TGA Complaint, AC-GBKDH2XG/201 (6 July 2018 ......2018/07/06 · Naturopathica FatBlaster Clinical Weight Loss Diet Pill- Channel 7 News Blurb: FatBlaster Clinical is Australia's

TGA Complaint, AC-GBKDH2XG/201 (6 July 2018), Pharmacare Laboratories– Additional information requested

Page 1 of 22

The request (Simon Doctor, 9/08/2018)

“In your complaint regarding the Naturopathica FatBlaster products, you refer to the Panel’s

Determination of a complaint regarding the FatBlaster FatMagnet product, but it would assist if you

could identify which other FatBlaster products you wish to complain about and any particular

aspects of the advertising of them which may concern you, beyond an alleged lack of efficacy

evidence generally with these products”.

My response

As I said in my telephone conversation of 10 August 2018, I believe my 6 July 2018 complaint (AC-

GBKDH2XG/2018) contained the information you requested, especially the arrows that pointed to

specific claims that I alleged breached the Therapeutic Gods Advertising Code 2015.

While I did not detail specific sections of the Code that I alleged were breached for each product,

this could have readily been ascertained by your staff using the arrows provided. Your staff are paid

to investigate complaints; I am not.

Regardless, since it appears unlikely that you will satisfactorily progress my complaint without

additional information, this is now provided under protest.

On 6 July 2018 I complained about six Pharmacare listed weight loss products; I’ve now added three

more. I’ve also added several FatBlaster products, now formulated as foods (shakes, etc), which

largely contain the same ingredients as the listed products. These need to be referred by the TGA to

FSANZ and State Health Departments.1

I have previously noted that obesity is an increasing public health problem in Australia, the overweight and obese are a vulnerable population and such people are inevitably attracted to a pill promising a “quick fix”. The sponsor of these products, Pharmacare Laboratories (Cat Media) has exploited this vulnerability by introducing a succession of listed products, containing various ingredients (mainly under the FatBlaster name), all implying by their name, claims and product illustrations that they will produce clinically useful weight loss, over and above that obtained by diet and exercise alone.

I first raised these issues in the medical literature 10 years ago (attached).2 I have suggested the TGA should target complementary medicines claiming to assist weight loss as an important priority for their enhanced post-marketing monitoring program.3

Despite at least 30 upheld complaints by the Complaint Resolution Panel (CRP) concerning listed weight loss products over the last 10 years the TGA has done nothing to tackle this systemic problem. This is particularly reprehensible as ongoing misleading and deceptive claims for these products are likely to divert consumers from more evidence-based weight loss programs.

The sponsor has ignored numerous upheld complaints &/or made only minor changes to wording &/or introduced new products with different ingredients making similar claims. In addition, Pharmacare Laboratories has the unenviable reputation of the having the most upheld complaints of any sponsor of complementary medicines over the life of the CRP.

A formal complaint about your request, and the failure of the TGA to address longstanding misleading and deceptive claims for listed weight loss products, will be sent to the Health Secretary and Health Minister.

1 https://compliance.tga.gov.au/advertising-complaint 2 https://www.ncbi.nlm.nih.gov/pubmed/18205557 3 https://www.tga.gov.au/compliance-and-education-listed-medicines

https://compliance.tga.gov.au/advertising-complaint

https://www.ncbi.nlm.nih.gov/pubmed/18205557

https://www.tga.gov.au/compliance-and-education-listed-medicines


Page 2 of 22

Meanwhile, even though the TGA has many more resources that me, you now want more specific details of the advertising claims about the appended products that concern me.

I allege that the ingredient combinations in the following products lack evidence to substantiate the indications and claims made, and their continued promotion, including the product names and pack illustrations, represent repeated, multiple breaches of the Therapeutic Goods Advertising Code 2015. I also note that many specific indications on the product ARTG Public Summary Documents are equally misleading and deceptive. The details follow.

Specific concerns (from the most recent products listed on the ARTG to the earliest)

1. ARTG ID 299770 Product name: Naturopathica Reducta Sugar Craving Mints Active ingredients: Gymnema sylvestre, zinc citrate dihydrate Sponsor: Cat Media Pty Ltd

https://www.health365.com.au/naturopathica-reducta-mints-30s

http://tga-search.clients.funnelback.com/s/search.html?collection=tga-artg&profile=record&meta_i=299770

https://www.health365.com.au/naturopathica-reducta-mints-30s


Page 3 of 22

The claims:

• A unique formulation of Gymnemic and Zinc that bind to the sweet receptors in your

mouth to help reduce sugar cravings in minutes

• Helps stop sugar cravings so you can avoid those tempting sweet snacks.

• Use Reducta Mints:

o Between meals to avoid snacking

o To curb your appetite

o To avoid dessert temptation

o Right after a snack to reduce the desire for more.

There is good scientific evidence that the leaves of Gymnema sylvestre R.Br. (Asclepiadaceae)

can inhibit the sweet taste of sucrose, sodium saccharin, cyclamate and other compounds.4

However, I could find no scientific literature that translated this effect into “reducing sugar

cravings”, “avoiding snacking”, “curbing appetite”, “avoiding desert temptation” or “reducing

the desire for more (snacks)”. Nor could I find any evidence that zinc in this “unique formula”

would produce any additional effect.

While it is reasonable to claim that Gymnema sylvestre can inhibit the taste of sugar, I allege that

above the claims go well beyond this scientific fact and thus breach the Therapeutic Goods

Advertising Code 2015, s.4(10(b), 4(2)(a) & 4(2)(c).

In addition, the above advertisement lacks mandatory warning statements, a breach of s.6(3) of

the Code and the advertisement is categorised under “Weight management” yet it lacks the

necessary mention of the importance of an energy-controlled diet and physical activity, a s.7(3)

breach of the Code.

4 https://www.ncbi.nlm.nih.gov/pubmed/24511547



Page 4 of 22

2. ARTG ID: 295575 Product name: FatBlaster Clinical Active ingredients: Curcuma longa, Moringa oleifera, Murraya koenigii Sponsor: Cat Media Pty Ltd

Ingredients: Each capsule contains: Curcuma longa (Tumeric) ext. equiv. to dry rhizome 2.925g; Moringa oleifera (Drumstick leaves) ext. equiv. to dry leaf 2.16g.; Murraya koenigii (Curry leaves) ext. equiv. to dry leaf 945mg.

https://www.fatblaster.com.au/fatblaster-clinical-60s

https://www.fatblaster.com.au/clinical-weightloss

Now

unqualified


https://www.fatblaster.com.au/fatblaster-clinical-60s



Page 5 of 22


Video at: https://youtu.be/IcU0i5yC1eU

Claims and comment

• The Name: FatBlaster. This product does not “blast” fat. A s.4(1)(b), 4(2)(a), 4(2)(c) Code breach.

• The body figures illustrated above are not typical of the results likely to be achieved. A 4(2)(c) Code breach.

• Australia's latest breakthrough in weight loss to help you lose up to 6x more weight than diet and exercise alone. In a 2016 Clinical trial, the FatBlaster Clinical formula5 was shown to help users lose up to 6x more weight than dieting and exercise alone. FatBlaster Clinical was also shown to help reduce centimetres from hips and waist. Scientifically shown to help reduce centimetres from your hips and waist. See comment on clinical trial below.

• Channel 7 news item (a placed advertisement is not bone fide news, see below).

5 When used in conjunction with diet and exercise.


https://youtu.be/IcU0i5yC1eU


Page 6 of 22

https://youtu.be/IKOCQnb1MI0

Naturopathica FatBlaster Clinical Weight Loss Diet Pill- Channel 7 News

Blurb: FatBlaster Clinical is Australia's latest breakthrough in weight loss to help you lose up to 6x

more weight than diet and exercise alone.

Transcript: “It’s the holy grail for some looking to shed weight. A tablet claims to boost metabolism

and breakdown fat. Doctors behind the product say it's different to other weight loss products

because it backed by scientific evidence”.

Comment: the terms “latest breakthrough” and “holy grail” are a s.4(2)(a) & 4(2)(c) Code breach.

The “doctor” was a PhD employed by PLT Health Solutions, marketer of LI85008F (SLENDACOR™).

As.4(2)(c) and 4(6)(iii) Code breach. See comment on clinical trial below.


Transcript: “This winter his diet remains the same, but the scales have shifted, from this down to

this”.

Comment: A deceptive and misleading visual, a s.4(2)(a), 4(2)(c) Code breach. Also s.7(3) as this

statement does not “balance” product claims with the need for an energy-controlled diet and

physical activity.




Page 7 of 22


Transcript: "Usually I'd gain 10 in winter and this winter I've lost 10 kilos".

Comment: Screen caption implies “Rob” was part of the published clinical trial when he was not

(s.4(2)(c) Code breach). In addition, the claimed loss of 10 Kg in 8 weeks without diet and exercise is

not typical of the published trial results not does it “balance” product claims with the need for an

energy-controlled diet and physical activity (s.7(3) Code breach). Also, potential s.4(7) breach;

testimonial needs verification by a statutory declaration.


Transcript: “For the last 8 weeks Rob has trialled a weight loss pill claimed to boost the body’s ability

to shed fat using a formula of three botanical ingredients”.

Comment: Implies “Rob” was part of the published clinical trial when he was not (s.4(2)(c) Code

breach).




Page 8 of 22


Transcript: Dr Barbara Davis, PTL Health Solutions, "It prevents the maturation of fat cells so that

they don't hold as much fat; also helps to break down fat and eliminate it from the body".

Comment: Endorsement by an implied health professional, a s4.(6)(b)(iii) Code breach.


Transcript: “A 16-week study …. the group who had received the active ingredient lost over 5 kg, up

to 6 times more that the placebo group….”

Comment: See notes on the clinical trial below.




Page 9 of 22


Transcript: “FatBlaster Clinical is a different formulation from the original FatBlaster…”


Transcript: “The supplement is being rolled out in Australian pharmacies.”




