Capsicum

Ransom Naturals' Pharmaceutical-Grade Capsicum with DMF/ASMF On the beach Kafka, If I Had Not Written, 1Q84 and In the Footsteps of the Wild Sheep like books of famous Japanese author Haruki Murakami says of American music group The Red Hot Chili Peppers "They teach us how to age" and adds "You said the mind is like wind butmaybe we are like wind, knowing nothing, only blowing. Never aging, never dying." Through these words, the author describes how the band, despite reducing their noise/tempo over 40 years of musical life, puts their listeners into a state of spirit that always "feels/makes feel".

"Pungency" Is Not a Sensation to Be Unfelt

Red Hot Chili Pepper—Capsicum Annuum in Latin—the familiar red chili pepper in common terms, has been used in numerous different dishes worldwide since ancient times, that is, in our kitchens. The small red fruit commonly used to emphasize the pepper owes its pungent sharpness to Capsaicin, a chemical isolated by chemists more than a century ago that constitutes approximately 12% of hot pepper. Capsaicin is the most dominant and naturally occurring alkamide found in Capsicum fruits. Since its discovery in the 19th century, the therapeutic roles of Capsaicin have been well characterized. The potential applications of Capsaicin range from food flavours to therapeutics. Indeed, Capsaicin and a few of its analogues have been included in clinical research covered by more than one thousand patents. Pharmacological activities of Capsaicin such as Analgesic, Anti-obesity, Anti-allergic, Anti-inflammatory, Anti-apoptotic, Anti-cancer, Anti-oxidant and Neuro-protective functions have been discovered. Moreover, emerging data demonstrate its clinical significance in the treatment of Cardiovascular diseases, Metabolic syndromes and Gastro-protective effects. The scarcity of potent drugs for the treatment of such disorders has necessitated motivation for further research on the pharmacological aspects of Capsaicin. With seafaring expeditions to the New World and Europe's conquest or, to some, discovery of America, the transfer of foods between the known and unknown worlds introduced Capsicum to the known world. Consumption of hot pepper by inhabitants of the Tehuacán Valley (Mexico) dates back 8000 years (7000-6000 BC). Archaeologists, estimating that hot pepper cultivation began around 5200-3400 BC, classified it as one of the oldest domesticated plants. After the discovery of the New World, this small fruit was introduced to Europe and its cultivation gradually spread to other parts of the world. Today the red pepper is considered one of the global foods found in almost every country and adopted as an essential component in the kitchens of different cultures. Due to its worldwide consumption, it is known under various names such as aji, cayenne, red pepper, hot pepper, jalapeno and tabasco. Since 7000 BC, Capsicum has had a long and winding history in the kitchen and traditional medicine. Capsaicin, in addition to its use in the kitchen, has been used in a wide variety of other applications including repelling insects, defense products (pepper spray), protecting plants from elephant herds (hot manure bombs), driving away squirrels (Capsaicin-flavored bird seed) and deterring mischievous children. In traditional medicine, Capsicum was consumed by people in tropical countries to cope with hot weather by regulating heat loss through Capsaicin-induced skin vasodilation (vessel expansion) and perspiration. Other folk remedies include treatments for cough, sore throat, tonsil inflammation, gastric ulcer, back pain, cholera, gout, edema, rheumatism, cramps, diarrhea, indigestion, toothache, appetite stimulation and restoration of hair growth. Despite its widespread use, the biological aspects of Capsaicin were not well understood until the discovery of its dual actions on sensory neurons: acute, but transient stimulation, observed as a long-term state of tolerance generally known as desensitization. The curative effects of Capsaicin began to emerge in the 19th century. Western people initially used Capsaicin to treat itching or skin inflammation. Buchheim (1873) and Hogyes (1878) were the first to report burning symptoms produced by contact of Capsicol (partially purified Capsaicin) with mucous membranes and increased gastric juice secretion, thus demonstrating its first pharmacological effects. Pharmacological Properties of Capsaicin: Ointments/creams containing Capsaicin have long been used to relieve chronic neuropathic pain disorders. Topical application of Capsaicin has been found to be potent in the treatment of Skin Disorders, Herpes Zoster, Muscle Tension, Arthritis-related disorders, Diabetic Neuropathy and other pain disorders. The EU has supported Capsaicin applications for pain conditions associated with Post-Herpetic Neuralgia (PHN), Peripheral Neuropathic Pain (PNP) and HIV-related Distal Sensory Polyneuropathy (HIV-DSP) for Qutenza. In the United States, the FDA has approved its use only for PHN. The studies I will discuss describe Capsaicin as an exciting pharmacological agent. Its application in different clinical conditions but for similar purposes is still being investigated today. In addition to its Pleiotropic, Pharmacological and Physiological roles, Capsaicin has been examined in the food sector as a potent natural inhibitor of Pathogenic Microorganisms for antimicrobial and antiviral activities. The bulk of Capsaicin pharmacology focuses on treating various painful conditions. Additionally, beneficial effects and roles of Capsaicin have been observed in the treatment of Dermatological, Gastrointestinal and Cardiovascular problems, various cancers, obesity and many other pathologies. Capsaicin and Neuropathic Pain Capsaicin is believed to block pain transmission to the spinal cord. It is effective in treating pain caused by Herpes Zoster and Neuralgia. It provides analgesic effect. Neuropathic pain is defined as pain characterized by tonic, unrelenting pain with sensory-related symptoms such as burning, numbness or hypersensitivity, arising from lesions or disorders affecting Peripheral or Central Sensory Nerves. Pharmacological interest in Capsaicin for neuropathic pain has resulted in "long-term pain reduction" efficacy not only through the identification of the Capsaicin receptor and its location on peripheral nerves or its role in pain relief, but also through its capability to produce degeneration in Nociceptor Fibers at repeated doses in general. Capsaicin-based topical formulations have been examined using three different concentrations (0.025% and 0.075%, considered "low dose" and 8%, "high dose") to determine the most effective dose with fewer side effects. Since the early 1980s, formulations containing low-concentration Capsaicin, namely <1%, have been sold over-the-counter (OTC) in many countries for the treatment of neuropathic and musculoskeletal pain. Several reports have demonstrated the safety and efficacy of using 8% Capsaicin patches in the treatment of neuropathic pain resulting from PHN, post-traumatic neuropathy, HIV-DSP, post-operative neuralgia and mixed pain syndromes. Capsaicin and Musculoskeletal-Origin Pain Various conditions can cause musculoskeletal pain, including arthritic disorders (OsteoArthritis OA & Rheumatoid Arthritis RA), Fibromyalgia, repetitive strain injury, back pain and other chronic muscle pain. Most clinical therapies for arthritis pain are directed orally, but various topical formulations including NSAIDs (Nonsteroidal anti-inflammatory drugs) and Capsaicin are also used. Low-dose topical Capsaicin (0.025% or 0.075%) is commonly used to treat arthritis pain. In a double-blind and randomized 4-week study, 70 patients with OA and 31 patients with RA applied Capsaicin 0.025% cream or placebo to painful knees. Most patients continued concurrent arthritis medications and reported a 57% reduction in RA pain and 33% reduction in OA pain after 4 weeks of Capsaicin treatment.

