organic source of sulfur and a relative of DMSO, the infamous solvent
ointment used on racehorses with joint pains. Fifteen percent of DMSO, whether taken internally
or topically, is converted into MSM. Because sulfur is necessary for the formation of connective
tissue, and because MSM is 34 percent organic sulfur, MSM has been widely studied for its use in arthritis and other complications of joint inflammation.
MSM is an organic source of sulfur that is found in plants but is lost with heating or freezing during food preparation. Because sulfur is necessary for the formation of connective
tissue, and because MSM is 34 percent organic sulfur, MSM has been widely studied for its use in arthritis and other complications of joint inflammation. Sulfur is found in cartilage and collagen. Because of MSM's sulfur content; it is used by the body to maintain normal connective
tissues. MSM is an important source of sulfur, but also has unique properties related to its
chemical structure and biological activities. MSM has many health benefits such as natural pain killer, antioxidant, and anti-inflammatory, chemopreventive properties, prostacyclin (PGI2)
synthesis inhibition, anti-atherosclerotic action, and free radical scavenging activity [1,2,3].
MSM has been shown to effect inflammatory conditions such as rheumatoid arthritis and lupus
[4.5]. For more info on MSM go to www.msm-info.com.
The natural level of MSM in the circulatory system of an adult human male is about 0.2
mg/kg. Normal adults excrete 4 to 11 mg MSM per day in their urine. Several studies suggest
that the systemic concentration of MSM drops in mammals with increased age, possibly as a
result of changing diet or body metabolism. Some research suggests that there is a minimum concentration of MSM that must be maintained in the body to preserve normal physiological function and the molecular structure of our musculoskeletal systems. Low concentrations of MSM in our bodies have been linked with unspecified complaints of fatigue, depression, high
sensitivity to physical and psychological stress, and with a large number of degenerative
diseases.
Sulfur is the fourth most abundant mineral in the body, after calcium, phosphorus, and
magnesium. It is an important component of vital amino acids like methionine and taurine; co-
enzymes like thiamin, biotin and coenzyme A; and major antioxidants like glutathione, cysteine and alpha lipoic acid.
Sulfur also inhibits the various enzymes that destroy cartilage, like collagenase, elastase,
and hyaluronidase. As far back as the 1930s, researchers demonstrated that persons with
osteoarthritis (and rheumatoid arthritis for that matter) are commonly deficient in this essential nutrient. As a matter of fact, these decades-old impressions were confirmed recently in patients with rheumatoid arthritis. Of note is that the severity of the RA was directly correlated with the
sulfate level in both blood (serum) and joint (synovial) fluids [6].

Clinical Trials:

The first clinical trial by Usha and Naidu's 12-week trial (n=118), patients with knee OA
received either 1.5 g MSM, 1.5 g glucosamine sulfate, 1.5 g MSM plus glucosamine sulfate, or
placebo; significant decreases in the Lequesne Index were reported with MSM, glucosamine sulfate, and their combination . There was 73% reduction in pain with glucosamine group, 52%
with MSM group and 79% with combination MSM and glucosamine group; joint mobility, swelling, global evaluation, and walking time also improved. [7]
In another trial using a much larger dose of MSM, 6g/day. The differences between the
MSM and placebo groups were relatively small in the WOMAC subscales. In the MSM group
pain decreased by 14.6 mm (25.1%), and in placebo it decreased by 7.3 mm (13.2%) at 12 weeks. The difference in pain improvement was 7.3 mm (12%) between the MSM and placebo groups. For physical function, stiffness and total symptoms, the decreases in MSM group were
15.7 mm (30.4%), 10.1 mm (19.7%), and 13.4 mm (25.1%) and the decreases in placebo group
8.8 mm (16.7%), 6.5 mm (11.7%), and 7.5 mm (13.8%), respectively. The differences between
the groups were 6.8 mm (13.7%), 3.6 mm (8.0%), and 5.9 mm (11.3%) at 12 weeks,
respectively. [8]

References:
1. Ebisuzaki, K. Aspirin and methylsulfonylmethane (MSM): a search for common mechanisms,with implications for cancer prevention. Anticancer Res. 2003; 23: 453–458

2. Alam, S.S. and Layman, D.L. Dimethyl sulfoxide inhibition of prostacyclin production in
cultured aortic endothelial cells. Ann N Y Acad Sci. 1983; 411: 318–320