Page 10 of 22


Transcript: “And while some experts agree it may assist in weight loss, they’re skeptical it’s worth

the $70 a month spend.”

Comment: That is not what Dr Fuller (or any other “expert”) said, a s.4(1)(b), 4(2)(a) & 4(2)(c) Code

breach.

Dr Nick Fuller: “It’s not that miracle weight loss cure. It’s only achieving the same amount of weight

loss as if someone went out and changed several aspects of their lifestyle”. “Like diet and exercise”.

https://www.fatblaster.com.au/



Page 11 of 22


Comment: the claimed loss of 9 Kg (Karen) and 7 Kg (Rob) in 8 weeks without mention of diet and

exercise is not typical of the published trial results not does it “balance” product claims with the

need for an energy-controlled diet and physical activity (s.7(3) Code breach). In the video (above)

Rob claimed a loss of 10 km, now its 7kg. Also, a potential s.4(7) breach; both testimonials needs

verification by a statutory declaration.

Clinical trial: The strong claims, “Australia's latest breakthrough in weight loss”, “lose up 6x more weight than dieting and exercise alone” and “reduce centimetres from hips and waist” were attributed to a “2016 Clinical trial” which lacked information (in some advertisements and the ARTG Public Summary) on the authors or where to find the study.

The study is appended.6 It was conducted in Bangalore, (Bengaluru) India, funded by the product developer, Laila Nutraceuticals, India and the product promotor, PLT Health Solutions (SLENDACOR™), who each provided an author of the paper.

It involved 150 overweight Indian participants (body mass index 27-29.9 kg/m2, 29.3% male; ages 21-50 years) randomized into placebo (n =70) and intervention (n =70) groups studied for 16 weeks.

The dose of the three active herbal ingredients (LI85008F) was two 450 mg capsules taken one before breakfast and one before dinner. Participants were also advised to walk for 30 min, 5 d/week, and maintain a diet of ~1800 kcal/d as instructed by a dietitian.

At the end of the trial period, the LI85008F supplemented group showed significant reductions in body weight: (mean ± SD: 5.36 ± 1.769 vs. 0.87 ± 1.381 kg; P < 0.0001) and BMI (mean ± SD: 2.05 ± 0.693 vs. 0.34 ± 0.559 kg/m2; P < 0.0001), compared with placebo. Significant reductions in waist and hip circumferences, and a 2.08-fold reduction of waist/hip ratio, were also noted in the LI85008F supplemented group.

While the results were impressive (some would say too good to be true) the study was conflicted by the commercial interests involved, it was performed on an Indian (not Australian) population and the results have yet to be replicated.

6 https://www.ncbi.nlm.nih.gov/pubmed/29923305



Page 12 of 22

In addition, I would have expected the placebo group to lose more weight on the diet and exercise regime. But there was no monitoring of what the participants ate. Without this, it is not possible to say that the supplement was the effective component. Did those taking the supplement eat less?

Several side effects were labelled as 'minor' but included gastritis, loose stool and dehydration. Although the authors said there was no difference in these side effects between the groups, no data was given. We need to know how common the side effects were. Any of these three could lead to changes in appetite and/or weight.

The results for much of what they measured also had huge confidence intervals – e.g. fat mass, lean mass, LDL and other blood fats. They show only that the variation was too great to draw any valid conclusion.

I submit that this trial does not justify the strong promotional claims made for an Australian audience especially as the promotion merely says, “use in conjunction with a healthy, energy-controlled diet and exercise program” and does not spell out the ~1800 kcal/d diet and the 5 d/week 30 min walk exercise regime used in the trial.

In summary, taking all the above into account, I allege breaches of the Therapeutic Goods

Advertising Code 2015, s.4(1)(b), 4(2)(a), 4(2)(c), 4(4), 4(6)(iii), and.7(3). Also, a potential s.4(7)

breach.


Page 13 of 22

3. ARTG ID 295230 Product name: Reducta Active ingredients: Caralluma adscendens var. fimbriata, Crocus sativus Sponsor: Cat Media Pty Ltd

https://www.pharmacydirect.com.au/Product/naturopathica-reducta-hunger-reduction-40-tablets-28349.aspx

Claims:

• Hunger Reduction 40 Tablets

• Reduce Hunger & Snacking

• Reducta helps you eat less, therefore giving you more control over your hunger.

This product has had 3 previous complaints upheld by the Complaint Resolution Panel (CRP).7 Determination 2013-02-027 noted breaches of the Code, s.4(1)(b), 4(2)(a) & 4(2)(c). The CRP specifically asked the sponsor to withdraw any representations that the advertised product can reduce hunger. Because of non-compliance, this recommendation was sent to the Secretary on 13 Feb 2014.

Following investigation, the Delegate's decision was made on 11 April 2014.8 The Delegate ordered Pharmacare Laboratories Pty Ltd to:

7 http://www.tgacrp.com.au/complaint-register/?_search=Reducta 8 https://www.tga.gov.au/advert-complaint/reducta-pharmacare-laboratories-pty-ltd-complaint-no-2013-02-027




http://www.tgacrp.com.au/complaint-register/?_search=Reducta

https://www.tga.gov.au/advert-complaint/reducta-pharmacare-laboratories-pty-ltd-complaint-no-2013-02-027

https://www.tga.gov.au/advert-complaint/reducta-pharmacare-laboratories-pty-ltd-complaint-no-2013-02-027


Page 14 of 22

“withdraw any representations, including implied representations, that the product can be used for hunger reduction, unless those representations are worded to the effect that Caralluma fimbriata has been traditionally used for hunger reduction in India in times when food was scarce”.

On the 24 April 2014 PharmaCare Laboratories Pty Ltd provided written assurance to the delegate of the Secretary that they would comply fully with the regulation 9 orders made on 11 April 2014.

I allege that the sponsor has wilfully breached that order by continuing to claim that this product can reduce hunger & snacking with no mention of “traditional” indications. In addition, the most recent scientific review I could find noted:

“Only one drug from C. fimbriata has been released under the trade name Genaslim for body weight control, but the clinical trials on the product does not support appetite-suppressant activity in the extract even though GRAS status has been given to the extract of C. fimbriata (Slimaluna)”.9

See also: “TGA, once again, fails to reign in shonky weight-loss product”.10

In short, ongoing breaches of the Code, Code, s.4(1)(b), 4(2)(a) & 4(2)(c).

9 https://www.ncbi.nlm.nih.gov/pubmed/22191633 10 https://theconversation.com/tga-once-again-fails-to-reign-in-shonky-weight-loss-product-10227


https://theconversation.com/tga-once-again-fails-to-reign-in-shonky-weight-loss-product-10227


Page 15 of 22

4. ARTG ID: 278976 Product name: Naturopathica FatBlaster Triple-Tea Fat Burner Active ingredients: Camellia sinensis, Paullinia cupana Sponsor: Cat Media Pty Ltd

https://fatblaster.com.au/fatblaster-triple-tea-fat-burner

Comment: The name FatBlaster Triple-tea fat burner is deceptive and misleading (this product does

not blast or burn fat) as is the prominent claim “Fat Burner”. The claims, “Burn more fat” and

“Increase thermogenesis”, “fat burning tea ingredients” are also misleading, deceptive as there is no

good evidence this product produced clinically relevant weight loss. The claim, “FatBlaster Triple-

Tea Fat Burner is high in Epigallocatechin gallate (EGCG) which can help metabolic processes and

assist in fat burning” is not appropriate or understandable scientific information. Finally, the

illustration is not typical of the results likely to be achieved.

See also: "Science or Snake Oil: do skinny teas boost weight loss".11 Cochrane review: "Green tea for

weight loss and weight maintenance in overweight or obese adults" 12

In short, breaches of the Therapeutic Goods Advertising Code 2015, s.4(1)(b), 4(2)(a), 4(2)(c) and

4(4).

11 https://theconversation.com/science-or-snake-oil-do-skinny-teas-boost-weight-loss-87353 12 https://www.cochrane.org/CD008650/ENDOC_green-tea-for-weight-loss-and-weight-maintenance-in-overweight-or-obese-adults


https://fatblaster.com.au/fatblaster-triple-tea-fat-burner

https://theconversation.com/science-or-snake-oil-do-skinny-teas-boost-weight-loss-87353

https://www.cochrane.org/CD008650/ENDOC_green-tea-for-weight-loss-and-weight-maintenance-in-overweight-or-obese-adults

https://www.cochrane.org/CD008650/ENDOC_green-tea-for-weight-loss-and-weight-maintenance-in-overweight-or-obese-adults


Page 16 of 22

5. ARTG ID: 229539 Product name: FatBlaster Garcinia Max Active ingredients: Hydroxycitrate complex Sponsor: Cat Media Pty Ltd

https://www.fatblaster.com.au/fatblaster-garcinia-max

Etc.

Comment: There have been 14 complaints upheld by the CRP for products containing Garcinia

cambogia. Determination 2014-11-006 has a nice review of the literature and non-compliance

resulted in a recommendation to the Secretary that clearly has had no effect on other sponsors as

seen in the advertisement for this product.

The name FatBlaster Garcinia Max is deceptive and misleading (this product does not blast fat) The

claim that HCA “mobilises fat storage” and “supports fat consolidation” lacks clinical relevance. The

illustration is not typical of the results likely to be achieved and the testimonial needs verification by

a statutory declaration.

See also: “Science or Snake Oil: is Garcinia cambogia the magic weight-loss pill it’s hyped up to

be?”13 “Five supplements that claim to speed up weight loss – and what the science says”.14

In short, breaches of the Therapeutic Goods Advertising Code 2015, s.4(1)(b), 4(2)(a), 4(2)(c) and

possibly 4(7).