Capsaicin and Migraine Pain

Chronic migraine, from frequent flare-ups to persistent headache, is presented with a progressive increase in attack frequency. Previous studies provided Intranasal Capsaicin as a novel therapeutic option for the management of headaches presenting in this manner. Two subsequent studies demonstrated the efficacy of Intranasal Civamide for the management of migraine and episodic headache. Patients treated with Capsaicin showed improvement in their migraines. Another study demonstrated the efficacy of Capsaicin gel (0.1%) in reducing migraine in patients suffering from arterial pain at the onset of migraine. In short, acute treatment of migraine headache using Intranasal Civamide and Capsaicin gel has been observed. Some of the OTC products available in the global market are marketed under the names Capzasin P, Zostrix, Capzasin-HP, Axsain, No Pain-HP, Pain Doctor, Pain-X, Rid-A-Pain, Salonpas Hot, Trixaicin and Menthac. Capsaicin and Its Effects on the Upper Respiratory Tract Red pepper tincture warms your throat and relieves any discomfort, it also helps loosen mucus and clear your respiratory passages for easier breathing. Cough, cold and throat preparations contain them at low levels. Capsaicin and Anti-Cancer Effects Red pepper reduces cancer risk because it contains anti-inflammatory nutrients and antioxidants. Lycopene, a carotenoid found in bell pepper, is also effective in reducing the risk of Cervical, Prostate, Pancreatic and Bladder Cancer. Enzymes in red pepper also help prevent esophageal and gastric cancer. Capsaicin has been reported to reduce cancer cell growth, cause cell cycle arrest and trigger programmed cell death in cell lines including Adenocarcinoma, Breast Cancer, Colon Cancer, Cutaneous Cell Carcinoma, Esophageal Carcinoma, Gastric Cancer, Glioma, Hepatocellular Carcinoma, Leukaemia, including Multiple Myeloma, Nasopharyngeal Carcinoma, Non-Small Cell Lung Cancer, Pancreatic Cancer, Prostate Cancer, Tongue Cancer. It has also been shown to exhibit in vivo anticancer activity by reducing the progression of several tumors in mice. Due to these roles, Capsaicin is considered a novel cancer therapy candidate. Capsaicin's Genotoxic and Proapoptotic activities have been reported to be highly limited with cancer cells, whereas they do not induce cell cytotoxicity in normal cells. The antitumour properties of Capsaicin in various cancers and the underlying mechanisms have been documented in numerous other clinical studies. Treatment with a combination of Capsaicin and 3,3'-diindolylmethane (DIM) resulted in synergistic induction of apoptotic cell death and inhibition of cell proliferation in multiple colorectal cancer cell lines; studies using both in vivo and in vitro analysis have shown that Capsaicin has cytotoxic and antitumour properties in Pancreatic Cancer cells. Studies have also shown that chronic oral application of Capsaicin is safe, well tolerated and effective in reducing the metastatic burden of Prostate Cancer.  

