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October 22, 2021

WARNING LETTER

Ref: CMS Case # 616778

Dear Mr. Evans:

This is to advise you that the U.S. Food and Drug Administration (FDA) reviewed your website at the Internet address https://store.appliedhealth.com in July-August 2021 and has determined that you take orders there for the Applied Health Solutions brand products B Complex, Daily Detox, CellRenewPRO, CellRenewSTS, and PowerZyme Prime, and the NutriBiotic brand products Grapefruit Seed Extract CapsulesPlus and Grapefruit Seed Extract Liquid Concentrate. We also reviewed your website at the Internet address https://appliedhealth.com, which directs consumers to your website https://store.appliedhealth.com to purchase your products. The claims on your websites establish these products are drugs under section 201(g)(1)(B) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 321(g)(1)(B)] because they are intended for use in the cure, mitigation, treatment, or prevention of disease. As explained further below, introducing or delivering these products for introduction into interstate commerce for such uses violates the Act. You can find the Act and FDA regulations through links on FDA’s home page at www.fda.gov.

Examples of the website claims that establish the intended use of the products as drugs include, but may not be limited to, the following:

B Complex product:

On the “Prevent MRSA Infection” blog post (https://appliedhealth.com/prevent-mrsa-infection/), which hyperlinks to the product webpage for B Complex:

• “Prevent MRSA Infection . . . Annihilate infections before they start -Strengthen Your Immunity[.] Anything that can be done to boost your immune system will benefit you when you come in contact with this bacteria. . . . make sure you are getting plenty of immune boosting vitamins. . . . B-complex . . .”

Daily Detox product:

On the Daily Detox product webpage (https://store.appliedhealth.com/collections/detox-cleansing-support/products/daily-detox-toxin-binding-agents):

• “Broccoli Extract – BroccoSinolate [an ingredient in Daily Detox] . . . rich in . . . glucosinolates . . . Glucosinolates . . . help lower cancer risks and protect against cardiovascular disease. Another benefit . . . is the ability to help fight bacterial, viral, and fungal infections.”

On the “Prevent MRSA Infection” blog post (https://appliedhealth.com/prevent-mrsa-infection/), which hyperlinks to the product webpage for Daily Detox:

• “Regular use of Daily Detox offers powerful antioxidant protection against seasonal colds and flu.”

• “NATURAL TREATMENT: Good riddance “SuperBug”! These nutrients contain anti-microbial and anti-bacterial properties: Applied Health’s Daily Detox . . .”

PowerZyme Prime product:

On the PowerZyme Prime ingredients webpage (https://appliedhealth.com/powerzyme-digestive-enzymes/powerzyme-ingredients/):

• “Lysozyme [an ingredient in PowerZyme Prime] . . . Documented in human studies to inhibit the growth of Candida albicans.”

• “Serratia peptidase [an ingredient in PowerZyme Prime] . . . exhibits well documented fibrinolytic (prevention of blood clots), anti-inflammatory, and anti-edematous (prevents swelling of tissues from water entrapment – edema) activities and lessens the viscosity of exudates (a fluid of protein and cellular elements that escapes blood vessels due to inflammation and settles in nearby tissues).”

On the “Chronic Candida Syndrome” blog post (https://appliedhealth.com/chronic-candida-syndrome/):

• “What causes Candidiasis? . . . Other contributing factors to Candida imbalance are . . . Lack of digestive enzymes . . .” [the phrase “digestive enzymes” hyperlinks to the PowerZyme Prime product webpage]

On the “Chronic Candida Syndrome Part 2” blog post (https://appliedhealth.com/chronic-candida-syndrome-part-2/):

• “Incidence of Candidiasis is rapidly increasing. Several reasons for this are: . . . Lack of proper digestive enzymes in our diet. . . . As always, we prefer to recommend more holistic methods for our readers. However, remember that it is important to rotate even natural therapies, because resistant strains of Candida mutate easily. . . . Nutrients and antioxidants that support the immune system are also important, such as: Digestive Enzymes . . .” [the PowerZyme Prime product is also referred to as “Digestive Enzymes” on the PowerZyme Prime product webpage]

Grapefruit Seed Extract CapsulesPlus product:

On the Grapefruit Seed Extract CapsulesPlus product webpage (https://store.appliedhealth.com/products/nutribiotic-grapefruit-seed-extract-with-echinacea-and-artemisia-annua):

• “It is effective against pathogens because it belongs to a family of compounds known as quaternary compounds.”