13 https://theconversation.com/science-or-snake-oil-is-garcinia-cambogia-the-magic-weight-loss-pill-its-hyped-up-to-be-59822 14 https://theconversation.com/five-supplements-that-claim-to-speed-up-weight-loss-and-what-the-science-says-89856


https://www.fatblaster.com.au/fatblaster-garcinia-max

https://theconversation.com/science-or-snake-oil-is-garcinia-cambogia-the-magic-weight-loss-pill-its-hyped-up-to-be-59822

https://theconversation.com/science-or-snake-oil-is-garcinia-cambogia-the-magic-weight-loss-pill-its-hyped-up-to-be-59822

https://theconversation.com/five-supplements-that-claim-to-speed-up-weight-loss-and-what-the-science-says-89856

https://theconversation.com/five-supplements-that-claim-to-speed-up-weight-loss-and-what-the-science-says-89856


Page 17 of 22

6. ARTG ID: 212760 and ARTG ID: 227714 Product name: FatBlaster Max Active ingredients: chromic chloride hexahydrate, Camellia sinensis, Chromium picolinate, Citrus aurantium, Coffea canephora, Cyanocobalamin, Eleutherococcus senticosus, Fucus vesiculosus, Garcinia quaesita, Ilex paraguariensis, Nicotinamide, pyridoxine hydrochloride, Paullinia cupana, Plantago afra, Plectranthus barbatus, Riboflavin, Thiamine nitrate Sponsor: Cat Media Pty Ltd.

https://www.fatblaster.com.au/fatblaster-max-60s

Etc.

Comment: the CRP has upheld 6 previous complaints about products with this name. I allege the

name FatBlaster Max is deceptive and misleading (this product does not blast fat) as is the claim

“ultimate weight loss”.

The claims, “Burn more fat”, “Burn more calories”, “new, improved formula”, “FatBlaster Max is for

those who want to take their weight loss to the next level” are not supported by evidence about the

ingredients while “trigger thermogenesis” is not appropriate or understandable scientific

information. and lacks clinical relevance. The illustrations are not typical of the results likely to be

achieved and the testimonial needs verification by a statutory declaration.

In short, breaches of the Therapeutic Goods Advertising Code 2015, s.4(1)(b), 4(2)(a), 4(2)(c), 4(4)

and most likely 4(7).



https://www.fatblaster.com.au/fatblaster-max-60s


Page 18 of 22

7. ARTG ID 172079 Product name: Naturopathica FatBlaster Diuret Active Ingredients: Apium graveolens, Arctostaphylos uva-ursi, Petroselinum crispum, Taraxacum officinale Sponsor: Cat Media Pty Ltd

https://www.fatblaster.com.au/fatblaster-diuret-60s

Etc.

Comment: The CRP has upheld 5 previous complaints about this product.15

I allege the name FatBlaster is deceptive and misleading (this product does not blast fat).

In addition, the advertisement does not state (as the ARTG public summary does) that the ingredients are “traditional” diuretics.

Furthermore, “rapid slimming” by the use of diuretics removes water, not fat and is potentially dangerous.

Finally, the illustrations coupled with the claim “flatten your tummy” are not typical of the results likely to be achieved while the testimonial is most unlikely to relate to this product or be typical of results achieved.

In short, breaches of the Therapeutic Goods Advertising Code 2015, s.4(1)(b), 4(2)(a), 4(2)(c), 4(4) and most likely 4(7).

15 http://www.tgacrp.com.au/complaint-register/?_search=Diuret


https://www.fatblaster.com.au/fatblaster-diuret-60s

http://www.tgacrp.com.au/complaint-register/?_search=Diuret


Page 19 of 22

8. ARTG ID: 167323 Product name: Naturopathica FatBlaster Active ingredients: Camellia sinensis, Chromium picolinate, Citrus aurantium, Cyanocobalamin, potassium iodide, pyridoxine hydrochloride, Panax ginseng, Paullinia cupana, Psyllium Husk Powder, Riboflavin, Thiamine nitrate, Zingiber officinale Sponsor: Cat Media Pty Ltd

https://www.fatblaster.com.au/fatblaster-60s

Etc.

Comment: At least 11 previous complaints upheld by the CRP.16

I allege the name FatBlaster is deceptive and misleading (this product does not “blast fat”) as is the

claim “expert weight loss.

The claim, “trigger thermogenesis” is not appropriate or understandable scientific information.

The claim, “supporting increased fat burning” is not on the ARTG and has lacks clinical relevance.

Finally, the illustrations are not typical of the results likely to be achieved, and the testimonial needs

verification by a statutory declaration.

In short, breaches of the Therapeutic Goods Act 1989, s.22(5) and the Therapeutic Goods Advertising

Code 2015, s. 4(1)(b), 4(2)(a), 4(2)(c), 4(4) and possibly 4(7).

16 http://www.tgacrp.com.au/complaint-register/?_search=fatblaster


https://www.fatblaster.com.au/fatblaster-60s

http://www.tgacrp.com.au/complaint-register/?_search=fatblaster


Page 20 of 22

9. ARTG ID: 145959 Product name: Naturopathica FatBlaster FatMagnet Active ingredients: Ascorbic acid, poliglusam, Psyllium Husk Powder Sponsor: Cat Media Pty Ltd

https://www.fatblaster.com.au/fatblaster-fatmagnet-fat-absorber-60-pack

Etc.

Comment: At least 4 previously upheld complaints by the CRP about this product.17,18

I allege the name FatBlaster FatMagnet is deceptive and misleading as this product does not blast fat

nor attract fat out of the body as the name (and illustration) implies.

The illustration is not typical of the results likely to be achieved and the claim “can assist adults who

are actively wanting to lose weight” lacks clinical evidence for this specific product formulation.

In short, breaches of the Therapeutic Goods Advertising Code 2015, s.4(1)(b), 4(2)(a), and 4(2)(c).

17 http://www.tgacrp.com.au/complaint-register/?_search=Fat%20magnet 18 http://www.tgacrp.com.au/complaint-register/?_search=Fatmagnet

https://www.fatblaster.com.au/fatblaster-fatmagnet-fat-absorber-60-pack

http://www.tgacrp.com.au/complaint-register/?_search=Fat%20magnet

http://www.tgacrp.com.au/complaint-register/?_search=Fatmagnet


Page 21 of 22

Products reformulated as foods

The following FatBlaster products are now formulated as foods (shakes, etc). They largely contain

the same ingredients as the listed products. These need to be referred by the TGA to FSANZ and

State Health Departments.




Page 22 of 22

https://www.fatblaster.com.au/products?p=2&weight_loss_category=5


15 August 2018

Dr Ken Harvey AM

Associate Professor

Department of Epidemiology and Preventive Medicine School of Public Health and Preventive Medicine

Monash University

Alfred Campus

553 St Kilda Rd

Melbourne VIC 3004

Mobile: +61 419181910

Email: [email protected]

WWW: www.medreach.com.au



mailto:[email protected]

http://www.medreach.com.au/

PHARMACEU TICALS AND PRESCR IBIN G

Commercialism, choice and consumer protection: regulation of complementary medicines in Australia

Ken J Harvey, Viola S Korczak, Loretta J Marron and David B Newgreen

The Medical Journal of Australia ISSN: 0025-729X 7 January 2008 188 1 21-25©The Medical Journal of Australia 2008www.mja.com.auPharmaceuticals and Prescribing

organisations such as CHOICE.2

Here, we review the regulatory requirements forpare weight-loss products listed on the ARTG wpharmaceutical products, analyse complaint proadvocate policy change. We have focused on weigucts because of widespread concern about an obesit

MJA • Volume 188 Numb

ABSTRACT

• Controls on the supply and promotion of complementary medicines in Australia are weak.

• We used weight-loss products as an example to compare the regulation in Australia of listed complementary medicines and registered pharmaceutical products.

• Complementary medicines are listed without evaluation for efficacy, while conventional pharmaceutical products are registered after evaluation for quality, safety and efficacy.

• From 1996 to 2006, over 1000 “weight-loss” products were listed on the Australian Register of Therapeutic Goods; most contained multiple unevaluated ingredients (herbs, vitamins, minerals) of dubious efficacy. Over the same period, 10 conventional medicines were registered; each contained one evaluated ingredient of proven efficacy.

• The number of listed weight-loss products (and complaints about their promotion) is increasing. These appear to be a direct consequence of the decision not to evaluate listed products for efficacy and the lower fees for listing a product, compared with registration.

• Complaint procedures (now overloaded) are no substitute for adequate regulation at the time of market entry.

• Regulatory reform of listed and homoeopathic products is

MJA 2008; 188: 21–25required.

omuscoC
plementary and alternative medicines (CAMs) are being
ed increasingly in Australia, often in conjunction withnventional medicines.1 While the demand for CAMs is

growing, the regulatory framework is weak. The electronic lodge-ment facility, introduced in 1996, has made it easier to place newCAMs on the Australian Register of Therapeutic Goods (ARTG).Concern about the regulation of CAMs has been growing among

CAMs, com-ith registeredcedures andht-loss prod-y “epidemic”,

extensive advertising of the products and the large number onthe market.

Regulation of therapeutic goods in AustraliaIn 1989, the federal Parliament passed the Therapeutic Goods Act1989 (Cwlth), which created the ARTG. The ARTG has two parts:one for “registered goods” and the other for “listed goods”. Somegoods captured by the Act are classified as “exempt goods” andare not entered in the ARTG (ss. 9A, 18). Box 1 shows thedifferences between the various categories of therapeutic goods.

“Registered” medicines are considered to be of relatively higherrisk and are individually evaluated by the Therapeutic GoodsAdministration (TGA) for quality, safety and efficacy beforemarket entry. “Listed” medicines are considered to be of relativelylower risk (Box 2).3

Most, but not all, CAMs are listed medicines.4 Initially, theTGA did not require sponsors to have evidence to supportclaims made about their products. In 1999, concern thatimprobable therapeutic claims were being made about CAMs ledto the introduction of a requirement that sponsors hold substan-tiating evidence.5 Further, since a report by the Expert Commit-tee on Complementary Medicines in the Health System, arandom sample of about 20% of new listings is said to beassessed each year for compliance with TGA requirements.6

Both these measures have been introduced to increase monitor-ing of CAMs.

