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 ndanielayine@yahoo.com
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

(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

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

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

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)

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].

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.

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].

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

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.

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.

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.

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

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

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

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

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].

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
Seventy-five OA patients
Sengupta, K. et al
(2010)
Sengupta, K. et al
(2008)

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
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)

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)

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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