3. Beilke, M.A., Collins-Lech, C., and Sohnle, P.G. Effects of dimethyl sulfoxide on the
oxidative function of human neutrophils. J Lab Clin Med. 1987; 110: 91–96

4. Morton, J. and Moore, R. Lupus nephritis and deaths are diminished in B/W mice drinking 3%
water solutions of dimethyl sulfoxide (DMSO) or dimethyl sulfone (DMSO 2 ). J Leukoc Biol. 1986; 40: 322

5. Hasegawa, T. Suppressive effect of methylsulfonylmethane (MSM) on type II collagen-
induced arthritis in DBA/1J mice. Jpn Pharmacol Ther. 2004; 32: 421–427

6. Bradlley H., et al. Sulfate metabolism is abnormal in patients with RA. J Rheumatol 21:1192-6,1994

7. Usha, P. and Naidu, M. Randomised, double-blind, parallel, placebo-controlled study of oral glucosamine, methylsulfonylmethane and their combination in osteoarthritis. Clin Drug Invest.
2004; 24: 353–363

8. Kim LS 1 , Axelrod LJ, Howard P, Buratovich N. Waters RF. Efficacy of
methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial.
Osteoarthritis Cartilage 2006 Mar;14(3):286-94. Epub 2005 Nov 23.

The original discovery of ginger's inhibitory effects on prostaglandin biosynthesis in the early 1970s has been repeatedly confirmed. This discovery identified ginger as an herbal medicinal product that shares pharmacological properties with non-steroidal anti-inflammatory drugs. Ginger suppresses prostaglandin synthesis through inhibition of cyclooxygenase-1 and cyclooxygenase-2. An important extension of this early work was the observation that ginger also suppresses leukotriene biosynthesis by inhibiting 5-lipoxygenase. This pharmacological property distinguishes ginger from nonsteroidal anti-inflammatory drugs. This discovery preceded the observation that dual inhibitors of cyclooxygenase and 5-lipoxygenase may have a better therapeutic profile and have fewer side effects than non-steroidal anti-inflammatory drugs. 1

• Clinical trial using 250 mg extract of ginger showed a 38% reduction in knee pain while standing in OA patients at 6 weeks. JNC isn’t using an extract but the whole root powder. 

1. https://pubmed.ncbi.nlm.nih.gov/16117603/
2. https://onlinelibrary.wiley.com/doi/10.1002/1529-0131(200111)44:11%3C2531::AID-ART433%3E3.0.CO;2-J

Turmeric, revered in India as "holy powder," has been used for centuries to treat wounds and infections. Modern research now confirms many of its traditional uses, revealing that turmeric has powerful antioxidant, anti-cancer, antibiotic, and antiviral properties. Its key compound, curcumin, strengthens the immune system by scavenging harmful oxidants and free radicals. However, curcumin is poorly absorbed by the body, a challenge that can be mitigated by the inclusion of black pepper extract, which enhances absorption. Joint Nutra Care (JNC) leverages these benefits by incorporating curcumin at levels similar to those consumed by regular curry eaters in India.

The anti-inflammatory effects of curcumin have been demonstrated in studies comparing it to common painkillers like phenylbutazone and corticosteroids. In one study, curcumin outperformed phenylbutazone in reducing inflammation after surgery without the dangerous side effects associated with nonsteroidal anti-inflammatory drugs (NSAIDs). Another study involving patients with rheumatoid arthritis found that curcumin provided significant relief from morning stiffness and joint swelling compared to corticosteroids, again without harmful side effects. Curcumin also inhibits inflammatory enzymes like COX better than other commonly prescribed drugs, making it a safer alternative for long-term use.

In addition to its anti-inflammatory and immune-boosting properties, curcumin shows promise in preventing cancer, particularly in regions where turmeric is widely consumed. Studies have found that curcumin inhibits tumor growth and enhances the body’s ability to destroy cancer cells. It also has potential benefits for brain health, helping to prevent Alzheimer’s, and supports liver detoxification, heart health, and digestion. Furthermore, turmeric promotes healthy skin, aids in weight control, and boosts the immune system, making it a versatile natural remedy for overall wellness.
1. Bharat, B.A., et al. "Curcumin--Biological and Medicinal Properties,"

2. Satoskar R.R., et al. "Evaluation of anti-inflammatory property of curcumin in patients
with post-operative inflammation," Int. J. Clin. Pharmacol. Ther. Toxicol.: 24(12), 651-4, 1986.

