review article - nutraceuticals and functional foods in the management of arthritis

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Daniel A. Nyaaba Page 1 REVIEW ARTICLE NUTRACEUTICALS AND FUNCTIONAL FOODS IN THE MANAGEMENT OF ARTHRITIS Author: Daniel Ayine Nyaaba Kwame Nkrumah University of Science and Technology Department Of Biochemistry and Biotechnology Correspondence should be addressed to [email protected] ABSTRACT Arthritis refers to different joint disease conditions. Arthritis is very prevalent. It is one of the most common chronic diseases and a main cause of disability and work limitations. Osteoarthritis (OA) and Rheumatoid arthritis (RA) are the most widespread and disabling form of joint chronic illness affecting mostly older people. There is no cure for arthritis and palliative care is used to alleviate the pain and discomfort caused by these conditions. Non Steroidal Anti-Inflammatory Drugs (NSAIDs) are mostly used by persons with arthritis to relief pain and discomfort associated with the disease. Most of these drugs however are associated with detrimental and undesirable side effects. This suggests the need for an alternative and reliable form of treatment; although the lack of cure reinforces the need for prevention. Some nutraceuticals and functional foods have proven effective for managing and/or preventing arthritic complications. The common ones include Glucosamine and/or Chondroitin sulphate, Aflapin and 5-Loxin, S-Adenosyl Methionine (SAMe), Probiotics, Vitamins and Mineral supplements, some Plant and Animal Extracts, Methylsulfonylmethane

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Page 1: Review article - Nutraceuticals and Functional foods in the management of arthritis

Daniel A. Nyaaba Page 1

REVIEW ARTICLE

NUTRACEUTICALS AND FUNCTIONAL FOODS IN THE

MANAGEMENT OF ARTHRITIS

Author: Daniel Ayine Nyaaba

Kwame Nkrumah University of Science and Technology

Department Of Biochemistry and Biotechnology

Correspondence should be addressed to [email protected]

ABSTRACT

Arthritis refers to different joint disease conditions. Arthritis is very prevalent. It is one of

the most common chronic diseases and a main cause of disability and work limitations.

Osteoarthritis (OA) and Rheumatoid arthritis (RA) are the most widespread and disabling

form of joint chronic illness affecting mostly older people. There is no cure for arthritis and

palliative care is used to alleviate the pain and discomfort caused by these conditions. Non

Steroidal Anti-Inflammatory Drugs (NSAIDs) are mostly used by persons with arthritis to

relief pain and discomfort associated with the disease. Most of these drugs however are

associated with detrimental and undesirable side effects. This suggests the need for an

alternative and reliable form of treatment; although the lack of cure reinforces the need for

prevention.

Some nutraceuticals and functional foods have proven effective for managing and/or

preventing arthritic complications. The common ones include Glucosamine and/or

Chondroitin sulphate, Aflapin and 5-Loxin, S-Adenosyl Methionine (SAMe), Probiotics,

Vitamins and Mineral supplements, some Plant and Animal Extracts, Methylsulfonylmethane

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Daniel A. Nyaaba Page 2

(MSM) among others. This paper is a review of the evidence supporting the use of

nutraceuticals and functional foods in the management of arthritis.

INTRODUCTION

Arthritis is a collective term for different disease conditions of joints. Arthritis results in the

inflammation of joints and consistent localized pain is typical of affected joints [1]. The pain

experienced in arthritis could be a result of inflammation at the affected joint, damage to the

joint by infection, daily wear and tear at the joint, fatigue or oxidative stress among others.

Arthritis is very prevalent. It is one of the most common chronic diseases and a main cause

of disability and work limitation in about 40% of people with arthritis in the United States

[2].Osteoarthritis (OA) and Rheumatoid arthritis (RA) are the most widespread forms of

arthritis [55, 23]. Other rare ones include psoriatic arthritis, septic arthritis, lupus and gout.

Osteoarthritis is the most prevailing form of arthritis and disabling form of joint chronic

illness affecting older people and nearly 27 million individuals in the United States alone [3]

This condition occurs with progressive damage of cartilage around joints resulting in their

malfunctioning, intense ache or deformity [4].This could be a result of trauma at the joint,

infection or ageing.

Rheumatoid arthritis (RA) differs from Osteoarthritis (OA) in that, it’s a systemic

autoimmune polyarticular synovitis engage major and minor joints resulting in pain, joint

destruction and reduced productivity in affected victims [5]. This means the body’s own

immune system attacks its tissues, and when this is directed to joints, it results in damaging

the joint lining and cartilage and subsequently arthritis develops.