In 1991, the government introduced fees and charges toindustry for services provided by the TGA, such as ARTGapplications, good manufacturing practice inspections andannual licensing. The aim was to achieve 50% cost recovery. In1998, the government determined that 100% of costs would berecovered.7 Illustrative TGA fees (at 1 July 2007) were $170 200for registering and evaluating a new prescription medicine (a newchemical entity); $990 for registering and evaluating an over-the-counter product or CAM (plus $6570–$46 000, depending onthe number of pages of data submitted); and $540 for listing amedicine. The annual charge for a registered (non-biological)prescription medicine was $3030; for a registered over-the-counter product, conventional or CAM, $920; and for a listedmedicine, $690.7

Sponsors self-assess their medicines as being listable using theweb-based electronic listing facility (ELF) of the ARTG. The ELFsystem automatically checks that the ingredients entered areconsistent with those allowed in listed medicines and asks thesponsors to certify that they hold evidence to support the indica-tions (and thus claims) made. Sponsors may pick either a codedindication such as “May aid or assist weight loss . . .” or a customindication entered as free text in a memo field. More than oneentry into either field is allowed. After payment of a fee, the ELFsystem automatically generates an “AUST L” number and acertificate of listing.

Since the introduction of the ELF, the time taken to list a producthas been reduced from around 5 months to 10 days or less forabout 90% of applications.8

Complaints from the public about listed products need to besubmitted to various authorities, as summarised in Box 3.9

In February 2007, the Australian Government reintroduced aprovision of the Therapeutic Goods Advertising Code, which hadexisted before August 2005, prohibiting health care professionalsfrom endorsing therapeutic goods in advertisements to consumers.This provision took effect from 8 March 2007, but allowed existingadvertisements to continue for either 2 years after approval (eg, inprint) or 1 year if approval had not been required (eg, Internetadvertisements).10

er 1 • 7 January 2008 21


An example: weight-loss productsIn Australia, both listed and registered weight-loss products areavailable. To determine the numbers of each and compare them,we asked the TGA to search the ARTG for registered or listedproducts with the indication “weight loss”, or similar, for theperiod 1996 to 2006. We then supplemented the list by searchingthe shelves of pharmacies and health food shops and AustralianInternet sites. Because of problems encountered, the TGA madeavailable a subset of the ARTG database so that we could refinetheir search for weight-loss products. For the registered and listedproducts found, we compared the therapeutic claims with thepublished evidence. The website of the Therapeutic Goods Adver-tising Code Council was used to identify complaints and selectillustrative case studies.

Products identifiedThe initial search output received from the TGA failed to showsome registered weight-loss products, such as orlistat (Xenical[Roche]) and sibutramine (Reductil [Abbott]). It also failed toshow many listed CAMs that were being actively promoted forweight loss.

Some of these problems resulted because the ELF systemallowed sponsors of listed products to enter information into theARTG in free text without verification by TGA staff. Some non-standard indications had been used for weight-loss products (suchas “thermogenic”, “body sculpting”, “reduce carb cravings”), whichmade a complete search for such products difficult, if not imposs-ible.

Our own search found over 1000 new weight-loss productslisted on the ARTG from 1996 to 2006. New listings generallyincreased over the period, from 45 in 1996 to 144 in 2006. Mostcontained multiple ingredients (herbs, vitamins, minerals).Homoeopathic products are not included on the ARTG. Over thesame period, 10 conventional medicines for weight loss wereregistered with the ARTG, each containing one ingredient, (orli-stat, diethylpropion, phentermine, sibutramine). All these sub-stances are officially scheduled poisons, and products containingthem are registered for the management of obesity, unless the

1 Contrasting requirements of the Therapeutic Goods Administration (TGA) for different categories of goods

RequirementRegistered goods

(pharmaceutical products)Listed goods

(complementary medicines) Exempt goods

Label designation AUST R AUST L na

Compliance with Code of Good Manufacturing Practice

Yes Yes No

Manufacturers licensed by TGA Yes Yes No

Efficacy evaluated by TGA Yes No No

Stability (shelf-life) evaluated by TGA Yes No No

Individual ingredients evaluated for safety by TGA

Yes Yes Some (eg, those in antiperspirants, fluoride toothpastes)

Examples All medicines included in a poisons schedule,all PBS medicines,

all other medicines not listed or not exempt goods

Most herbal preparations, vitamins, minerals, glucosamine, some homoeopathic medicines

(if the sponsors so choose), export goods

Homoeopathic medicines, extemporaneously dispensed

medicines, dandruff shampoos, antiperspirants,

fluoride toothpastes

na = not applicable. PBS = Pharmaceutical Benefits Scheme. ◆

2 Main criteria used by the Therapeutic Goods Administration for listed complementary medicines (with the exception of homoeopathic products)

• They may contain only ingredients approved for use in listed medicines (those with well established quality and safety profiles);

• They must be labelled and advertised only for indications consistent with low risk (eg, symptomatic relief of non-serious diseases, disorders and conditions) and must not be indicated for the treatment of a serious form of a disease, condition, ailment or defect as specified in the Therapeutic Goods Advertising Code;

• There must be evidence (which can be either traditional or scientific), held by the sponsor of the product, to support any claim that the sponsor makes relating to the medicine; and

• They do not contain substances that are scheduled in the Standard for the Uniform Scheduling of Drugs and Poisons or otherwise restricted (eg, included in Part 4 of Schedule 4 of the Therapeutic Goods Regulations 1990). ◆

3 Bodies handling complaints about listed products and registered over-the-counter products

Complaint Regulation

About product quality or claims made on the pack or pack insert

Therapeutic Goods Administration’s Office of Complementary Medicines

About promotional claims made in specified media (television, radio, Internet, newspapers, magazines, outdoor signs and cinema)

Complaints Resolution Panel assesses concerns against the Therapeutic Goods Advertising Code

About other advertising, such as pharmacy window displays, brochures, leaflets and catalogues

Complaints Resolution Committee of the Complementary Healthcare Council of Australia or Australian Self-Medication Industry’s Complaints Panel

22 MJA • Volume 188 Number 1 • 7 January 2008


product is for export. Those containingorlistat and sibutramine have been fullyevaluated. Phentermine-containing medi-cines were “grandfathered” on to theARTG because they were already on theAustralian market when the Act took effectin February 1991. Diethylpropion is nolonger marketed. The safety and efficacy ofthese agents has been comprehensivelyreviewed.11

Thus, sponsors could decide not tomarket products they had placed on theARTG or to take them off the market butleave them on the ARTG. Taking intoaccount these limitations, we found about100 times as many listed weight-lossproducts on the ARTG as registered prod-ucts. It is not possible to be too specificabout numbers because there were con-founding factors, such as the inclusion inthe listed goods part of the ARTG ofprescription-only medicines that weredestined for export.

In our opinion, the indications forweight-loss products listed on the ARTG(and thus their promotional claims) wereoften not in accord with the limited scien-tific evidence available. Furthermore, thenumber of such listed products is increas-ing each year at a much greater rate thanregistered products. It is possible that thishas been influenced by the decision not toevaluate listed products for efficacy andalso the lower fees for listing a productcompared with registration.

A typical weight-loss product

An example of a publicly available, listedweight-loss product is shown in Box 4. Weare unaware of publicly available evidencefrom clinical trials to support the thera-peutic claims made for this product or formany other listed (and homoeopathic)weight-loss products. Several systematicreviews have evaluated the commonlyincluded ingredients and have concludedthat, at best, more definitive clinical trialsare required before conclusions can bedrawn.12,13 While these products are ofrelatively low risk, some herbal ingredi-ents can cause harm by themselves and also by interacting withconventional medicines; both kinds of event may be under-reported.14,15

The Complaints Resolution Panel found that the claims madeabout the illustrated product, Xantrax (Hershel-Beck Laborato-ries), breached the Therapeutic Goods Advertising Code as theywere misleading and likely to arouse unwarranted and unrealisticexpectations of product effectiveness.16 In our experience, itusually takes 3 to 4 months for submitted complaints to beadjudicated by the Complaints Resolution Panel and several more

months before the results are made public.Meanwhile, promotional campaigns con-tinue. In addition, the sanctions imposedappear ineffectual, as shown by the fact thatsome companies repeatedly breach theTherapeutic Goods Advertising Code. Forexample, from March 2004 to November2007, the sponsor of Xantrax, Cat Media PtyLtd, has had at least 28 complaints about itsproduct s, 22 of which have beenupheld.16,17 In 2006, the Panel received over350 complaints, more than twice thenumber received in 2005. Of these, 170have been finalised and 100 are still beingprocessed, 60 concerning homoeopathicproducts and which were referred to theTGA, and 22 referred to other bodies. Thesystem is clearly overloaded and under-resourced. We submitted complaints over 6months ago that have yet to be addressed.We submitted complaints over 12 monthsago that have been referred to other jurisdic-tions, about which we have heard no more;meanwhile, promotion continues.

ImplicationsIn 2003, the Expert Committee on Comple-mentary Medicines in the Health System wasestablished to reassure the public about thesafety and quality of CAMs. The Committeesaid (Finding 4.1.1) that the “Governmentneeds to take a more active role in ensuringthat consumers have access to reliable infor-mation about complementary medicines,and the skills to interpret information andmake informed decisions”.6 In 2005, thegovernment responded to the expert com-mittee report by accepting, noting or sup-po r t i ng a l l b u t on e o f th e 4 9recommendations. The TGA established theComplementary Medicines ImplementationReference Group to oversee the implementa-tion and has provided progress reports.18

Despite the widespread use of CAMs,many consumers are unaware that listedmedicines do not undergo the same strin-gent evaluation process as registered medi-cines, or indeed, that there is a differencebetween the two. Consumers are not suffi-ciently protected by regulation in this case. It

is difficult to reconcile the therapeutic claims made for manyCAMs with the objects of the Act: “to provide for . . . a nationalsystem of controls relating to the quality, safety, efficacy and timelyavailability of therapeutic goods…” (s. 4, our italics).