3. Kotwal, G.J., et al. Natural Products and Molecular Therapy, First International
Conference, New York, NY: Annals of the New York Academy of Sciences, Vol. 1056, 2005.

4. Deodhar, S.D. et al., "Preliminary study on antirheumatic activity of curcumin," Indian J.
Med. Res.: 71, 632-634, 1980.

5. Liacini, S., et al., "Inhibition of interleukin-1-stimulated MAP kinases, activating protein-1
(AP-1) and nuclear factor kappa B (NF-kappaB) transcription factors down-regulates matrix
metalloproteinase gene expression in articular chondrocytes," Matrix Biol.: 21(3), 251-262,
2002.

6. Sarker, S.D., et al. "Bioactivity of Turmeric," Turmeric: The genus Curcuma; Medicinal and aromatic plants

Decrease inflammation in joints and throughout the body by activation of the NRF2 Pathway which activates 200 genes that: control inflammation, increase anti-oxidants, and elimination of toxins such as benzene. 1,2

Decrease activation of MMP’s, which are enzymes that destroy cartilage. 3,4

Increase Chondrocyte production of new cartilage. 5

Many other health benefits such reducing cancer rates. 5+ servings/week of broccoli (or other cruciferous vegetables) had decrease cancer rates by 40 to 60% depending on the type of cancer. One serving is about ½ cup of broccoli. Broccoli sprouts have 100x more of the active component called sulforaphane. The amount of broccoli sprouts in JNC is about equivalent to 1 serving of broccoli. 6

References:
   1.   https://onlinelibrary.wiley.com/doi/full/10.1002/art.38133
   2.   https://pubmed.ncbi.nlm.nih.gov/24671668/
  3.   https://www.sciencedirect.com/science/article/abs/pii/S089158491932431
   4.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4240673/
   5.   https://www.sciencedirect.com/science/article/abs/pii/S0891584919324311
   6.   https://youtu.be/zz4YVJ4aRfg?list=PLSGUpeBAVCuavHTxklDM_EpHIO75bWWty

• It is truly amazing the health benefits of Bromelain and Papain from controlling cancer and improving heart disease to helping with arthritis.1 
• These enzymes help break down a protein called fibrin that is deposited in joints by an over active inflammation response and can disrupt the healing process.
• A clinical trial of 77 adults with knee pain, using 200 and 400 mg/day Bromelain showed a reduction in OA symptoms of 41% and 59% respectively after 4 weeks 2. 
• In another study 103 patients with osteoarthritis of the knee were divided into two groups to receive 90 mg of bromelain three times a day or 50 mg of diclofenac (a non-steroidal anti-inflammatory drug) twice daily. The two interventions were equally effective at improving each of the measures tested: joint tenderness, pain, range of motion, swelling In addition, patients who used bromelain said they had less pain when at rest, as compared to diclofenac. 3
• In another trial on back pain patients showed a 20% reduction in back pain after 6 weeks using 2 Bromelain and Papain (250 mg total) compared to standard treatment of the NSAID aceclofenac.4
• Many studies have shown that bromelain has a positive effect on arthritis (osteoarthritis and rheumatoid arthritis)5 
• A clinical trial using 650 mg (turmeric, devils claw and Bromelain) showed a 44% reduction in symptoms of OA after 60 days. 6, 7
• Bromelain has been used as a food supplement alternative to nonsteroidal anti-inflammatory drugs (NSAIDs). 8

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534447/
2. https://pubmed.ncbi.nlm.nih.gov/12587686/
3. ncbi.nlm.nih.gov/pubmed/15278753
4. Pak J Pharm Sci. 2020 Jan;33(1(Supplementary)):371-378. Efficiency of proteolytic enzymes in  treating lumbar spine osteoarthritis (low back pain) patients and its effects on liver and kidney enzymes
5. Pavan R., Jain S., Kumar A. Properties and Therapeutic Application of Bromelain: A Review.  Biotechnol. Res. Int. 2012;2012:1–6. doi: 10.1155/2012/976203
6. Conrozier T., Mathieu P., Bonjean M., Marc J.F., Renevier J.L., Balblanc J.C. A complex of three natural anti-inflammatory agents provides relief of osteoarthritis pain. Altern. Ther. Health Med. 2014;20:3237. https://pubmed.ncbi.nlm.nih.gov/24473984/
7. Grover A.K., Samson S.E. Benefits of antioxidant supplements for knee osteoarthritis: Rationale and reality. Nutr. J. 2015;15:1. doi: 10.1186/s12937-015-0115-z. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700773/

