Efficacy of Standardized Celery Seed Extract in Patients with Chronic Painful  Inflammatory Conditions : A Clinical Study

 

Abstract

Osteoarthritis (OA) and rheumatoid arthritis (RA) are chronic painful conditions having detrimental effect on a patients’ quality of life. The pain in these chronic conditions is usually managed using non-steroidal anti-inflammatory drugs (NSAIDs) as per recommendations of clinical guidelines. However, NSAIDs are associated with cardiovascular, hepatic, renal and gastrointestinal risks.

Extracts from celery seeds are known to possess anti-inflammatory and analgesic properties. Hence, a tablet containing 250 mg of standardized celery seed extract was formulated and its efficacy and safety was evaluated in an open-label study involving adult patients (n=65, age=18-65 years) with chronic inflammatory conditions such as osteoarthritis and rheumatoid arthritis. The patients received 250 mg tablet containing standardized celery seed extract, twice daily for 8 weeks. The endpoint of the study was reduction in symptoms of the inflammatory conditions at the end of 8 weeks, measured by visual analogue scale (0: no distress; 10: unbearable distress). The symptoms which were evaluated included swelling (except hip joint); grinding, cracking or any other type of noise on moving knees; restriction of the movement; severity of joint stiffness after waking up in the morning; severity of joints after sitting, lying or resting later in the day; pain during movements and difficulties faced while doing daily activities.

Excellent efficacy in reduction of joint swelling was observed in 45% of the patients; 46% of the patients showed good efficacy in reducing grinding/cracking knees on movement; 42% showed excellent efficacy in reducing restriction of movements; 49% showed good efficacy in reducing morning stiffness and pain during movements and 57% showed good efficacy in reducing difficulty in doing daily chores. No adverse effects were seen in 61.5% of the patients. The administration of standardized celery seed extract tablets 250 mg twice daily for 8 weeks were effective and well tolerated in OA and RA patients.

 

Introduction :

Osteoarthritis (OA) and rheumatoid arthritis (RA) are chronic painful conditions affecting an individual’s quality of life.[1] RA is an inflammatory disease of synovial joints characterized by pain, which adversely affects functional ability and psychosocial outcomes. RA pain may be attributed to joint inflammation, which is intensified by central sensitization and structural joint damage.[2] Globally, OA is the most common form of arthritis and one of the most frequent causes of musculoskeletal pain.[3] The pain due to OA is caused by multiple factors within and outside the joint, driven by nociceptive and neuropathic mechanisms, along with abnormal excitation in the pain pathways of the peripheral and central nervous system (CNS). Inflammation in the joint initiates a cascade of events leading to peripheral sensitization, increased sensitivity of nociceptive primary afferent neurons, and hyper-excitability of the nociceptive neurons in the CNS.[4]

Non-steroidal anti-inflammatory drugs (NSAIDs) are effective in relieving pain, swelling, and arthritic stiffness and other rheumatic diseases.[5] They are recommended by clinical guidelines for managing pain and inflammation in OA (first-line treatment) as well as RA. However, NSAIDs are associated with cardiovascular, renal, hepatic and gastrointestinal adverse effects.[1,5]

Celery seed extract is documented to be effective and safe. The extract has anti-inflammatory, analgesic and gastro-protective properties.[6] Celery preparations have been used extensively since ancient times as natural therapies for managing acute and chronic painful or inflammatory conditions.[7] Celery plant (Apium graveolens) is an indigenous plant from family Apiaceae. According to Ayurveda, the plant has a broad spectrum use as an aphrodisiac, anthelmintic, antispasmodic, carminative, diuretic, emmenagogue, laxative, sedative, stimulant, and toxin.[8]

A single arm open-label, multi-centric study involving 50 doctors across India was carried out to investigate the efficacy of standardized celery seed extract tablets (Celery seed extract) for the treatment of chronic painful inflammatory conditions such as osteoarthritis and rheumatoid arthritis in adults.

 

Methodology:

SUBJECTS :

Sixty-five adult patients (n=65), ages 18 to 65 years with rheumatoid arthritis and osteoarthritis were included in the study. Patients who were pregnant or nursing, those with compromised renal function, those who are planning surgery, or having history of allergic reaction or poor tolerability to celery seed extract were excluded from the study.

 

TREATMENT :

Patients received treatment with one 250 mg tablet of Celery seed extract after meals, twice daily for 8 weeks.

 

CLINICAL  ASSESSMENT :

The efficacy of Celery seed extract was clinically assessed by self-evaluation by the patients and clinical examination by the physician. The gradation of pain was determined using a 0-10 Visual Analog Scale (VAS), with 0 being no distress and 10 as unbearable distress. The severity of the symptoms was graded based on the VAS scores as 0 = absent; 1-3 = mild; 4-6 = moderate; 7-10 = severe. Following symptoms were evaluated before the initiation of treatment, after 4 and 8 weeks of the treatment.

  • Swelling (except hip joint)
  • Grinding, cracking or any other type of noise on moving knees.
  • Restriction of movement
  • Severity of joint stiffness after waking up in the morning
  • Severity of joint pain after sitting, lying or resting later in the day
  • Pain during movement
  • Difficulties faced while doing daily activities

 

Reduction in the OA/RA symptoms such as joint pain, stiffness, inflammation and difficulty in joint movements were the end-points of the study.

 

Results:

PATIENT CHARACTERISTICS :

Out of 65 patients, 45% of patients were male (n=29) and 55% were female (n=36); 82% of patients were diagnosed with OA (n=53); 3% with RA (n=2), and 15% with joint pain (n=10). The presenting clinical symptoms of participants are summarized in Table 1.