Capsaicin and Anti-Obesity Effects

Due to modern lifestyle, an increasing number of people in both developed and developing countries suffer from obesity. Obesity is a chronic disease in which a person gains body fat to the extent that it may have a harmful effect on their health. A person is considered obese if their body weight is 20% more than normal. Obesity is a harbinger of various health problems such as Cardiovascular Disease, Type II Diabetes, certain types of cancer and Obstructive Sleep Apnea. One of the most promising areas of Capsaicin research is its potential to combat obesity. In the past decade, many laboratory and clinical studies have reported the therapeutic effect of Capsaicin as an anti-obesity drug. Studies suggest that both Capsaicinoids and Capsinoids can play a strong role in weight management alongside exercise and diet measures and that Capsaisinoids in combination with other bioactive compounds can have a synergistic effect on weight loss. Upon consumption of a high-fat diet, oral Capsaicin consumption over 120 days has been shown to reduce the number and size of fat cells, thereby preventing Adipogenesis (Fat Formation) and the development of Obesity. In a series of human studies, reduced food intake following red pepper consumption, Reduced Appetite and increased diet-dependent Thermogenesis (Metabolic Rate) were reported to result primarily from the sensory or gastrointestinal effects of Capsaicin. Capsaicin and Its Effects on the Gastrointestinal System Several researchers have conducted comprehensive studies with Capsaicin in the field of gastroenterology. Gastrointestinal effects of Capsaicin show both beneficial and harmful results depending on the doses applied. Protective effects of Capsaicin on gastric mucosa have been documented in both animal and human studies. In red pepper consumption, Capsaicin-derived gastroprotective effects against aspirin-induced gastroduodenal mucosal damage have been reported in humans. Furthermore, a preliminary report showed that long-term red pepper intake in Irritable Bowel Syndrome (IBS) patients with enteric-coated tablets was significantly more effective in reducing the intensity of abdominal pain and bloating. Capsaicin and Its Effects on Cardiovascular Health Studies have shown beneficial effects of dietary Capsaicin on Atherosclerosis (Vessel Hardening), Hypertension, Cardiac hypertrophy (Heart Muscle Thickening) and Stroke risk. Daily pepper intake for 4 weeks was reported to increase the resistance of serum lipoproteins to oxidation in adult men and women due to the antioxidant properties of Capsaicinoids. The antiplatelet aggregation effects of Capsaicin on platelets through TRPV1 (Capsaicin Receptor) dependent or independent mechanisms have also been investigated. Capsaicin has been shown to penetrate the plasma membrane of platelets and alter membrane fluidity. LDL oxidation has led to the development and progression of Atherosclerosis. Studies showing that Capsaicin increased the resistance of LDL to oxidation by delaying the initiation of oxidation and/or slowing the rate of oxidation also indicate that Capsaicin is important in preventing cardiovascular disorders including Atherosclerosis and Coronary Heart Disease. In spontaneous hypertensive rats prone to stroke, dietary Capsaicin was found to trigger the activation and expression of eNOS and thus cause a delay in stroke onset. To summarize, the role of dietary and transdermal Capsaicin in the treatment of Cardiovascular diseases has been outlined. Capsaicin and Its Effects on Dermatological Diseases Topical Capsaicin has been used in the treatment of various dermatological disorders including Alopecia Areata (Alopecia Areata), Apocrine Chromhidrosis (Coloured Sweating), Aquagenic Pruritus (Itching), Brachioradial Pruritus (BRP—Intense Itching), Hemodialysis-related Pruritus, Lichen Simplex Chronicus (Neurodermatitis), LipoDermatoSclerosis (LDS), Meralgia and Motalgia Paresthetica, Postherpetic Neuralgia (PHN) and Psoriasis. In various studies, topical Capsaicin demonstrated significant antipruritic effects in patients receiving hemodialysis, with the antipruritic role of Capsaicin showing a possible link between TRPV1 and histamine-related itching definitively established. Ransom Naturals' Pharmaceutical-Grade Capsicum Now, if we are to address Capsicum, or rather Red Pepper, transformed from its natural state into an industrial raw material with high active component values, bringing these unique benefits to large-scale global use, we must tell you the story of a well-established manufacturer. Shortly after completing his apprenticeship in pharmacy in 1846, a chemist named William Ransom established the first volatile oil extraction facility in the Hitchin district of London. The operation quickly gained an international reputation due to its commitment to quality. William Ransom, with the great commercial success he achieved in a short time, also employed many local people to work in his laboratory or to gather raw materials from the wild, thereby contributing significantly to Hitchin's economy. The company's warehouses were filled with plants from all over the world. Francis Ransom, William's son, who was himself a respected pharmacist and published scientific articles on plants, joined his father's business in 1913 and oversaw the company's research and development work. Subsequently, the company's name was reorganized as William Ransom &Son. After William and Francis passed away, Richard, Francis's son who was a botanist, took over the company with great interest in developing medical products from plants. As a highly respected employer, he successfully ran the company through the difficult times of World War II. In 1981, it moved to a new and larger facility, both producing raw materials for the Pharmaceutical Industry and launching its own finished products to the retail market. In the early 2000s, William Ransom &Son moved to its current address on Burymead Road. In 2007, the Company received GMP (Good Manufacturing Practice) accreditation—a quality standard—and became the first UK-based Herbal Medicine Company to do so. Acquired by OBG Group in 2012, the company became known as Liverpool-based Ransom Naturals Limited (RNL). Throughout its existence, Ransom has successfully combined innovative approaches to new product development with traditional methods, doing so by remaining true to its love of nature and adapting and benefiting from the latest scientific techniques to continue meeting the constantly changing needs of markets and customers. Proud of its heritage, the forward-looking company currently serves a wide variety of international markets. Ransom Naturals Ltd is one of the few European Capsicum Extract manufacturers producing to cGMP requirements. Meeting the growing requirements of GACP (Good Agricultural and Collection Practice), sourcing Red Pepper through an approved supply chain, it transforms it into standardized liquid raw materials with DMF/ASMF certification of different contents in its cGMP facility in the United Kingdom. The products contain 6 main Capsaicinoids defined in Current Pharmacopoeia Monographs: • Capsaicin, • Dihydrocapsaicin, • Nordihydrocapsaicin, • Decanylvanillinamide, • Homocapsaicin, • Nonivamide. Synthetically derived Nonivamide has historically been added to Capsicum extracts as a way to increase the declared content of Capsaicinoids and therefore Nonivamide content is controlled in all extract specifications.