• “Additional information to consider on Grapefruit Seed Extract [an ingredient in Grapefruit Seed Extract CapsulesPlus] is available at: Grapefruit Seed Extract for Cold/Flu Season:
https://appliedhealth.com/grapefruit-seed-extract-rx-for-cold-and-flu-season/ . . . Prevent MRSA Infection: https://appliedhealth.com/prevent-mrsa-infection/ . . .”

Grapefruit Seed Extract Liquid Concentrate product:

On the Grapefruit Seed Extract Liquid Concentrate product webpage (https://store.appliedhealth.com/products/nutribiotic-grapefruit-seed-extract-liquid):

• “Additional information to consider on Grapefruit Seed Extract [an ingredient in Grapefruit Seed Extract Liquid Concentrate]: Grapefruit Seed Extract for Cold/Flu Season: https://appliedhealth.com/grapefruit-seed-extract-rx-for-cold-and-flu-season/ . . . Prevent MRSA Infection: https://appliedhealth.com/prevent-mrsa-infection/ . . .”

Grapefruit Seed Extract Liquid Concentrate and Grapefruit Seed Extract CapsulesPlus products:

On the “Prevent MRSA Infection” blog post (https://appliedhealth.com/prevent-mrsa-infection/):

• “NATURAL TREATMENT: Good riddance “SuperBug”! These nutrients contain anti-microbial and anti-bacterial properties . . . Grapefruit Seed Extract [an ingredient in Grapefruit Seed Extract CapsulesPlus and Grapefruit Seed Extract Liquid Concentrate]”

On the “Benefits of Grapefruit seed Extract” webpage (https://appliedhealth.com/benefits-of-grapefruit-seed-extract/), which hyperlinks to the Grapefruit Seed Extract CapsulesPlus and Grapefruit Seed Extract Liquid Concentrate product webpages:

• “Grapefruit Seed Extract (GSE) [an ingredient in Grapefruit Seed Extract CapsulesPlus and Grapefruit Seed Extract Liquid Concentrate] . . . Used as a . . . antimicrobial product, it is known to be highly effective for fighting infection . . . Even in studies comparing its effectiveness to chlorine bleach, isopropyl alcohol, and colloidal silver, GSE has been found to be superior as an antimicrobial.”

• “. . . research showing the effectiveness of GSE against AIDS.”

• “All over the world, GSE has been used for killing a wide variety of bacteria (such as: Salmonella, E. coli, Staph and Strep germs), viruses, herpes, parasites, and fungi, including Candida. It is effective against more than 800 bacterial and viral strains, 100 strains of fungus, as well as a large number of single-cell and multi-celled parasites.”

• “. . . the antimicrobial properties of GSE . . .”

• “. . . antifungal properties of GSE have made it an important part of successful anti-Candida programs – a fact that has linked the names Candida and Grapefruit Seed Extract.”

• “‘In the treatment of intestinal protozoan infections . . . [ellipsis in original] drugs are generally so toxic that they cannot be administered for prolonged periods of time, whereas GSE can be administered for weeks or months; prolonged treatment being essential for the cure of chronic protozoan infections . . . [ellipsis in original]’”

• “To aid in the anti-Candida treatment, . . . GSE should be taken between meals. . . .”

• “. . . a variety of other ailments can be helped by GSE, such as: . . .