There is no cure for arthritis and palliative care is used to alleviate the pain and discomfort

caused by these conditions. Currently, the recommended treatment protocol for persons with

arthritis includes both pharmacological treatments (such as Nonsteroidal Anti-Inflammatory

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Drugs (NSAIDs) or paracetamol among others) and nonpharmacological interventions, which

usually involves life style changes such as weight reduction and increase in physical activity

among others [4].

Most of the pharmacological treatments such as NSAIDs are predominantly linked with

several life threatening conditions such as renal failure, coronary heart disease and

gastrointestinal bleeding, with prolonged use or mega dosages especially in older persons [6].

Although they are associated with increased illnesses and deaths, they remain top among

prescribed drugs [7]. This suggests the need for an alternative and reliable form of treatment;

although the lack of cure reinforces the need for prevention. Although novel medications

with minimal side effects, such as (COX-2) inhibitors have been introduced, there is need for

better alternative treatments.

Fortunately, some nutraceuticals and functional foods have proven effective as an alternative

for managing arthritic conditions. Nutraceutical was derived for the words nutrition and

pharmacological and they include foods substances with medicinal potentials such as disease

prevention or treatment of illnesses [4]. Examples of nutraceuticals include isolated nutrients,

dietary supplements, genetically modified foods, herbal products and processed products such

as cereals, soups and beverages [1, 8].

Functional foods form an integral part of our routine diets; however, the potentials of

functional foods such as their health promoting effects, exceeds what food nutrients typically

provide [9]. Food can be modified and made functional either by enhancing its bioavailability

or removing its unhealthy components or adding ingredients that have health promoting

potentials [10] Public health professionals deem the treatment or preventive potentials of

nutraceuticals or functional foods a step forward in health promotion and a solution to some

acute and chronic diseases and in maintaining quality of life [1]. This paper is a review of the

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relevant evidence associated with the use of nutraceuticals or functional foods in the

prevention, management or treatment of arthritis.

THE ROLE OF FUNCTIONAL FOODS AND NUTRACEUTICALS IN ATHRITIS

1. Dietary Supplements

Dietary supplements are substances taken to compensate for nutrient deficits and have been

demonstrated in clinical trials to affect the aetiology of diseases. The aim using dietary

supplements is to ensure that, the body has adequate supply of essential nutrients to support

its growth and development, and to regulate physiological functions. Dietary supplements

that have proven effective in arthritis include substances such as glucosamine or chondroitin

sulphate, plant and animal extracts, vitamins and minerals supplements,

methylsulfonylmethane and phytochemicals among others [4, 11]. These serve specific

functions in the body such as weight reduction or relieving symptoms of the arthritis. This

section of the paper reviews the efficacy of some Dietary supplements in providing some

relief for complications of arthritis; particularly Osteoarthritis and Rheumatoid Arthritis.

Glucosamine and chondroitin sulphate

Glucosamine and/or Chondroitin sulphate supplements are claimed to be helpful to patients

with problems of Rheumatoid arthritis and/or Osteoarthritis in most clinical trials.

Glucosamine is a monosaccharide, which is naturally synthesized in the human body from

glucose [12]. Glucosamine acts as the core substrate for the synthesis of the constituents of

cartilage such as proteoglycans and glycosaminoglycans [12].

Chondroitin is a glycosaminoglycan found in cartilage and connective tissue [12]. The rational

for the use of Glucosamine and/or chondroitin is that they assist chondrocytes to make

proteoglycans, needed for cartilage production; hence helps prevent cartilage degradation that

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results in osteoarthritis [13]. Several researches have been done to elucidate the safety and

efficacy of glucosamine and/or chondroitin on bone health due to the increasing claims and

interest by consumers in recent times about these products.

The Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) in the United States

confirmed the safety of chondroitin and glucosamine as well as the anti – inflammatory drug,

Celecoxib in a 24 month study involving patients with osteoarthritis [14]. Also, the study

which assessed the safety and effectiveness of chondroitin and glucosamine sulphate alone,

their combination, as well as Celecoxib and a placebo, showed that only glucosamine and

Celecoxib were of benefit to people with osteoarthritis of the knee; as shown by the odds of

achieving 20% of Western Ontario and McMaster Universities Osteoarthritis Index

(WOMAC) being 1.16 and 1.21 for glucosamine and Celecoxib respectively [14].