In summary, Ransom Naturals;

• Is a European manufacturer of Capsicum Extract, Oleoresin and Tincture. • Produces many Herbal Extracts including Capsicum according to Pharmacopoeia monographs or customer-specific requirements. • Provides Formulation Development support for Products addressing the Pharmaceutical, Nutra/OTC, Cosmetic and Food sectors. • Provides substantial support to customers in the Product Licensing process. Ransom this year has planned growth with a GBP 1.5 million investment in laboratory, research and development and production capacity increases. While having established a solid position in the pharmaceutical sector, alongside Capsicum, it aims to enrich its current portfolio with various other Herbal Extracts designed with Drug Substance and API precision in its GMP-certified facility. As the Pharmaceutical &Nutra Division of Barentz, we represent the portfolio of our valued manufacturer Ransom Naturals with great interest, pleasure and admiration. References: https://www.vox.com/2015/1/21/7862005/harukimurakami-rhcp https://en.wikipedia.org/wiki/Capsicum_annuum https://www.sciencedirect.com/topics/pharmacologytoxicology-and-pharmaceutical-science/capsicumannuum https://www.sciencedirect.com/science/article/abs/ pii/S0065774320300063 https://www.sciencedirect.com/science/article/pii/ B978044453717101458X https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC6272969/ https://www.ttb.org.tr/sted/sted0703/kronik.pdf https://www.thecomet.net/news/hitchin-sransom-naturals-still-leads-the-way-inpharmaceutical-5365902 https://ransomnaturals.com/product/capsicum/ https://ransomnaturals.com/wp-content/uploads/2020/10/RNL-Pharmaceutical-Product-List.pd Burak Kamalı Business Development Manager Barentz Food and Chemical