  − AIDS – An increasing number of HIV positive people are able to improve their immune system by using GSE to fight viruses, bacteria, fungi, Candida, or parasites. . . .
  − Colds, flus, viruses – Take 10-15 drops, or 1-2 capsules/tablets, 3 times a day, at the first signs of cold or flu. . . .
  − Chronic Fatigue Syndrome – To generally build up immune system, gradually increase GSE amount to the recommended dosage for colds, flus, and viruses. . . .
  − Diarrhea – Use 15 to 20 drops in juice every four hours; no more than 60 drops per day. For parasites, higher doses may be necessary. . . .
  − Parasites . . .
  − Traveler’s Diarrhea (Montezuma’s Revenge) – Use 1-2 drops of GSE in a glass of water each day as a preventative. . . .
  − Ulcers . . .”

On the “Grapefruit Seed Extract Rx for Cold and Flu Season” webpage (https://appliedhealth.com/grapefruit-seed-extract-rx-for-cold-and-flu-season/), which hyperlinks to the Grapefruit Seed Extract CapsulesPlus and Grapefruit Seed Extract Liquid Concentrate product webpages:

• “Grapefruit Seed Extract [an ingredient in Grapefruit Seed Extract CapsulesPlus and Grapefruit Seed Extract Liquid Concentrate] RX for Cold and Flu Season”

• “A Must-Have For Every Home During Cold and Flu Season”

• “Whether it’s a sore throat, earache, viral infection, intestinal problem, or anything else related to a virus, fungus, or bad bacteria, if you are the main caregiver in your home, Grapefruit Seed Extract is a must-have for your cupboard.”

• “. . . it is ‘Grapefruit’ Seed Extract (abbreviated as GSE or GFSE) that works as a natural antibiotic with anti-viral, anti-bacterial, and anti-fungal properties.”

• Under the heading “Internal Uses”:

  − “Fight Colds, Flus, Viruses”
  − “Reach for the GSE at the first symptoms of flu or cold.”
  − “Traveler’s Diarrhea – As a preventative when traveling in areas with questionable water, mix 1 or 2 drops GSE in each glass of water, or on your toothbrush to disinfect and help prevent Traveler’s diarrhea.”
  − “Diarrhea – If you do experience a case of diarrhea, take 15 to 25 drops GSE every 3 to 4 hours in water or juice – no more than 75 drops per day. Or, 2 capsules/tablets (no more than 6 per day) every 4 hours.”
  − “Parasites . . . Use the same amount of GSE as for diarrhea, with possibly increasing to a maximum of 5 doses per day.”
  − “There have been anecdotal reports of GSE helping some serious illnesses, such as Chronic Fatigue Syndrome, AIDS, and even Cancer.”

• “There are many more uses for GSE. Once you have successfully used it for something simple, like fighting a cold, you may find yourself reaching for it, regularly, whenever you find a need for its anti-viral, anti-fungal, and anti-bacterial properties.”

CellRenewPRO product:

On the CellRenewPRO product webpage (https://store.appliedhealth.com/collections/joint-soft-tissue-support/products/cellrenew-pro-hydrolyzed-collagen-type-ii):

• “CellRenew PRO provides multi-dimensional nutritional components vital for repairing connective soft tissue (joints, skin, cardiovascular, etc.).”

On the CellRenewPRO supplement facts and monograph webpage (https://store.appliedhealth.com/pages/cellrenew-pro-defined):

• “CellRenew Pro is Ultimate Joint Repair”

• “CellRenew PRO provides multi-dimensional nutritional components vital for repairing connective soft tissue (joints, skin, cardiovascular, etc.).”

CellRenewPRO and CellRenewSTS products:

On the CellRenewPRO (https://store.appliedhealth.com/pages/cellrenew-pro-defined) and CellRenewSTS (https://store.appliedhealth.com/pages/cellrenew-sts-supplement-facts-and-monograph) supplement facts and monograph webpages:

• “CellRenew contains Hydrolyzed Collagen Type II derived from 100% pure chicken sternal cartilage. As an abundant source of naturally-occurring Hyaluronic Acid and Chondroitin Sulfates, Collagen Type II is easily absorbed to restore joint and cartilage health.”