In another study, Structum and Chrondrosulf, two Chondroitin sulphate from different

sources (avian and bovine) has been shown to be evenly efficient in alleviating pain and

improving function/activity in patients with symptomatic knee osteoarthritis over 6 months

period [15]. In the study, subjects were randomised to receive either Structum (avian,

1000mg/day) or Chondrosulf (bovine, 1200mg/day) and were observed for a period of 24

weeks. Statistically relevant improvements in pain and knee function were observed from the

sixth week of the study through to 24 weeks of the study. The finding of this study therefore

implies that both products could be recommended to persons with symptoms of osteoarthritis

of the knee.

Furthermore, a study in Mumbai, India compared the treatment potentials of glucosamine

sulphate and reparagen; a herbal mixture (polyherbal) on persons with OA [61]. 95 study

subjects involved in this pilot study were randomised to 1800mg/day or 1500mg/day of

reparagen or glucosamine respectively over an 8 week period. Within one, the treatment

demonstrated progressive and substantial improvements in Visual Analogue Scores (VAS)

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and WOMAC scores in both treatment cohorts. Joint ache/pains and stiffness among others

were greatly enhanced in both cohorts [61]

Again, the activity of a novel glucosamine based supplement mixed with Chondroitin

sulphate and micronutrient antioxidants (MSM, extract of guava leaves and Vitamin D) were

evaluated in Yokohama (Japan) [62]. This was a 16 week clinical trial involving 32 subjects

respectively allocated to 2300mg a day of examined supplement or the equivalent of a

placebo. Results from this study revealed inconclusive evidence on the action or treatment

effect on the study supplement. Although some notable greater improvements in some

outcome variables were detected in the treatment group compared to placebo, in all four

periods of routine assessments, the treatment effects were invariably different in both

treatment and placebo groups [62]. No incidence of detrimental/adverse reactions was

recorded in this study.

Finally, the treatment potential and safety of Aquamin was also evaluated with Glucosamine.

Aquamin is calcium and magnesium rich mineral supplement obtained from the red algae

Lithothamnion corallioides and has diverse trace minerals proven to be effective in pain and

stiffness relief after 12 weeks of use in individuals with osteoarthritis [16].

This observation was made in a preliminary study conducted on Aquamin in Minneapolis,

USA involving 70 subjects with modest to severe OA. Participants were randomised into four

groups and administered 1500 mg/d of Glucosamine sulphate; 2400 mg/d of Aquamin;

combined treatment composed of Glucosamine sulphate (1500 mg/d) plus Aquamin (2400

mg/d) and a Placebo. It was observed that, only the Aquamin group and the Glucosamine

group showed significant improvement in joint pain or stiffness, joint motility and walking

distance used as outcome assessment measures. A combination of Aquamin and

Glucosamine however, did not prove to be effective in solving complications of osteoarthritis

of the knee [16].

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Putting the evidence from all these clinical trials together, Glucosamine and/or Chondroitin

sulphate supplements or their combinations with other dietary substances suggest that they

have some level of activity in treating persons with arthritis. However, uses must exercise

caution as some combinations have proven ineffective or have minimal effect.

Aflapin and 5-Loxin

Semi-solid substances or gum resins derived from the herb Bosewellia Serrata; Aflapin and

5-Loxin, used as dietary supplement, has recently attracted attention as a cure for

inflammatory diseases and arthritic conditions [17]. Aflapin and 5-Loxin are both enriched

extracts of this ancient herb but are of different compositions in terms of their active

ingredients [17].

To evaluate the efficacy of these extracts, a clinical trial conducted in India on sixty subjects,

evaluated the efficient and safety of these extracts in the treatment of knee osteoarthritis.

Subjects were randomised into three groups and each received either 100mg of 5- Loxin or

100mg of Aflapin or a placebo for 90 days. In this study, both Aflapin and 5-Loxin proved

effective in relieving pain and improving on the joint function of patients with osteoarthritis

[17]. Aflapin however, was more effective compared to 5-Loxin; as patients who received

100mg/day Aflapin showed signs of improvement within seven days of administration.

Perhaps Aflapin was more efficient in hindering the activity of enzymes or the occurrence of

inflammation in patients with knee osteoarthritis. The research results also indicate that,

Aflapin and 5-Loxin are safe and can therefore serve as an alternative therapeutic dietary

supplement for arthritic persons.

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Another clinical trial assessed the efficacy of 5-Loxin alone using a similar study design.

Here, participants were given either 100mg/day or 250 mg/day of 5-Loxin or a placebo and it

was found that the treatment who received 250mg/day of 5-Loxin had the greatest

improvement in physical functions and pain scores within 7 days of usage [18]. Since the

study protocol used in this study was not much different from that involving both Aflapin and

5-Loxin in terms of sample size end duration it suggests that high dosage of 5- Loxin may be

more effective.