In an attempt to explain the difference, the TGA produced apamphlet in 1995 called Buying medicines — what’s on the label forme? It was available in pharmacies and health food shops and isnow on the Internet.19 While the content reflects the legalsituation, the omission that AUST L listed medicines are notevaluated for efficacy diminishes the utility of the pamphlet for the

4 Xantrax (Hershel-Beck Laboratories), an example of a listed weight-loss product

Ingredients

Each Xantrax tablet contains:

• Camellia sinensis (green tea)

• Citrus aurantium fruit (bitter orange)

• Paullinia cupana (guarana)

• Panax ginseng (Korean ginseng)

• Ilex paraguariensis (yerba mate)

• 11 additional vitamins and minerals

Therapeutic claims

Xantrax helps by:

• delaying gastric emptying thus prolonging a sense of fullness

• suppressing appetite

• maintaining healthy energy levels

• improving exercise performance

• enhancing the body’s ability to cope with stress

• supporting healthy metabolism

Pharmacy poster for Xantrax.

MJA • Volume 188 Number 1 • 7 January 2008 23


very people to whom it is directed. This has financial as well ashealth implications for consumers. Brian Grogan, national presi-dent of the Pharmaceutical Society of Australia, has noted:

While those products that lack evidence for effectiveness maynot actively harm the physical health of those who take them,they may well be harming patients’ financial health, some ofwhom may have to forgo other more beneficial evidence-basedtreatments or other necessities.20

In addition, any herb has many different chemical constituents,the presence and concentration of which vary, depending on thesource of the herb, and the extraction and standardisation methodsused. Marked variations of chemical constituents have been foundin different commercial products that purported to contain thesame amount of a particular herb.21 Currently, the TGA acceptscrude assays that do not necessarily confirm that one herbalproduct has the same chemical constituents as another that hasbeen proven to be clinically effective. In addition, the TGA doesnot require stability data on listed products.

Finally, the large number of repeated breaches of the AdvertisingCode by certain companies, together with an increasing backlog ofcomplaints, shows that complaint procedures are no substitute foradequate regulation at the time of market entry. Consumers (andhealth professionals) cannot exercise informed choice about CAMsif they are denied information about the quality and efficacy ofthese products.

Solutions

How could the present situation be improved? We propose thefollowing actions:• AUST L medicines (and homoeopathic medicines) shouldinclude on their labels a statement, such as “This medicine has notbeen evaluated by Australian health authorities for efficacy”.• A campaign to educate the public about such matters is needed.This would best be done by the National Prescribing Service,which is currently conducting a survey of educational needs inrelation to CAMs.• Ethical codes of conduct and complaint procedures for CAMs,over-the-counter and prescription drugs should be streamlined,harmonised and brought under one adequately resourced author-ity. Consistent (and meaningful) sanctions should be imposed oncompanies that repeatedly breach codes (for example, correctiveadvertising orders and fines linked to company turnover, with themoney used to support the complaint system).• The ARTG database should be updated with respect to listedproducts. Sponsors should be required to add key evidencesupporting each indication on the ARTG and entries should bechecked by staff of the regulatory body and coded with respect totherapeutic indication. This information should be publicly availa-ble on the Internet.• The TGA should check the analysis of herbal products morethoroughly and allow sponsors to use clinical trial evidencerelating to other products only where their own product has beenshown to have an identical herbal preparation, extraction andstandardisation process.• Finally, we believe that, in the longer term, the listing systemshould be scrapped, and CAMs (including homoeopathic medi-cines) should be assessed for efficacy and delisted if evidence islacking. Public money should be used for this, not listing fees.There is a current perception that 100% cost-recovery by the TGA

(as with the Food and Drug Administration in the United States)has led to commercial considerations outweighing the need forconsumer protection.22,23

Listed weight-loss products would be a good place to start theregulatory reform, given the increasing problem of obesity inAustralia.

AcknowledgementsWe are most grateful for the information provided by officers of theTherapeutic Goods Administration and the Therapeutic Goods AdvertisingCode Council.

Competing interestsNone identified.

Author detailsKen J Harvey, FRCPA, Adjunct Senior Research Fellow1

Viola S Korczak, BEc(SocSc), MIPH, Health Policy Officer2

Loretta J Marron, BSc, AssocDipBus3

David B Newgreen, BPharm, MBA4

1 School of Public Health, La Trobe University, Melbourne, VIC.2 Choice (Australian Consumers’ Association), Sydney, NSW.3 Brisbane, QLD4 Melbourne, VIC.Correspondence: [email protected]

References1 MacLennan AH, Myers SP, Taylor, AW. The continuing use of complemen-

tary and alternative medicine in South Australia: costs and beliefs in 2004.Med J Aust 2006; 184: 27-31.

2 CHOICE. Test: slimming pills. http://www.choice.com.au/viewArti-cle.aspx?id=105065&catId=100232&tid=100008 (accessed Nov 2007).

3 Therapeutic Goods Administration. The Therapeutic Goods Administra-tion’s risk management approach to the regulation of therapeutic goods.Version 1. Canberra: Department of Health and Ageing, 2004. http://tga.gov.au/about/tgariskmnt.pdf (accessed Nov 2007).

4 Therapeutic Goods Administration. Listed complementary medicines. In:Australian regulatory guidelines for complementary medicines part II(ARGCM). Canberra: Department of Health and Ageing, 2005. http://www.tga.gov.au/docs/html/argcm.htm#argcmp2 (accessed Nov 2007).

5 McEwen J. What does TGA approval of medicines mean? Aust Prescriber2004; 27: 156-158.

6 Expert Committee on Complementary Medicines in the Health System.Report to the Parliamentary Secretary to the Minister for Health andAgeing. Canberra: Commonwealth of Australia, 2003: 22, 115. http://www.tga.gov.au/docs/pdf/cmreport.pdf (accessed Nov 2007).

7 Therapeutic Goods Administration. Submission to the Productivity Com-mission Review of Cost Recovery by Commonwealth Agencies. Can-berra: Department of Health and Ageing, 2000. http://www.pc.gov.au/__data/assets/pdf_file/0019/39250/sub094.pdf (accessed Nov 2007).

8 Therapeutic Goods Administration. Summary of fees and charges at 1July 2007. Canberra: Department of Health and Ageing. http://www.tga.gov.au/fees/fees07.htm (accessed Nov 2007).

9 Therapeutic Goods Administration. Making a complaint about advertis-ing. Canberra: Department of Health and Ageing, 2007. http://www.tga.gov.au/docs/html/advcomplaint.htm (accessed Nov 2007).

10 Pyne C. Therapeutics products endorsements by doctors to be banned[media release]. Canberra: Department of Health and Ageing, 2007; 7Feb (CP08/07). http://www.health.gov.au/internet/ministers/publish-ing.nsf/content/mr-yr07-cp-pyn008.htm (accessed Nov 2007).

11 Ioannides-Demos LL, Proietto J, McNeill JJ. Pharmacotherapy for obes-ity. Drugs 2005; 65: 1391-1418.

12 Egger G, Cameron-Smith D, Stanton R. The effectiveness of popular,non-prescription weight loss supplements. Med J Aust 1999; 171: 604-608.

24 MJA • Volume 188 Number 1 • 7 January 2008

http://www.tga.gov.au/docs/pdf/cmreport.pdf

http://www.pc.gov.au/__data/assets/pdf_file/0019/39250/sub094.pdf


13 Pittler MH, Ernst E. Complementary therapies for reducing body weight:a systematic review. Int J Obes 2005; 29: 1030-1038.

14 Adverse Drug Reactions Advisory Committee. Adverse reactions tocomplementary medicines. Aust Adverse Drug React Bull 2005; 24: 1.http://www.tga.gov.au/adr/aadrb/aadr0502.htm (accessed Nov 2007).

15 Pittler MH, Schmidt K, Ernst E. Adverse events of herbal food supple-ments for body weight reduction: systematic review. Obes Rev 2005; 6:93-111.

16 Therapeutic Products Advertising Complaints. Complaints ResolutionPanel determination. Complaint 4-1106 Xantrax. Sydney: ComplaintsResolution Panel, 2007. http://www.tgacrp.com.au/index.cfm?pageID=13&special=complaint_single&complaintID=809 (accessed Nov 2007).

17 Therapeutic Products Advertising Complaints, Complaints ResolutionPanel. Complaints register. Sydney: Complaints Resolution Panel, 2007.http://www.tgacrp.com.au/index.cfm?pageID=13 (accessed Nov 2007).

18 Therapeutic Goods Administration. Implementation of the governmentresponse to the recommendations of the expert committee on comple-mentary medicine in the health system. Progress report. Canberra:

Department of Health and Ageing, 2006. http://www.tga.gov.au/cm/cmreport3.pdf (accessed Nov 2007).

19 Therapeutic Goods Administration. Buying medicines: what’s on thelabel for me? Canberra: Department of Health and Ageing, 2007. http://www.tga.gov.au/docs/html/buymed.htm (accessed Nov 2007).

20 Pharmaceutical Society of Australia. Check the evidence before pro-claiming a ‘miracle’ [media release]. Sydney: PSA, 2006. http://www.psa.org.au/site.php?id=235 (accessed Nov 2007).

21 Jiang B, Kronenberg F, Nuntanakorn P, et al. Evaluation of the botanicalauthenticity and phytochemical profile of black cohosh products by high-performance liquid chromatography with selected ion monitoring liquidchromatography-mass spectrometry. J Agric Food Chem 2006; 54: 3242-3253.

22 Kmietowicz Z. Repeal law that puts “FDA on the payroll of the industry”,says former NEJM editor. BMJ 2007; 334: 447. http://www.bmj.com/cgi/content/short/334/7591/447-a (accessed Nov 2007).

23 Hennessy S, Strom BL. PDUFA reauthorization — drug safety’s goldenmoment of opportunity? N Engl J Med 2007; 356: 1703-1704.