• “It is an absorbable hydrolyzed collagen type II product . . . that . . . relieves joint discomfort and increases mobility.”

• Under the heading “Research”:

  − “Collagen Type II (CCII) [an ingredient in CellRenewPRO and CellRenewSTS] . . . can suppress pro-inflammatory activity to reduce joint discomfort and restore cartilage health. CCII from chicken sternal cartilage was shown to reduce chronic joint inflammation . . .”
  − “A three-month study recruited 60 patients with chronic joint inflammation to take CCII or a placebo. Results indicated CCII alleviated swollen and tender joints in the treatment group. Four patients in the treatment group had a complete remission of chronic joint inflammation.”
  − “Similarly, a pilot-study recruited female subjects with joint pain to take Hydrolyzed Collagen Type II for 42 days. Subjects reported a significant improvement in joint mobility and decrease in joint pain and stiffness.”
  − “CCII is evidenced to be effective among adolescents with chronic joint inflammation. A pilot-study administered CCII to 10 adolescent patients with chronic joint inflammation for 12 weeks. Eight patients experienced a reduction in swollen and tender joints. A similar pilot-study recruited nine adolescents with chronic joint inflammation to take an oral Collagen Type II, finding the supplement . . . reduced joint inflammation.”
  − “Chondroitin Sulfate (Component of Collagen Type II) [an ingredient in CellRenewPRO and CellRenewSTS] Naturally found in sternal chicken Collagen Type II, chondroitin sulfate has anti-inflammatory activity that reduces joint swelling, maintains synovial fluid levels, and spacing between the joints. Further, chondroitin sulfate reduces the proliferation of proteins to reduce joint inflammation.”
  − “A one-year study recruited 42 patients with knee pain to take chondroitin sulfate or a placebo. Subjects taking chondroitin sulfate had greater joint mobility and less pain, when compared to the placebo group.”
  − “A three-month study recruited 110 patients with knee pain to take chondroitin sulfate or a placebo finding supplementation improved knee function, reduced pain, and maintained joint space in the knee.”
  − “Researchers suggested chondroitin sulfate and glucosamine could repair and regenerate cartilage . . .”
  − “Hyaluronic Acid (Component of Collagen Type II) [an ingredient in CellRenewPRO and CellRenewSTS] . . . Studies have suggested hyaluronic acid has anti-inflammatory activity that suppresses pro-inflammatory and pain mechanisms in the body.”
  − “Researchers found that HA inhibited inflammatory cytokine activity in mice with inflamed joints. A similar study reviewed the effect of HA on acute and chronic inflammation in rats, finding HA suppressed inflammatory reactions . . .”

On the homepage for the https://appliedhealth.com website:

• “How do you help knee pain? . . . CellRenew PRO is Extreme Knee Protection”

• “CellRenew Additional Links . . . CellRenew Collagen Type II and Knee Pain . . . Is Collagen Type II A Cure For Arthritis And Heart Disease . . .”

• In the response to the question “What is CellRenew?”:

  − “Unlike other protocols for arthritis symptoms, whether prescription or natural, CellRenew is guaranteed for results.”
  − “It contains naturally occurring Hyaluronic Acid and Chondroitin Sulfate. The results of a human clinical trial using this material showed significant improvements in the reduction of joint swelling, tenderness, and pain, as well as successful increases in mobility.”

• In the response to the question “Who is a good candidate to take CellRenew?”:

  − “Although studies have shown that many different conditions respond to Collagen Type II, the conditions that have shown the greatest response are rheumatoid arthritis and osteoarthritis. If you have grown weary of traditional protocols that only cover-up symptoms and neglect to address the root cause, then you are an excellent candidate to begin a program of Collagen Type II.”
  − “CellRenew is also used as a preventative measure for athletes who . . . are looking for a way to maintain healthy joints prior to the onset of osteoarthritis.”