The efficacy of only Aflapin was also assessed in another clinical trial involving 60 eligible

participants for 30 days, where subjects were given 100mg Aflapin or a placebo daily [19].

Substantial improvement in physical function as well as pain reduction scores were observed

within five days of usage [19]. This suggests that Aflapin administered alone has a faster rate

of action compared with 5-Loxin and can therefore offer quicker relief to patients with knee

osteoarthritis. The impression I get from these trials hints that both Aflapin and 5-Loxin are

safe and efficient dietary supplements for the treatment of OA. Aflapin however is more

potent and acts faster compared to 5-Loxin and would be a better alternative.

S-Adenosyl methionine (SAMe)

S-Adenosyl methionine (SAMe) is non-essential nutrient used as dietary supplement. It

produced in the human body from methionine and Adenosine Triphosphate (ATP) and it

works primary as a methyl group donor in methyl transfer reactions [20]. SAMe is essential

for the synthesis of some neurotransmitters, glutathione, phospholipids and proteins and it has

proven effective for the treatment of arthritis, depression and liver disease [9].

The potency of SAMe for the treatment of OA was investigated in a clinical trial by

comparing it to Celecoxib (one of the new NSAIDs formulations; a cyclooxygenase-2

inhibitor) [20].

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The study was conducted in two phases of eight weeks per phase with one week washout

period between each phase. During the first, 1200mg SAMe (600mg twice daily) was

administered while 200mg Celecoxib (Celebrex 100mg twice daily) was given in the second

phase. It was found that SAMe was as effective as Celecoxib in alleviating pain and

enhancing joint function in persons with osteoarthritis of the knee. The impact of SAMe

however became evident after four weeks of treatment and it continued to increase

throughout the study compared to Celecoxib’s effect which remained stable [20].

SAMe can therefore serve as a suitable replacement for NSAIDs which associated with some

undesirable side effects. However, the challenge in the used of SAMe is that no effective or

safe dose of SAMe has been established and its mechanism of action is not clearly

comprehended. The combined effect of SAMe in combination with other treatment protocols

for osteoarthritis also needs further investigation.

Probiotics

Probiotics are substances that contain live microorganisms that could be beneficial to humans

and used in the treatment of several infectious and inflammatory disease conditions [21].

Probiotics obtained from Lactic Acid producing bacteria have been claimed to be beneficial

to persons with Rheumatoid Arthritis (RA) due to their ability to prevent inflammation and

modification of the immune system during treatment [22].

The impact of Probiotics obtained from Lactic Acid producing bacteria; Bacillus coagulans

on signs/symptoms and functional ability of patients with RA was assessed in a 60 day

clinical trial [23].

In addition to their routine anti-arthritic medications, 45 adult males and females with RA

were randomised to receive either Bacillus coagulans or a placebo daily for sixty days. Pain

evaluation scores improvement from base line was statistically significant in patients who

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received the probiotic (p=0.052). Subjects in probiotic intervention group generally showed

improvement in walking distance and ability to do routine activities among others and no

adverse effects were observed. Although, evidence from this study indicates that Bacillus

coagulans are effective for treating RA, a larger study with Bacillus coagulans alone is

required to elucidate the true efficacy of these Probiotics.

Also, autoimmune diseases such as RA may be caused by disruption of the gastrointestinal

microflora and impair in immune response to disease causing organisms [24].

The potential of probiotics to restore integrity of micro organisms in the gastrointestinal tract

has led to the investigation of the possible effect of probiotics in the treatment of RA.

A study was conducted to assess the effect of Lactobacillus rhamnosus and Lactobacillus

reuteri; probiotics capable of restoring gastrointestinal microflora and subsequent treatment

of RA. In line with findings regarding Bacillus coagulans there were improvements in

functional capacity of patients with RA compared to placebo in the three months of

investigations [25]. There was however no significant clinical effect of these Probiotics and

this can be attributed to the smaller sample size of 29 subjects; with only 15 and 14 receiving

the probiotic and placebo respectively.

Vitamins

Vitamins play several essential roles in the human. They function in boosting immunity

against diseases, helps in maintaining bone integrity, in energy production and as anti-

oxidants. Dietary Antioxidant micronutrients function to prevent oxidative damage in the

body by free radicals which are the cause of most inflammatory disease conditions [26].

Vitamin E, a fat soluble vitamin and a major antioxidant has therefore been associated with

reducing risk of developing Rheumatoid Arthritis (RA). Low serum concentration of vitamin

E; major antioxidant, may increase ones susceptibility to RA due to its protective role as an

antioxidant.