(Received 3 May 2007, accepted 31 Oct 2007) ❏

MJA • Volume 188 Number 1 • 7 January 2008 25

OR I G I N A L A R T I C L E

Efficacy of a novel herbal formulation for weight lossdemonstrated in a 16-week randomized, double-blind,placebo-controlled clinical trial with healthy overweight adults

Kashinath Dixit MD1 | Dinesh V. Kamath MD2 | Krishnaraju V. Alluri MS3 |

Barbara A. Davis PhD4

1Krupa Centre for Diabetes and Obesity,

Bengaluru, India

2Sudeep Diabetes Care Centre, Bengaluru,

India

3Laila Nutraceuticals R&D Center, Vijayawada,

India

4PLT Health Solutions Inc., Morristown, New

Jersey

Correspondence

Barbara A. Davis, PhD, PLT Health Solutions

Inc., 119 Headquarters Plaza, Morristown, NJ

07960.

Email: [email protected]

Funding information

This study was funded by Laila Nutraceuticals,

India and PLT Health Solutions Inc. (grant

number C007185).

Aim: To re-evaluate the weight loss efficacy of LI85008F in healthy overweight adults via a

16-week randomized, double-blind, placebo-controlled clinical study.

Materials and Methods: One hundred and forty overweight participants (body mass index [BMI]

27-29.9 kg/m2, 29.3% male; ages 21-50 years) were randomized into placebo (n =70) and

LI85008F (n =70) groups. The participants received either 900 mg/d of LI85008F in two divided

doses or two identical placebo capsules. In addition, participants were counselled to follow an

~1800 kcal/d diet and to engage in walking for 30 min, 5 d/wk throughout the study.

Results: At the end of the trial period, the LI85008F supplemented group showed significant

reductions in body weight (5.36 � 1.769 vs. 0.87 � 1.381 kg; P < 0.0001) and BMI

(2.05 � 0.693 vs. 0.34 � 0.559 kg/m2; P < 0.0001), compared with placebo. Significant reduc-

tions in waist and hip circumferences, and a 2.08-fold reduction of waist/hip ratio, were noted

in the LI85008F supplemented group. LI85008F supplementation also resulted in significant

improvements in lipid profiles, compared with the placebo; low-density lipoprotein (LDL) choles-

terol decreased, while high-density lipoprotein (HDL) cholesterol increased, resulting in a signifi-

cantly improved LDL/HDL ratio. No major adverse events were reported by the participants

during the study.

Conclusions: The unique herbal extract blend LI85008F, combined with modest calorie restric-

tion and physical activity, is well tolerated, safe, and effective for weight management in over-

weight men and women.

KEYWORDS

body mass index, body weight management, Curcuma longa, LI85008F, Moringa oleifera,

Murraya koeingii, randomized double-blind placebo-controlled clinical study

1 | INTRODUCTION

An estimated 1 billion adults are overweight and at least 300 million

are obese worldwide, with prevalence increasing in most countries.1,2

Body mass index (BMI) is an established measure for classifying

weight, and is often used as a surrogate for total body fat.3 Over-

weight and obesity, classified by a BMI of 25-29.9 and ≥30 kg/m2,

respectively, have been associated with increased risk of comorbid-

ities such as type 2 diabetes, cardiovascular disease, osteoarthritis,

and some cancers.4

Alternative strategies for body weight management have become

widely adopted because of the high cost and potentially adverse

effects of conventional pharmaceutical and/or surgical interventions.

Among those approaches, nutritional ingredients such as botanicals

are popular for the management of overweight and obesity.5

The herbal combination, LI85008F, was developed to meet the

need for high quality, clinically evaluated botanical body weight man-

agement dietary ingredients. An in vitro screening programme, estab-

lished by Laila Nutraceuticals (Vijayawada, India), evaluated hundreds

of herbal extracts for their ability to inhibit fat accumulation by

Received: 8 April 2018 Revised: 15 June 2018 Accepted: 16 June 2018

DOI: 10.1111/dom.13443

Diabetes Obes Metab. 2018;1–9. wileyonlinelibrary.com/journal/dom © 2018 John Wiley & Sons Ltd 1

http://orcid.org/0000-0002-5379-943X

mailto:[email protected]

http://wileyonlinelibrary.com/journal/dom

adipocyte differentiation (i.e. adipogenesis) and potentiate fat break-

down within cells (i.e. lipolysis) in 3T3-L1 mouse adipocytes.6 The

three extracts shown to be most effective in this screening were com-

bined in various ratios, with the most effective synergistic combina-

tion being LI85008F. The resulting dietary ingredient inhibits

lipogenesis in adipocytes while concurrently antagonizing PPARγ and

other lipogenic factors. In addition, it potentiates triglyceride mobiliza-

tion from fat cells, that is, enhances lipolysis.6

Supplementation of LI85008F in obese adults in an 8-week

double-blind placebo-controlled clinical study resulted in significant

reductions in body weight and BMI along with improvements in serum

lipid profiles and a significant increase in serum adiponectin. Observa-

tions relevant to safety parameters supported that LI85008F was well

tolerated and safe.7 A comprehensive set of in vitro and in vivo toxi-

cological studies also support the safety of LI85008F.8

The clinical efficacy and safety profile of LI85008F prompted fur-

ther evaluation in a larger population of overweight participants over

a longer duration. This paper presents the clinical efficacy and tolera-

bility of LI85008F in healthy overweight participants (BMI

27-29.9 kg/m2) in a 16-week double-blind placebo-controlled study.

2 | MATERIALS AND METHODS

2.1 | Study material

The herbal formulation LI85008F was prepared in the ratio of six parts

Moringa oleifera leaf aqueous ethanol extract, three parts Murraya koe-

nigii (L.) Spreng. (family Rutaceae) leaf aqueous ethanol extract, and

1 part Curcuma longa L. (family Zingiberaceae) extract standardized to

not less than 95% total curcuminoids. Identification, collection of the

plant raw materials, and the extraction procedures of the individual

ingredients from the respective raw materials were described previ-

ously.6,7 The finished formulation was standardized to contain at least

7.0% total curcuminoids, 0.1% Mahanine and 0.2% Quercetin 3-O-

glycoside. LI85008F was produced in a cGMP-certified manufacturing

facility at Laila Nutraceuticals. This formulation is available commer-

cially as Slimvance/Slendacor through PLT Health Solutions Inc.

(Morristown, NJ).

A typical high-performance liquid chromatography (HPLC) chro-

matogram of this ingredient is presented in Figure 1. LI85008F was

solubilized and diluted in 0.1% orthophosphoric acid: methanol

(20:80) and analysed using a HPLC system connected to a PDA detec-

tor equipped with Empower3 software (Waters, Milford, MA). The

sample was applied onto an X Bridge C18 column (100 × 4.6 mm,

3.5 μm) (Waters) through a 10-μL auto injector. The mobile phase

consisted of a gradient of 0.1% orthophosphoric acid: acetonitrile.

The run was conducted at 30�C for 32 min and the eluted samples

were analysed at 254 nm. Analysis of the final formulation

(i.e. LI85008F) was carried out in the analytical department of Laila

Nutraceuticals. In addition, possible contaminants such as microbes

and heavy metals were also analysed.

The dose of LI85008F (900 mg/d) in the clinical study was chosen

based on a preclinical proof of concept study conducted in high-fat

diet-induced obese rats (unpublished observation). For clinical study,

LI85008F was encapsulated in size zero hard gelatin capsules; the pla-

cebo capsules contained 99.56% maize starch and 0.44% syloid. The

capsules containing LI85008F or placebo were practically indistin-

guishable, being identical in size, weight, and external appearance

such as colour and texture. At each visit, all study product was col-

lected, and unused capsules were counted to determine compliance.

Missed doses were captured in the Daily Diary and Compliance Card,

and in the respective case report forms (CRFs).

2.2 | Study objectives and outcomes

The purpose of the current clinical investigation was to evaluate the

body weight loss efficacy and tolerability of LI85008F in healthy over-

weight participants. The primary outcome at the end of treatment

period was change in body weight from baseline. Secondary outcome

measures included reduction in BMI, waist and hip circumferences,

changes in body composition (reduced fat mass), serum lipid, adipo-

nectin, and ghrelin profiles. Vital signs, ECG, clinical chemistry, haema-

tology, and reported adverse events were considered as parameters

to evaluate the safety and tolerability.

2.3 | Screening and recruitment

The clinical study protocol was reviewed and approved by an ethics

committee (Bangalore Ethics, Bengaluru, India); the approved protocol

was registered (Clinical Trial Registry-India/2015/06/005835). The

study was conducted in accordance with the ethical principles of the

Declaration of Helsinki and was consistent with Good Clinical Practice

and the applicable regulatory requirements. The study took place from

June 1 to November 15, 2015 and was conducted at two independent

centres, Sudeep Diabetes Care Centre, Bengaluru, and Krupa Centre

for Diabetes and Obesity, Bengaluru. These two sites were monitored

by an independent site monitoring organization (SMO). An indepen-

dent third-party auditor audited technical and regulatory aspects of

the study. The CRFs were audited for compliance to source data, and

the trial master file was reviewed for regulatory compliance.

Participants visiting the outpatient departments of the clinics

were selected for screening. After voluntarily signing informed con-

sent, male and female participants were screened for eligibility for

enrollment into the study based on the inclusion and exclusion cri-

teria, as previously described7 but with some modifications. Briefly,

criteria for eligibility required that participants be aged 21-50 years,

have a BMI 27-29.9 kg/m2, have an apparently healthy status based

on their medical history, be free from metabolic bone disease, gastro-

intestinal disease, diabetes mellitus (type 1 or 2), cardiovascular dis-

ease, renal disease and abnormal liver function, on no medications or

vitamin supplements, and not pregnant or lactating. Individuals with

HIV, inflammatory disorders, unexplained weight loss or gain within

the last 3 months, following weight-loss programmes, taking weight-

loss drugs, and those smoking or drinking alcohol, were excluded. Of

the 157 participants screened, 140 met the above inclusion criteria

and were recruited for the study.