• In response to the question “What will it do for me?”:

  − “Collagen Type II (CTII) [an ingredient in CellRenewPRO and CellRenewSTS] has been suggested to offer significant benefits for some types of arthritis. . . . Rheumatoid arthritis (RA) is the most well known of the autoimmune types of arthritis. In the case of RA, the collagen in the joints is attacked.”
  − “Depending on the particular type of arthritis you experience, CTII goes to work in different ways. If you suffer from RA, CTII acts as an oral tolerization agent, instructing the body to stop the immune response to the collagen in the joints. . . . For those suffering from osteoarthritis, CTII provides the critical building blocks that restore a healthy state to the cartilage in the joints.”
  − “CellRenew is made from chicken sternal cartilage that contains the highest level of naturally occurring anti-inflammatory proteoglycans (Hyaluronic Acid and Chondroitin Sulfate A) of any other material tested, including shark cartilage. It is important to note that the combination of the proteoglycans and the Collagen Type II proteins . . . provide the building blocks required to rebuild lost cartilage to restore the joint to a normal state.”

• In response to the question “What do the studies show?”:

  − “The results of a recent double-blind, placebo-controlled, clinical trial has proved the benefits of Collagen Type II for treating the symptoms of pain and immobility associated with arthritis. . . . report an 89.9% positive response rate, within 45 days, for the participants who consumed at least 2000 mg of Collagen Type II per day.”
  − “[R]eported having successfully treated more than 50 patients, starting in 1974, with osteoarthritis, rheumatoid arthritis, psoriasis, and many other ailments. . . .”
  − “Of the different types of cartilage tested, the one with the highest level of Collagen Type II, anti-inflammatory proteoglycans (the healing properties) was chicken sternal cartilage. CellRenew is 100% chicken sternal cartilage.”

• In response to the question “What else is it good for?”:

  − “Besides the better-known associations with osteoarthritis and rheumatoid arthritis, it has also been suggested that Collagen Type II might benefit heart disease, psoriasis, progressive myopia, and some other autoimmune diseases.”

• In response to the question “How long before I improve?”:  

  − “Although some people have noticed an improvement with their symptoms after only a week or two of starting a CellRenew program, many take between 4 and 6 weeks. . . . some forms of arthritis symptoms tend to respond faster – on average – than other forms. For instance, we do know that rheumatoid arthritis sufferers have a tendency to respond faster . . .”

Under the heading “CellRenew Customer Stories” on the homepage for the https://appliedhealth.com website:

• “‘I have been taking CellRenew since May of 2003. . . . This product has kept my arthritis at bay. . . .’”

• “‘[T]hank you for the dramatic results I have experienced in the first three weeks of taking CellRenew. For the past twenty years, I have been living with severe lower back pain. I was diagnosed with a degenerative disc disorder in the L2, L3, and L4 vertebrae. . . . CellRenew has improved my quality of life one thousand percent.’”

• “‘Fourteen months ago – diagnosed with scoliosis, osteoarthritis of the spine and degenerative disc disease – my active life was gone . . . I was in excruciating pain most of the time. . . . On the xray [sic], my spine looked like a rock pile. . . . Enter CellRenew, and within one month, the improvement was incredible. That was four months ago. . . . I have my life back. I know that CellRenew works!’”

• “‘I wanted to tell you all about how thrilled I am with CellRenew. I have been taking CellRenew for just over a year now. I have not had a single ache or pain in at least 10 months. I have experienced no side effects, except for one good side effect. I have changed my eyeglass prescription, twice! Both times were for the better! My eyesight is improving. . . .’”

Under the heading “In the beginning…” on the homepage for the https://appliedhealth.com website:

• “Bill Evans, President, Applied Health . . . my lifestyle was finally catching up to me . . . due to rapidly progressing arthritis. . . . Instead of a future filled with the pursuit of my favorite activities, and dreams of conquering the Bucket List, I only saw the prospect of surgeries, painkillers, and physical therapy. I decided there had to be a better way than knee replacement and a cocktail of medications. A year later, in 1997, we started Applied Health and introduced our first Collagen-based, joint support product using hydrolyzed collagen type II . . . We called it CellRenew, and over 20 years later, we still have devoted users . . . [ellipsis in original] myself among them.”