TC- Oct 2016 - 067 - Presenting clinical symptoms

SYMPTOMATIC  IMPROVEMENT :

The symptomatic improvement of the chronic conditions as rated by the physicians (Figure 1) and patients (Figures 2).

TC- Oct 2016 - 066 - Symptomatic improvement

TOLERABILITY :

No adverse effects were reported during the course of the treatment by 61.5% of the patients.

TC- Oct 2016 - 068 - Symptomatic improvement

Discussion :

This open-label study showed the efficacy of celery extract in reducing symptoms usually experienced in chronic inflammatory conditions such as RA and OA.

NSAIDs are universally used in rheumatology as anti-inflammatory and analgesic agents. NSAIDs prevent prostaglandin production by inhibiting the activity of the enzyme cyclooxygenase (COX).[5] They are superior to paracetamol in terms of efficacy. Systematic reviews have reported superiority of NSAIDs for rest pain and overall pain.[9] However, the use of NSAIDs is associated with a risk of adverse events, including cardiovascular (heart failure, myocardial infarction, stroke, cardiovascular death), renal (sodium retention, weight gain and edema, hypertension, type IV renal tubular acidosis and hyperkalemia, acute renal failure, papillary necrosis, acute interstitial nephritis, accelerated chronic kidney disease), hepatic (elevated transaminases), gastrointestinal (dyspepsia, esophagitis, gastroduodenal ulcers, ulcer complications (bleeding, perforation obstruction), small bowel erosions, and strictures colitis), asthmatic, allergic, nervous and hematologic problems.[1,5] These risks are seen with both, non-selective and COX-2- selective NSAIDs, even though COX-2 inhibitors exhibit better GI safety profile.[9]

An extract of the seed from celery, Apium graviolens, has been found to possess anti-inflammatory activity, gastro-protective activity, and anti-Helicobacter pylori activity.[10] Celery preparations have been used extensively for managing acute and chronic painful or inflammatory conditions. Celery Seed Extract (CSE) has been found to possess similar efficacy as aspirin, ibuprofen, and  naproxen in suppressing arthritis in a model of polyarthritis and also been proven as an analgesic in two experimental models. CSE, apart from its analgesic and inflammatory activity, has also been shown to protect against and/or reduce gastric irritation caused by NSAIDs, and act synergistically with them in reducing inflammation.[7] Toxicological investigations of alcoholic extract of celery seeds found no toxicologically significant sub-chronic effects in experimental animals.[10]

Celery seed extract inhibits COX 1 and 2 and thus prevents prostaglandin synthesis. Pre-clinical studies have shown similar efficacy of celery seed extract and ibuprofen in reducing inflammation. The extract has also been proven to possess better gastro-protective action than omeprazole. A 12-week study was carried out in 15 patients with either OA, osteoporosis or gout. The patients received 34 mg of celery extract twice daily. The study found that after 3 weeks of the treatment, the average reduction in pain scores was 68%, with 100% pain relief in some patients. Maximum benefit was observed in patients who continued treatment for 6 weeks. Based on the results of this study, another study was conducted with larger patients (n=70) receiving higher dose of the extract (75 mg). The study reported statistically and clinically significant reductions in pain scores, mobility and quality of life. Another clinical study on 10 patients with OA found 75% relief in pain in patients receiving the celery seed extract as compared to placebo. Also, there was no observed toxicity or side effects.[6]

A larger study was conducted with 112 patients (20- >61 years) over a period of 9 months. The study found that 61% of patients showed excellent relief from symptoms, while 27% showed good relief. The study demonstrated that patients dependent on steroids were steroid-free within 3 months; analgesics and hypnotics were discontinued; there was no change in rheumatoid factor (RF) positive patients, but signs of clinical improvement were seen.[6]

As observed in this post surveillance study, the standardized celery seed extract effectively reduced symptoms of chronic pain associated with inflammatory conditions i.e., RA and OA and was well tolerated.

 

Conclusion:

The administration of standardized celery seed extract tablets 250 mg twice daily for 8 weeks was effective and well tolerated in patients with chronic inflammatory painful conditions, such as, rheumatoid arthritis and osteoarthritis.

 

Study Contributors :

Dr. Premesh Sarkar, Kolkata; Dr. Somenath Ghathak, Kolkata; Dr. Rajeev Kumar Roy, Patna; Dr. Sanjay Anand, Patna; Dr. Pankaj Singhania, Purulia; Dr. Tarunjit Dutta Roy, Krishnanagar; Dr. Sanjeev Marwaha, Varanasi; Dr. Gurdesh Mehta, Tarntaran, Punjab; Dr. Nitish Kabra, Ajmer; Dr. Siddaiah K., Bengaluru; Dr. T.R Sudheendra, Bengaluru; Dr. Sandeep Reddy, Adilabad; Dr. CS Rai, Ratlam; Dr. Harish Afzulpurkar, Mumbai.

 

References :

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  4. Salaffi F, Ciapetti A and Carotti M. The sources of pain in osteoarthritis: A pathophysiological review. Reumatismo.2014 Jun 6; 66(1):57-71.5  Cro
  5. fford Li. Useof NSAIDs in treating patients with arthritis. Arthritis Res Ther.2013;15 Suppl 3:S2.
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  9. Yu SP and Hunter DJ. Managing osteoarthritis. Aust Prescr 2015; 38:115-9.
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