2 DIXIT ET AL.

2.4 | Study design

Participant disposition throughout the study is presented in the Con-

solidated Standards of Reporting Trials (CONSORT) flow diagram

(Figure 2).9 Participants (n = 140) were randomized into two groups

using a computer-generated block randomization method (http://

www.randomization.com) by an independent statistician, which

included the LI85008F and placebo groups (n = 70/group). The study

investigators were blinded to allocation. The eligible participants were

FIGURE 1 A typical high-performance liquid chromatography (HPLC) chromatogram, showing the major components of LI85008F. Total

curcuminoids, Mahanine and Quercetin 3-O-glycoside have been identified at 254 nm. The results are plotted in arbitrary units (AU) versuselution time (min)

CONSORT 2010 Flow Diagram

Enrollment Assessed for eligibility (n= 157)

Excluded (n= 17)

♦ Not meeting inclusion criteria (n= 09) ♦ Declined to participate (n= 08) ♦ Other reasons (n= 00)

Randomized (n= 140)

Allocation Allocated to Placebo (n= 70)♦ Received allocated intervention (n= 70) ♦ Did not receive allocated intervention

(give reasons) (n= 00)

Allocated to Treatment (n= 70)♦ Received allocated intervention (n= 70) ♦ Did not receive allocated intervention

(give reasons) (n= 00)

Lost to follow-up (give reasons) (n= 00)

Discontinued intervention (Subject’s decision to discontinue) (n= 06)

Follow-Up

Lost to follow-up (give reasons) (n= 00)

Discontinued intervention (Subject’s decision to discontinue) (n= 04)

Analysis

Analysed (n=64)

♦ Excluded from analysis (give reasons) (n= 0)

Analysed (n=66)

♦ Excluded from analysis (give reasons) (n= 0)

FIGURE 2 CONSORT flow diagram of subject disposition. Eligible subjects (n = 140) were randomized into LI85008F or placebo groups. Final

analysis was conducted on the per-protocol population

DIXIT ET AL. 3

http://www.randomization.com

http://www.randomization.com

randomized as per the randomization codes labelled on the investiga-

tional product in a 1:1 ratio. Study capsules, compliance card, list of

instructions and dates of follow-up evaluations were provided to all

participants at the baseline visit. Each active and placebo capsule con-

tained 450 mg of LI85008F or 450 mg of excipients, respectively.

Participants in both groups were instructed to take two capsules per

day; one before breakfast and one before dinner. They were also

advised to walk for 30 min, 5 d/wk, and to maintain a diet of

~1800 kcal/d as instructed by the principal investigator and a dieti-

tian. A study dietitian shared daily menus with each subject, and pro-

vided counselling to assist participants in maintaining the standard

diet during the study. The diary cards containing information about

compliance with the study's supplement, diet and exercise were

reviewed at each follow-up visit. Study supplement compliance

was ≥80%.

The intervention was conducted for 16 weeks, which included

baseline and follow-up visits at 2, 4, 8, 12 and 16 weeks. At all visits,

participants were assessed for anthropometric parameters including

body weight, height, waist circumference, hip circumference, along

with vital signs. Participants also completed the Profile of Mood

States - Short Form (POMS-SF) questionnaire. The primary efficacy

parameter, body weight, was measured using an electronic weighing

scale (Aliston AL650 Weighing Scale, Mumbai, India) at all study visits.

Body fat assessment was carried out at baseline (visit 2) and week

16 (visit 7) through dual-energy X-ray absorptiometry (DEXA)

(encore-based X-ray Bone Densitometer; Lunar Prodigy Series, GE

Medical Systems).

A copy of the protocol is available upon request to PLT Health

Solutions Inc. (NJ).

2.5 | Haematological and biochemical evaluations

For the assessment of LI85008F safety, several parameters were eval-

uated in serum, urine and whole blood of all participants at the base-

line and final visits. Serum lipids were also evaluated. Biochemical and

haematological parameters were measured using the COBAS

INTEGRA (400 PLUS) auto-clinical chemistry analyzer (Roche Diag-

nostics, Rotkreuz, Switzerland) and the Mindray BC-5380 auto-

haematology analyzer (Shenzhen, China), respectively. Urine analysis

was carried out using UroColor Strips (Standard Diagnostics, Kyonggi-

do, Korea) and by microscopy of sediment.

2.6 | Serum biomarkers

Serum adiponectin and ghrelin levels were determined by specific EIA

methods using human enzyme-linked immunosorbent assay (ELISA)

kits procured from R&D Systems (Minneapolis, MN) and RayBiotech

(Norcross, GA), respectively, according to the instructions provided by

the manufacturers.

2.7 | Statistical analysis

Descriptive statistics are presented as mean � SD. All outcome mea-

sures (i.e. primary and secondary endpoints) in the per-protocol popu-

lation were analysed by parametric tests including paired t-test and

unpaired t-test, to compare means within and between the groups.

Comparison between body weights at the follow-up visits between

the LI85008F and placebo groups were analysed using Analysis of

Covariance (ANCOVA).

ANCOVA was used to compare inter- and intra-group reduction

of body weight from baseline to the final visit (i.e. at 16 weeks)

between the LI85008F and placebo groups. The interaction between

the groups over time was evaluated by ANCOVA with the statistical

significance level set at P ≤ 0.05.

Group size estimations were based on power calculations, pre-

dicting the effect size and variations between and within groups. The

effect and deviation sizes observed in the previous clinical study7 con-

ducted in obese participants were 1.79 and 1.52 in the placebo, and

4.76 and 2.3 in the LI85008F groups, respectively. As the current

study was conducted in healthy overweight participants, a lower

effect size was considered. The assumed effect and deviation sizes,

1.4 and 1.8 in the placebo, and 3.0 and 2.8 in the treatment groups,

with sample sizes of 60 per arm, were sufficient to achieve a power of

>90%. In this study population, it was anticipated that there could be

at least a 5% reduction of the baseline body weight in the LI85008F

group at the end of the study; a 15% dropout rate was estimated. Tak-

ing into account these assumptions, 60 completers per cohort was

sufficient to achieve ≥90% power to detect outcome differences of

changes in body weight between the groups, assuming a two-sided

significance level of 0.05.

3 | RESULTS

3.1 | Demographic and baseline characteristics

The demographic and baseline characteristics are summarized in

Table 1. Participants were randomly distributed into placebo and

treatment groups. Overall, the active group receiving LI85008F

(900 mg/d, n = 70) and placebo (n = 70) were not statistically differ-

ent at baseline with respect to any characteristic measured.

TABLE 1 Demographic and baseline characteristics of the LI85008F

and placebo groups

CharacteristicLI85008F(n = 70)

Placebo(n = 70)

Pvalue*

Gender

Men (%) 26 (44.8) 32 (55.17) -

Women (%) 44 (53.66) 38 (46.34) -

Age (years.) 35.16 � 9.296 37.26 � 9.756 0.194

Body weight (kg) 75.73 � 9.710 75.11 � 10.295 0.714

Height (cm) 162.03 � 9.347 162.19 � 9.555 0.920

BMI (kg/m2) 28.71 � 0.894 28.41 � 1.048 0.070

Waistcircumference(cm)

98.64 � 9.928 97.86 � 7.980 0.609

Hip circumference(cm)

107.41 � 10.628 105.41 � 8.511 0.221

Waist : hip ratio 0.92 � 0.086 0.93 � 0.076 0.468

Values represent mean � SD.

*Two-tailed unpaired t-test between LI85008F and placebo.

4 DIXIT ET AL.

3.2 | Clinical efficacy

3.2.1 | Changes in anthropometric measures

Changes from baseline body weight, BMI, waist and hip circumfer-

ences in both groups are summarized in Table 2. LI85008F supplemen-

tation for 16 weeks resulted in statistically significant body weight

reduction versus placebo (5.36 � 1.769 kg vs. 0.87 � 1.381 kg;

P < 0.0001). Significant reduction in body weight was observed as

early as at 2 weeks in supplemented participants when compared with

the placebo (0.67 � 0.365 kg vs. 0.19 � 0.305 kg; P < 0.0001). Aver-

age baseline body weight loss in the LI85008F-supplemented group

was 7.08% whereas the placebo group lost only 1.16% of the baseline

body weight (Table 2, Figure 3). LI85008F supplementation for

16 weeks also showed significant reduction of BMI from baseline ver-

sus placebo (2.05 � 0.693 vs. 0.34 � 0.559; P < 0.0001) (Table 2).

This statistically significant BMI reduction in the LI85008F-

supplemented group also began as early as at 2 weeks (0.25 � 0.125

vs. 0.07 � 0.125; P < 0.0001). Furthermore, at the end of the trial

period, LI85008F supplementation resulted in significant reductions in

waist (5.38 � 1.602 vs. 1.70 � 1.827 cm; P < 0.0001) and hip

(4.49 � 1.664 vs. 1.19 � 1.465 cm; P < 0.0001) circumferences when

compared with the placebo. The mean reduction of waist/hip ratio in

the LI85008F group was 2.08-fold compared with the placebo

TABLE 2 Reductions in anthropometric variables in the LI85008F and placebo groups from the baseline through to week 16

Parameter WeekLI85008F(n = 66)

Placebo(n = 64) P value*

Body weight (kg) 2 0.67 � 0.365 0.19 � 0.305 <0.0001

4 1.69 � 0.714 0.27 � 0.421 <0.0001

8 2.77 � 0.957 0.48 � 0.609 <0.0001

12 4.03 � 1.299 0.67 � 1.105 <0.0001

16 5.36 � 1.769 0.87 � 1.381 <0.0001

BMI (kg/m2) 2 0.25 � 0.125 0.07 � 0.125 <0.0001

4 0.64 � 0.257 0.10 � 0.171 <0.0001

8 1.06 � 0.359 0.19 � 0.245 <0.0001

12 1.54 � 0.503 0.26 � 0.450 <0.0001

16 2.05 � 0.693 0.34 � 0.559 <0.0001

Waist circumference (cm) 2 1.32 � 0.729 0.22 � 0.851 <0.0001

4 2.52 � 0.938 0.43 � 0.930 <0.0001

8 3.44 � 1.181 0.78 � 1.302 <0.0001

12 4.35 � 1.316 1.14 � 1.473 <0.0001

16 5.38 � 1.602 1.70 � 1.827 <0.0001

Hip circumference (cm) 2 1.43 � 0.837 0.31 � 0.986 <0.0001

4 2.73 � 1.322 0.45 � 1.127 <0.0001

8 3.28 � 1.465 0.67 � 1.251 <0.0001

12 3.82 � 1.590 0.86 � 1.492 <0.0001

16 4.49 � 1.664 1.19 � 1.465 <0.0001

Waist/hip ratio 2 0.00005 � 0.008 −0.00064 � 0.010 0.6805

4 0.0003 � 0.013 0.0003 � 0.012 0.9930

8 0.0043 � 0.014 0.0015 � 0.014 0.2574

12 0.00833 � 0.017 0.0034 � 0.015 0.0829

16 0.0123 � 0.020 0.0059 � 0.017 0.0547

Values represent mean � SD. Negative (−) values indicate increase in measures.