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Also a number of studies have observed relatively higher free radicals in the serum of persons

with RA [27] and within rheumatoid synovium [28]. On the contrary, other observational

case-control studies have opposed the preventive effect of Vitamin E on RA [29].

As part of the Women Health Study; a ten-year longitudinal study, no association between

prolonged use of vitamin E and the risk of RA was established. At the end of the study, 106

cases of RA occurred; 50 and 56 cases in vitamin E and placebo respectively and no

statistically significant correlation between them was observed; RR= 0.89 (95% C.I, 0.61-

1.31) [30]. The deduction drawn from this study was that, a reduction in risk of developing

RA was not related to the every other day 600 IU supplementations with Vitamin E among

women. The findings of other [31, 32] attributing RA to low levels of Vitamin E observed in

the plasma of both adult and young persons with prolonged RA was contradicted in this

study.

Furthermore, in a 6-month clinical trial, vitamin E proved ineffective in alleviating symptoms

of patients with knee OA [33]. This observation was made after seventy-seven patients with

OA were randomised to receive either vitamin E (500IU/day) or placebo (soybean tablets) in

the 6-month double blinded study. After assessing outcome measures such as knee pain or

stiffness and function, the results were unable to establish a significant benefit of vitamin E

over placebo on patients; as defined by the outcome measures [33]. Treatment effects of

Vitamin E (as in α-tocopherol) on both RA [34] and OA [35], have however been detected in

many clinical trials

No undesirable effects were observed in this; consistent with findings of other studies [36].

Detrimental effects were however noticed in other studies [37] over prolonged periods of use.

Evidence on the efficacy and safety of vitamin E and both RA and OA cannot be

substantiated at this moment. Hence further research is needed to establish a concrete

association between vitamin E supplementation and arthritis.

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The treatment potential of vitamin K in OA was also evaluated in 378 participants in a three

year clinical trial. This like vitamin E recorded no treatment effect of vitamin K on patients

with osteoarthritis of the hand over the three year period of study [63]. However, participants

who were vitamin K deficient experienced about a 47% treatment benefit over the period

[63].

Plant and Animal Extracts

1. Seaweed Extract (Maritech®)

Maritech is a concoction of 3 distinct varieties of brown algae extracts mixed with 3 other

micro nutrients; zinc, manganese and vitamin B6 [38].

The efficacy of this extract attributed to fucoidans (its active ingredient) is a subject of debate

with other theories for it [39] and others claiming the treatment effect are not linked to it [40].

The potential of this novel seaweed extract, in managing OA and its safety were investigated

in a pilot study to establish is effect. It alleviated symptoms of OA in patients over 12 weeks

of and the effect was dose dependent [38]. The observed effect can be comparable to

Methylsulfonylmethane (MSM) which also proved effective within 12 weeks of treatment

[41]. 12 participants with symptomatic OA were allocated either 100mg or 1000mg daily of

Maritech and followed for 12 weeks. An 18% reduction in mean primary outcome;

Comprehensive Arthritis Test (COAT) score was associated with 100mg/day and 52% for

1000mg/day of the nutrient extract. This effect is comparable to that associated with

conventional OA medications [42].

Although this study is limited by the absence of a place and the smaller sample size, it can be

deduced that since proved effective and no detrimental effects were observed, it is therefore

alternative supplement that may be used for managing OA.

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2. Botanical Extracts (NP 06-1)

A dietary supplement give the name NP 06-1, composed of two botanical extracts

(Phellodendron amurense bark and Citrus sinensis peel) has the potential to relief knee joint

pains or flexibility in persons with osteoarthritis of the knee [43].

This was an eight (8) week double-blinded, placebo-controlled study in Cameroon involving

80 participants randomized into four (4) groups. The purpose of the study was to compare the

effects of NP 06-1 to placebo on both standard/ideal weight and overweight subjects

diagnosed with primary osteoarthritis of the knee. Outcome measures such as Lequesne

Algofunctional Index (LAI) for joint pain, movement and biomarkers of inflammation were

assessed. They found that, NP 06-1 was effective in relieving joint pains associated

osteoarthritis as measured by the LAI score and anti-inflammatory effects confirmed using

the C-reactive protein (CRP). A reduction in weight was observed in both normal and

overweight participants in the treatment group. This reduction in weight could have

contributed to the effect observed.

Also, another nutritional supplement, AR7 Joint Complex; containing a variety of active

components including sternum collagen II and methylsulfonylmethane, may have short-term

effects in relieving pain in patients with osteoarthritis [44].