On the “CellRenew Hydrolyzed Collagen Type II Technical Outline” webpage (https://appliedhealth.com/cellrenew-collagen-type-ii/cellrenew-technical-outline/):

• Under the heading “Key Product Highlights/Bullets”:

  − “CellRenew is so effective that the raw material has been awarded two United States Patents . . . for the treatment of connective tissue disorder, osteoarthritis, degenerative joint disease, joint defects, vascular disease, and cartilage injuries . . .”
  − “May help support proper inflammatory function due to its chondroitin sulfate content . . .”
  − “May possibly support proper wound healing due to its potent hyaluronic acid content . . .”

• Under the heading “Studies and Mechanisms of action”:

  − “CellRenew and its components can have a powerful impact on joints and conditions associated with abnormal joint function. One study [footnote omitted] published in 2000 entitled ‘Role of collagen hydrolysate in bone and joint disease’, reviews how collagen can be a powerful tool in helping with osteoarthritis and even osteoporosis. . . . Mechanism of action: The components of CellRenew . . . lower the chance for deterioration.”
  − “‘[H]yaluronan preparations have been shown to decrease pain and increase function in patients with osteoarthritis of the knee.’ Mechanism of action: Hyaluronic Acid seems to work through several mechanisms of action including restoration of more normal synovial fluid with improved viscoelasticity, effects on cartilage biosynthesis and degradation, anti-inflammatory effects, and direct analgesic effects.”

• Under the heading “Patent Claims”:

  − “2. A method for treating an individual with a connective tissue disorder . . .”
  − “3. The method of claim 2, wherein said connective tissue disorder is selected from the group consisting of degenerative joint diseases, joint defects, osteoarthritis, polychondritis, vascular disease, cartilage injuries, progressive myopia and Menier’s [sic] disease.”

On the “Effects of Collagen Type II For Subjective Pain Relief” webpage (https://appliedhealth.com/cellrenew-collagen-type-ii/hydrolyzed-collagen-clinical-trial/), which contains a hyperlink to the online storefront where the CellRenewPRO and CellRenewSTS products can be purchased:

• The following quote appears after a summary of a study on the effects of Collagen Type II (an ingredient in CellRenewPRO and CellRenewSTS) on the course of pain syndromes, including rheumatoid arthritic pain, osteoarthritis joint pain, post surgical joint pain, post traumatic pain, fibrositis, gouty arthritis, lumbosacral pain with/without radicular pain, and cervical spine pain with/without radicular pain: “‘The results were overwhelmingly positive for pain relief and the side benefits were remarkable! This product has changed my life significantly.’”

On the “Is Collagen Type II A Cure For Arthritis And Heart Disease?” webpage (https://appliedhealth.com/cellrenew-collagen-type-ii/collagen-type-ii-cure-arthritis-heart-disease/), which hyperlinks to the online storefront where the CellRenewPRO and CellRenewSTS products can be purchased:

• Under the heading “Collagen Type II [an ingredient in CellRenewPRO and CellRenewSTS] and Arthritis”:

  − “. . . 50 million Americans suffer from some form of arthritis, either rheumatoid or osteoarthritis, as well as a variety of other arthritic conditions. . . . Could it be that one nutritional medicine called collagen type II can ameliorate both disorders in an effective way?”
  − “It may turn out that the natural components of cartilage hold the greatest promise of ameliorating both arthritis and heart disease.”
  − “If collagen type II is derived from chicken sternal cartilage, from chicks six to eight weeks old, it contains the greatest number of anti-inflammatory and joint supporting proteoglycans. These proteoglycans include glucosamine sulfate which has over 30 years of double-blind, placebo-controlled studies indicating that it actually helps to rebuild the cartilage in arthritis joints.”
  − “[I]t contains a high concentration of chondroitin sulfate A, which is a powerful anti-inflammatory . . .”
  − “[C]ollagen type II also contains a powerful, newly discovered antioxidant proteoglycan called cartilage matrix glycoprotein (CMGP), which can help reduce the oxidative damage to the joint.”
  − “When people suffer from arthritis, there is a selective destruction of collagen type II in the joint cartilage itself. Scientists know that this particular component of cartilage is being attacked by white blood cells and somehow this activates the immune system in the rheumatoid arthritic patient to develop antibodies to collagen type II. This then sets up an immune response to all of the cartilage that is degenerating in the body. Thus, both wrists hurt, both knees hurt, the hips, the back, etc.”
  − “The question now becomes how does collagen type II turn off the immune system in the rheumatoid arthritic. The answer is that collagen type II’s effectiveness is accomplished through ‘oral tolerance.’”
  − “. . . investigate the side effects of chicken sternal collagen type II being fed to arthritic rats. . . . By the second or third months the rats no longer displayed any symptoms of arthritis. There was a profound amelioration of the disease.”
  − “. . . studied ten people with severe rheumatoid arthritis. They eliminated the standard therapies such as NSAIDS and methotrexate and fed the patients pure collagen type II derived from chicken sternal cartilage. At the end of the second month, six of the ten patients showed substantial improvement and one showed a complete regression of the disease that lasted 26 months with no side effects.”
  − “. . . conducted a phase II trial on 59 patients with, again, severe active rheumatoid arthritis. . . . What is interesting is that those who were off all drugs and taking collagen type II showed very significant stabilization and improvement, while those on placebos continued to deteriorate. In fact, four collagen type II patients showed a complete resolution of the disease . . .”
  − “We see that oral ingestion of collagen type II may well prove to be the most effective natural means of arthritis management regardless of the form of the disease.”
  − “. . . this is precisely why it works in osteoarthritis . . . collagen type II has such a high concentration of glucosamine and chondroitin . . .”
  − “In lieu [sic] of the fact that there are no side effects with collagen type II, this would seem to be the product of choice when suffering from any form of arthritic condition.”
  − “. . . collagen II components are truly chondro-protective agents because they . . . reprogram destructive chondrocytes and cytokines, reducing inflammation . . . protect the surface of the cartilage from oxidative damage . . . act as a powerful anti-inflammatory and pain modulator.”

• Under the heading “Collagen Type II [an ingredient in CellRenewPRO and CellRenewSTS] and Heart Disease”:

  − “Medicines such as aspirin and NSAIDS, as well as natural therapeutics such as fish liver oil or antiarthritic herbs, cannot compete with the overall biochemical power of collagen type II.”
  − “. . . collagen type II is 14.2 percent chondroitin sulfate A. . . . Chondroitin sulfate A (CSA) has a powerful antithrombogenic or anticoagulant affect, which, in essence, prevents blood clots and has been shown to reduce the incidence of stroke.”
  − “. . . CSA literally reduced the cholesterol and other lipids in the blood and actually ‘cleared’ cholesterol from the lining of arteries, including the aorta.”
  − “This indicates a 600 percent reduction in the incidence of fatal heart attacks simply by taking oral CSA on a daily basis . . .”
  − “Collagen type II has also found some support in the research for the amelioration of autoimmune disease caused by breast implant poisoning, as well as amelioration of Menier’s [sic] disease and progressive myopia.”

On the “The Village of Long Life” webpage (https://appliedhealth.com/cellrenew-collagen-type-ii/hyaluronic-acid-abc-news/), which hyperlinks to the online storefront where the CellRenewPRO and CellRenewSTS products can be purchased:

• “. . . hyaluronic acid [a component of the Hydrolyzed Collagen II ingredient in the CellRenewPRO and CellRenewSTS products] has been used for years in eye surgery as a shock absorber to protect the retina, and has been proven effective in lubricating arthritic joints.”

• “But HA has been shown to have wound-healing and tissue-reconstruction applications . . .”