Revers-e-vine is a type of resveratrol but more potent. Research shows that 100 mg of revers-e-vine gives a 50% (which is huge) increase in activation of the SIRT-1 longevity gene. The longevity gene helps to keep the whole body younger including our joints. Resveratrol is also an antioxidant, anti-inflammatory and has anti-cancer properties. It helps repair mitochondria and slows aging in mice. In the lab it down regulates production of cartilage degrading enzymes, and also stimulates chondrocytes. Revers-e-vine along with hydroxytyrosol has also been shown to reduce the loss of telomeres on the ends of chromosomes, and therefore have very important anti-aging benefits. 

Astaxanthin has been called the miracle supplement of the 21st century. It is a powerful antioxidant and 6000 times stronger than Vit C. But it is also a powerful anti-inflammatory: 2 to 8 mg reduces C reactive protein CRP by 50% and MMP-13 by 75% both very important inflammation markers. In OA and RA cartilage, MMP-13 production results in the loss of type II collagen, tensile properties, and structural integrity of the affected joint.

Hydroxytryrosol found in extra virgin olive oil is the most powerful antioxidant found to date, and believed to be one of the reasons for the health benefits of the mediterranean diet It has important benefits to joints by protecting chondrocytes from oxidative stress and stimulating chondrocytes to do there job.  
 

25 adults with early osteoarthritis of the knee were given one tablet of 50 mg/day of olive extract (10 mg HT) or placebo for 4 weeks. A significant diminution in pain was observed in the group after 2 and 4 weeks of HT treatment, pointing to HT as effective treatment to reduce pain in patients with osteoarthritis. HT also helps lower inflammation biomarkers, and helps with diabetes, high blood pressure and cancer.  

Takeda, R.; Koike, T.; Taniguchi, I.; Tanaka, K. Double-blind placebo-controlled trial of hydroxytyrosol of Olea europaea on pain in gonarthrosis. Phytomedicine 2013, 20, 861–864. [Google Scholar] [CrossRef] [PubMed]

Boron, an essential trace mineral, is linked to a variety of health benefits, particularly in relation to bone health and reducing the risk of arthritis and certain cancers. Studies show that countries with low dietary boron intake, like Jamaica, have higher arthritis rates (up to 70%), while nations such as Israel, where boron intake averages 10 mg daily, have significantly lower arthritis rates (0.7%). Supplementation with boron has shown promise in reducing osteoarthritis symptoms, with patients experiencing up to a 71% decrease in pain and a 75% reduction in stiffness after 8 weeks of taking boron.

Beyond joint health, boron plays a vital role in hormone regulation. Studies demonstrate that 6 mg of boron daily for six months can increase Vitamin D levels by 20%, DHEA-S by 56%, and free testosterone in men by 30%, while reducing estrogen in men by 40%. In women, estrogen levels can increase by over 100%. Additionally, boron-rich diets are associated with a lower risk of prostate, cervical, and lung cancers, particularly in women who smoke.

Boron’s benefits extend to reducing inflammation, as it lowers markers like high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor α (TNF-α) by up to 50%. It also boosts antioxidant enzyme levels, improving the body's defense against oxidative stress. These combined effects make boron a powerful agent in promoting bone health, enhancing wound healing, and providing anti-aging benefits.

References:

1. Environ Health Perspect. 1994 Nov; 102(Suppl 7): 83–85.doi: 10.1289/ehp.94102s783
Essentiality of boron for healthy bones and joints. R E Newnham

2. Integr Med (Encinitas). 2015 Aug; 14(4): 35–48. Nothing Boring About Boron Lara Pizzorno,
MDiv, MA, LMT corresponding author

3. Calcium Fructoborate: Plant-Based Dietary Boron for Human Nutrition in Journal of Dietary Supplements · January 2009