This was observed in a well designed study in Shanghai, China were 100 people aged over 50

years, with osteoarthritis were recruited into two groups; treatment (AR7 Joint Complex)

group and Control (placebo) group. Patients complaining of arthralgia and tenderness and

were part of the treatment group, had a significant relief in their symptoms (P< 0.01) and the

difference was significant in both treatment and control groups.

The constituencies of AR7 Joint Complex; sternum collagen type II, methylsulfonylmethane

(MSM), cetyl myristoleate (CMO), vitamin C, bromelain, turmeric, and lipase are suggested

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reasons for its activity [44]. For instance, collagen type II is a main constituent of cartilage in

joints and very central in joint function. The antioxidant property of vitamin C may also be

helpful in preventing oxidative damage at the joints that can result in rheumatoid arthritis

Furthermore, certain Dietary supplements with anti – oxidant properties have demonstrated

their effectives in alleviating arthritic conditions. For example, an nutritional supplement

composed of standardized lemon verbena (Aloysia triphylla, Lippia citriodora) and fish oil

omega-3 fatty acid administered to patients with arthritis enhanced physical performance and

substantially relief them of pain and joint stiffness associated with their condition. [45].

Treatment outcomes assessed by Western Ontario MacMaster (WOMAC) and Lequesne’s

scores respectively reduced by 53% and 78% after 9 weeks of treatment. These scores are

disease specific predictors of joint status and pain hence their reduction suggest improvement

in joint health and a reduction in pain [45].

The finding of this study therefore suggest that, a combination of fish oil omega-3 fatty acid

and lemon verbena could be an alternative for managing persons with joint degenerative

diseases.

3. A Natural Extract from Chicken Comb (Hyal-Joint®)

This is a novel natural extract derived from chicken comb. Hyaluronic Acid (HA)

concentrated in chicken combs is its active ingredient [46]. Several clinical trials have been

conducted on most dietary supplements for managing arthritis but no such trial was done on

HA based supplements [46]. To establish this, a pilot study was designed to investigate the

safety and treatment potential of chicken comb extract dubbed Hyal-Joint® which has high

amounts of HA. Patients experienced great reduction in pain, enhance physical performance

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and general life quality after 8weeks of administering 80mg/day of the dietary supplement

and these were significant compared to a placebo [46]. This was observed in twenty (20)

participants aged 40 or over with symptomatic OA equally randomised to receive either

80mg Hyal-Joint or placebo capsules daily for 8 weeks.

Assessed from baseline, both cohorts experienced significant improvements in pain, function

scale score and joint stiffness as measured by WOMAC scores. However, a larger change

was observed in the treatment group regarding the function scale and total symptoms.

The activity of Hyaluronic Acid (concentrated in Hyal-Joint) is linked to its presence in

synovial fluid and between cellular matrix of cartilage which functions in joint lubrication

[47, 48 49]. The low concentrations synovial fluid observed in OA patients can therefore

make one more susceptible to complications of the disease.

Methylsulfonylmethane (MSM)

Methylsulfonylmethane (MSM) is one of the non-essential nutrients; naturally produced in

the human body. It is synthesized from an organic solvent dimethyl sulfoxide [41] but small

quantities can be found in milk (pasteurized) and fresh fruits and vegetables [9]. MSM is one

of the dietary supplements used in managing OA due to its anti-inflammatory or free radical

scavenging activity [50].

Patients with OA of the knee showed signs of improvement in physical function and pain

after MSM was administered to them in a 12 week clinical trial [41]. In this study, 49 subjects

were randomised to receive either MSM (1.125g, three times daily) or a placebo. Over time

significant differences were observed in outcome measures between treatment group and the

placebo. E.g. WOMAC OA index for pain was significant (p = 0.03). The improvement

observed were however minimal and a clinical effect of MSM is yet to be evaluated. No side

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effects were recorded in this trial. However, other studies using about a double of the dose

used in this study recorded some adverse effects [51]

Another study had earlier in 2004, indicated a 33% reduction in pain assessment by the

Visual-analogue-scale (VAS) for pain [52] and these results were confirmed in 2006 by [51]

who reported substantial improvements in WOMAC pain score and physical function

impairments.

Since most OA medications such as COX-2 inhibiters are associated with harmful side

effects [53, 54], MSM can therefore be recommended for persons with OA as it is associated

with modest effects as shown in these studies.

The effect of MSM for especially long term use however needs to be probed further to

elucidate it true long term effect.

Phytalgic®

Phytalgic is a nutraceutical composed of Nettle, fish oil, zinc and vitamin E and it’s been

linked with the treatment of OA of the knee and hips [55].