On the “Collagen Type II for Arthritis Pain Relief” blog post (https://appliedhealth.com/collagen-type-ii-for-arthritis-pain-relief/):

• “Collagen Type II [an ingredient in the CellRenewPRO and CellRenewSTS products] for Arthritis Pain Relief”

• “Does Collagen Type II relieve osteoarthritis? Research says, yes.”

• “Collagen type II (CTII) is an effective source for alleviating joint stiffness and increasing mobility. Several studies have found CTII reduces joint pain in rheumatoid arthritis, but a new study . . . found that it is also an effective treatment for osteoarthritis.”

• “Researchers recruited 52 subjects with osteoarthritis in the knees to take CTII or a glucosamine/chondroitin combination for 90 days. . . . Overall, CTII reduced joint pain by 40%.”

• “How does collagen type II alleviate joint pain? CTII is the primary form of collagen naturally found in joint cartilage. The body needs CTII to rebuild connective tissue. Supplementing with a superior form of collagen can help reduce inflammation and the breakdown of collagen in the body. For the best absorption, choose a hydrolyzed collagen type II to restore joint health.”

Your products are not generally recognized as safe and effective for the above referenced uses and, therefore, the products are “new drugs” under section 201(p) of the Act [21 U.S.C. § 321(p)]. With certain exceptions not applicable here, new drugs may not be legally introduced or delivered for introduction into interstate commerce without prior approval from FDA, as described in sections 301(d) and 505(a) of the Act [21 U.S.C. §§ 331(d), 355(a)]. FDA approves a new drug on the basis of scientific data and information demonstrating that the drug is safe and effective.

A drug is misbranded under section 502(f)(1) of the Act [21 U.S.C. § 352(f)(1)] if the drug fails to bear adequate directions for its intended use(s). “Adequate directions for use” means directions under which a layperson can use a drug safely and for the purposes for which it is intended (21 CFR 201.5). Prescription drugs, as defined in section 503(b)(1)(A) of the Act [21 U.S.C. § 353(b)(1)(A)], can only be used safely at the direction, and under the supervision, of a licensed practitioner.

Your Applied Health Solutions brand products B Complex, Daily Detox, CellRenewPRO, CellRenewSTS, and the NutriBiotic brand products Grapefruit Seed Extract CapsulesPlus and Grapefruit Seed Extract Liquid Concentrate are intended for treatment of one or more diseases that are not amenable to self-diagnosis or treatment without the supervision of a licensed practitioner. Therefore, it is impossible to write adequate directions for a layperson to use your products safely for their intended purposes. Accordingly, the B Complex, Daily Detox, CellRenewPRO, CellRenewSTS, Grapefruit Seed Extract CapsulesPlus, and Grapefruit Seed Extract Liquid Concentrate products fail to bear adequate directions for their intended use and, therefore, the products are misbranded under section 502(f)(1) of the Act [21 U.S.C. § 352(f)(1)]. The introduction or delivery for introduction into interstate commerce of these misbranded drugs violates section 301(a) of the Act [21 U.S.C. § 331(a)].

This letter is not intended to be an all-inclusive statement of violations that may exist in connection with your products. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations.

This letter notifies you of our concerns and provides you an opportunity to address them. Failure to adequately address this matter may result in legal action including, without limitation, seizure and injunction.

Please notify FDA in writing, within 15 working days of receipt of this letter, of the specific steps you have taken to address any violations. Include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. If you cannot complete corrective actions within 15 working days, state the reason for the delay and the time within which you will do so. If you believe that your products are not in violation of the Act, include your reasoning and any supporting information for our consideration.

Your written response should be sent to the following address: 6th Ave and Kipling St, DFC Bldg. 20, PO Box 25087, Denver, Colorado, 80225-0087, to the attention of Compliance Officer Carrie Jolly or by email to carrie.jolly@fda.hhs.gov. If you need additional information or have questions concerning any products distributed through your website, please contact CO Jolly at carrie.jolly@fda.hhs.gov or (303) 236-9656.

Sincerely,
/S/

E. Mark Harris
Denver District Director & Program Division Director
Office of Human and Animal Food Operations −
Division IV West