A pilot clinical trial conducted in France in 2009 to evaluated the efficacy of Phytalgic on

knee/hip function and pain in patients with OA and its effect on the use of routine drugs

(Analgesic and NSAIDs) discovered that, Phytalgic supplements has the potential to reducing

disease outcomes measures over three months supplementation of three capsules daily [55].

It also resulted in greater than 50% reduction in how frequent patients used medications.

Eighty one participants diagnosed with OA of the knee and/or hip and frequently used

Analgesic and NSAIDs were randomised to receive either 3 capsules of Phytalgic daily or a

placebo (containing non fish oils) for three months. The average use of both Analgesic and

NSAIDs in the treatment group compared to placebo were significantly different (p-values

for treatment and placebo were respectively < 0.001 and = 0.02). Also, the average scores for

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function, pain and joint stiffness in the treatment cohort compared to placebo were

dramatically reduced and statistically significant. These finding demonstrate the potential of

Phytalgic as a treatment alternative for persons with OA. However, this is the only known

clinical trial on this novel nutraceutical and further trials are warranted to establish its true

efficacy and safety.

The action of Phytalgic has not yet been clearly elucidated although most of its constituents

are associated with the management OA, [55]. For instance, Omega-3 and/or Omega-6 fatty

acids in fish oils have been associated auto-immune diseases of the joints [56] and

degenerative joint diseases [57]. Some patients with OA also use Nettles (Urtical dioica) as

part of their treatment [58,59] and zinc is an important element required for proper

functioning of bone cells and it’s also known to have anti inflammatory potential [60].

The efficacy of vitamin E however remains a subject of controversy with some trial claiming

its effectiveness [33] while others are debunking it in both OA [35] and RA [34].

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SUMMARY OF SOME FUNCTIONAL FOODS AND NUTRACEUTICALS

Functional Food or

Nutraceutical

Key Findings

Study Design

Reference

Glucosamine and

chondroitin sulphate

Chondroitin Sulphate

(CS)

Glucosamine sulphate

and reparagen

Glucosamine based

supplement mixed with

Chondroitin sulphate

and micronutrient

antioxidants

No intervention recorded a clinically relevant

difference in outcome measures as compared with

placebo over 2 years. However, only glucosamine

and Celecoxib showed promising level of activity.

No differences in side effects recorded among

treatment groups and detrimental reactions were not

common.

Statistically relevant improvements in pain and knee

function were observed from the sixth week of the

study through to 24 weeks of the study

Within one, the treatment demonstrated progressive

and substantial improvements in Visual Analogue

Scores (VAS) and WOMAC scores in both

treatments.

Although some notable greater improvements in

some outcome variables were detected in the

treatment group compared to placebo, the evidence

were inconclusive

A 24-month DPC study

involving 662 patients with

knee OA

RDDA parallel-group study

using a non inferiority

design involving 837

patients

An 8 week RD Pilot Trial

with 95 participants.

A 16 week RDPCT study

involving 32 patients with

knee OA

Sawitzke, A. D. et at

(2010)

Fardellone P. et al

(2013)

Mehta, K. et al.

(2007)

Nakasone, Y. et al.

(2013)

Aquamin; A multi

mineral supplement

Patients in only the Aquamin group and the

Glucosamine groups experienced significant

improvements

A combination of Aquamin and Glucosamine

however, did not prove to be effective

A 12 week RDPCT

involving 70 persons

Frestedt, J.L. et al.

(2008)

Aflapin and 5-Loxin

5-Loxin® only

Aflapin and 5-Loxin proved effective in relieving

pain and improving on the joint function of patients

with osteoarthritis

Aflapin however, was more effective compared to

5-Loxin

Aflapin and 5-Loxin are safe for human consuming

5-Loxin reduces pain and improves physical

functioning significantly in OA patients

A 90-day RDP study with

60 OA persons

A 90-day RDP study with

Seventy-five OA patients

Sengupta, K. et al

(2010)

Sengupta, K. et al

(2008)

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Daniel A. Nyaaba Page 19

Aflapin Only

250 mg compared to 100 mg 5-Loxin® was more

effective with 7 days

100 mg Aflapin provided Substantial improvement

in physical function as well as pain scores were

observed with 5 days of usage

A 30-day RDP study with Sixty eligible OA subjects

Amar, A. V.et al

(2011)

S-Adenosyl

methionine (SAMe)

SAMe is as effective as Celecoxib in alleviating

pain and enhancing joint function in persons with

osteoarthritis of the knee. However, treatment effect

was delayed.

A 16 week RD cross-over

study, comparing SAMe

(1200mg) with Celecoxib

(Celebrex 200 mg)

Najm W. I. et al.

(2004)

Probiotics

Bacillus coagulans; Lactic acid producing

bacteria (LAB)

probiotics

Lactobacillus

rhamnosus GR-1 and

Lactobacillus reuteri

RC-14

Pain evaluation scores improvement from base line

was statistically significant in patients who received

the LAB probiotic (p=0.052)

No significant clinical effect of these Probiotics on

RA was recorded. But functionality was enhanced.

A 60 day RDP parallel-

design, clinical pilot trial in

45 adult men and women

with symptoms of RA 60

days

A 3 month double-blind,

placebo-controlled study using

30 subjects

Mandel, D.R. et al.

(2010)

Pineda, M. A et al.

(2011)

Vitamins

Vitamin E

Vitamin K

600 IU every other day of vitamin E was not

protective against women developing RA

500 IU/day Vitamin E was not helpful in

symptomatic knee OA.

No effect of vitamin K was observed in persons

with OA of the hand

A 10 year RDPCT

A six month RDP study

with 77 patients

A 3 year RCT in 378

subjects

Karlson, E. W. et al.

(2008)

Brand, C. et al.

(2001)

Neogi, T. et al (2008)

Plant and Animal

Extracts

Seaweed Extract

(Maritech®)

It alleviated symptoms of OA in patients over 12

weeks of and the effect was dose dependent

No detrimental effects were observed

A 12 week Clinical trial on

12 patients

Myers, S.P. et al

(2010)

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Daniel A. Nyaaba Page 20

Botanical Extracts (NP

06-1)

NP 06-1 was effective in relieving joint pains

associated osteoarthritis as measured by the LAI

score

An 8-week RDP pilot study

with 80 subjects

Oben, J. et al (2009)

AR7 Joint Complex

Had a short-term effect in treating pain in patients

with OA.

No significant adverse effect was noted in either

group.

A 12 week RDP study with

100 participants.

Xie, Q. et al. (2008)

A Natural Extract from

Chicken Comb

(Hyal-Joint®)

Patients experienced great reduction in pain,

enhance physical performance and general life

quality after 8weeks of administering 80mg/day of

the dietary supplement and these were significant

compared to a placebo

An 8 week pilot RDP on

twenty subjects aged ≥40

years with knee osteoarthritis

Kalman, S.D. et al.

(2008)

Supplements with

Antioxidant activity

Lemon verbena extract

and fish oil omega-3

fatty acid

Methylsulfonylmethane

(MSM)

substantially relief pain and joint stiffness

associated with their condition

Patients with OA of the knee showed signs of

improvement in physical function and pain after

MSM was administered to them in a 12 week

clinical trial

The improvement observed were however minimal

and a clinical effect of MSM is yet to be evaluated.

Another study had earlier in 2004, indicated a 33%

reduction in pain assessment by the Visual-

analogue-scale (VAS) for pain

Patients reported substantial improvements in

WOMAC pain score and physical function

impairments.

A 9 week RDPCT with 45

subjects

A 12 week prospective,

RDPCT 0n 49 subjects with

OA.

RCT

RTC

Caturla, N. et al.

(2011)

Debbi, E.M.et al.

(2011)

Usha P. et al. (2004)

Kim L.S. et al.

(2006)

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Phytalgic®

The average scores for function, pain and joint

stiffness in the treatment cohort compared to

placebo were dramatically reduced and statistically

significant

Greater than 50% reduction in how frequent patients

use both Analgesic and NSAIDs medications.

A 3 month RDPCT on

eight-one subjects

Jacquet, A. et al

(2009)

ABBREVIATIONS

DPC - Double- blinded Placebo Controlled

RDPCT - Randomised Double- blinded Placebo-Controlled Clinical Trial

RDDA - Randomised Double- blinded Double-placebo Action group

RDP - Randomised Double- blinded Placebo-Controlled

RD - Randomised Double- blinded

RCT - Randomised Clinical Trial

CONCLUSION

The evidence gathered from most of the clinical trials reviewed in this document strongly

suggest that, some functional foods and nutraceuticals are generally safe and can effectively

play the roles of the conventional medications used for the treatment of arthritis; which are

usually associated with unpleasant reactions. Whilst the treatment potentials of others (such

as Aflapin and 5-Loxin) can be felt within days, others such as S-Adenosyl methionine

(SAMe) and Maritech had delayed and dose- dependent treatment activity among others.

Users must however exercise caution as some combinations have proven ineffective or had

unfavourable effects.

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