*The comparisons between changes in placebo and treatment groups were analysed using unpaired t-test.

FIGURE 3 Scatter diagram presents reduction of the baseline body

weight of the individual participants in the LI85008F-supplementedand placebo groups at week 16

DIXIT ET AL. 5

(0.0123 � 0.020 vs. 0.0059 � 0.017; P = 0.0547) (Table 2). Subgroup

analyses showed similar, statistically significant improvements in

anthropometric measures for male and female participants (data not

shown).

As a secondary outcome measure, body composition using DEXA

was also evaluated. At the end of the trial period, the LI85008F-

supplemented group had a reduction of 1.11 � 7.059 kg body fat,

whereas participants in the placebo group gained 0.61 � 5.052 kg

body fat from baseline (P = 0.1151) (Table 3). There was a statistically

significant difference (P = 0.0061) between mean change from base-

line lean mass between the LI85008F-supplemented versus the pla-

cebo group: whereas lean mass was increased (0.9 � 3.743 kg) in the

supplemented group, lean mass was lost in the placebo group

(−0.91 � 3.621 kg) (Table 3).

3.2.2 | Improvement in serum lipid profile

At the end of the 16-week trial period, the herbal supplementation

significantly decreased baseline serum low-density lipoprotein (LDL)

(30.20 � 18.387 vs. 1.08 � 9.519 mg/dL; P < 0.0001), very low-

density lipoprotein (VLDL) (6.80 � 6.369 vs. 1.09 � 3.059 mg/dL;

P < 0.0001), total cholesterol (28.04 � 21.805

vs. 5.37 � 10.203 mg/dL; P < 0.0001) and triglyceride

(34.12 � 31.682 vs. 5.09 � 14.99 mg/dL; P < 0.0001) compared with

the placebo group (Table 4). Significant reductions in LDL

(P < 0.0001), VLDL (P < 0.0001), total cholesterol (P < 0.0001) and

triglyceride (P < 0.0001) were observed as early as at 4 weeks. Fur-

thermore, at the end of the study, the LI85008F group also showed

significant improvement (P < 0.0001) in serum high-density lipopro-

tein (HDL) level by 8.66 � 8.908 mg/dL, whereas in the placebo

group, HDL level decreased by 3.51 � 5.543 mg/dL from the baseline

(Table 4).

3.2.3 | Modulation of adiponectin and ghrelin levels inserum

At the end of the study, LI85008F supplementation resulted in a

34.77% (P = 0.0071) increase in serum adiponectin concentration

from the baseline (4.279 � 2.105 vs. 3.175 � 1.772 μg/mL), whereas

the placebo group showed a 15.05% increase (P = 0.1127) in adipo-

nectin level from the baseline (Figure 4A). The LI85008F group

showed a 20.17% (P = 0.0568) reduction of serum ghrelin levels from

the baseline (97.15 � 35.42 vs. 121.7 � 92.74 ng/mL); in compari-

son, the placebo group showed a slight reduction of 10.42%

(110.46 � 47.99 vs. 123.31 � 91.48 ng/mL; P = 0.1945) (Figure 4B).

3.2.4 | Profile of mood states

Overall mood, assessed through the POMS-SF questionnaires, signifi-

cantly improved in the LI85008F group (P = 0.0021) (data not shown).

3.2.5 | Adverse events and dropouts

No serious adverse events were observed in this study. Minor events

reported by some participants included fever, gastritis, headache, itch-

ing, loose stool, acidity, increased appetite and dehydration. These

minor adverse events were evenly distributed among the two groups

and were probably not related to the study supplement.

Four participants from the LI85008F group and six participants

from the placebo group were excluded because of their non-

availability during the entire study duration; they were dropped from

the study prior to the outcome measure assessments. Therefore, the

number of completers were LI85008F (n = 66) and placebo (n = 64).

However, no subject was dropped from the study because of an

adverse event.

4 | DISCUSSION

Obesity and overweight continue to negatively impact society, over-

whelming health and healthcare services globally. Despite a real need,

relatively few botanical options that are supported by rigorous scien-

tific research exist to support body weight management.10 The cur-

rent study shows that a 16-week supplementation of a novel herbal

formula (LI85008F) reduces body weight, BMI, body fat, waist and hip

circumference, and waist/hip ratio in overweight participants with an

average BMI of 28.56 kg/m2. In addition, biochemical, haematological

parameters and subject compliance show that LI85008F is tolerable

and safe for human consumption. Previously, LI85008F was shown to

be a clinically effective and safe herbal composition for body weight

management in obese participants.7

The earlier, 8-week double-blind, placebo-controlled clinical

study, conducted on a smaller group (n = 41) of obese participants

(BMI 30-40 kg/m2) showed that LI85008F significantly reduced the

baseline body weight and BMI as well as maintaining healthy serum

lipid profiles.7 Demonstrating the mechanism of action of LI85008F at

the cellular level, another study showed that this novel composition,

made from three herbal extracts, synergistically reduced adipogenesis

and increased intracellular fat lysis processes in 3T3-L1 adipocytes

through a PPARγ-dependent pathway.6

TABLE 3 Comparison of body composition estimated by DEXA

VariableLI85008F(N = 65)

Placebo(N = 64)

Pvaluea

Fat mass

Baseline (kg) 33.17 � 9.567 30.60 � 7.895 0.0986

Week 16 (kg) 32.06 � 9.379 31.20 � 8.202 0.5827

Mean change inbaseline fat mass(kg)

−1.11 � 7.059 0.61 � 5.052 0.1151

P valueb 0.2098 0.3395

Lean mass

Baseline (kg) 41.26 � 7.773 41.37 � 8.137 0.9382

Week 16 (kg) 42.16 � 8.714 40.46 � 7.453 0.2363

Mean change inbaseline lean mass(kg)

0.90 � 3.743 −0.91 � 3.621 0.0061*

P valueb 0.0570 0.0490*

Values indicate mean � SD. Negative (−) values indicate loss of or reduc-tion in tissue mass. P valuea: unpaired t-test between the groups; P valueb:paired t-test between baseline and the end of intervention.

*Indicates significance (P < 0.05).

6 DIXIT ET AL.

The primary outcome of the current study was reduction of base-

line body weight in the active cohort. Body weight reductions of >5%

have been associated with improvements in metabolic and cardiovas-

cular health.11 Data from the current study show that an average of

7.08% of the baseline body weight was lost in the LI85008F group

after 16 weeks of intervention. Further analysis reveals that 54 out of

66 participants in the active group lost more than 5% of their baseline

body weight at the end of the trial (Figure 3). In addition, LI85008F

supplementation showed a series of compelling changes in the base-

line anthropometric measures of the study participants. Reductions

from baseline BMI of the LI85008F group versus the placebo group

were highly significant throughout the study and began as early as

week 2. This clinical efficacy of LI85008F is consistent with an earlier

study conducted with obese participants.7

BMI is considered as a marker of global adiposity, and is also a

reliable marker of visceral adiposity, as explained by the fact that vis-

ceral adipose tissue increases in a quasi-linear manner with BMI in

both sexes.12 Waist circumference (WC) and waist-hip ratio (WHR)

are commonly used as surrogate markers of visceral adiposity.13 Vis-

ceral obesity is a significant risk factor for cardiovascular morbidity

and mortality; therefore, increased WC is considered as one of the

vital diagnostic criteria for metabolic syndrome.13,14 In the current

TABLE 4 Changes in serum fat metabolism markers in the LI85008F and placebo groups from baseline

Parameter WeekLI85008F(n = 66)

Placebo(n = 64) P value*

HDL (mg/dL) 4 2.57 � 6.173 0.25 � 6.402 0.0375

8 5.23 � 7.460 −2.02 � 6.903 <0.0001

16 8.66 � 8.908 −3.51 � 5.543 <0.0001

LDL (mg/dL) 4 −12.52 � 12.229 1.59 � 12.261 <0.0001

8 −23.53 � 17.700 0.63 � 13.151 <0.0001

16 −30.20 � 18.387 −1.08 � 9.519 <0.0001

VLDL (mg/dL) 4 −2.80 � 4.558 −0.06 � 3.399 0.0002

8 −4.67 � 5.079 −0.78 � 3.722 <0.0001

16 −6.80 � 6.369 −1.09 � 3.059 <0.0001

Total cholesterol (mg/dL) 4 −12.35 � 14.650 2.04 � 12.632 <0.0001

8 −22.57 � 20.248 −1.81 � 14.957 <0.0001

16 −28.04 � 21.805 −5.37 � 10.203 <0.0001

Triglycerides (mg/dL) 4 −15.06 � 19.796 0.02 � 16.559 <0.0001

8 −23.18 � 25.364 −3.17 � 18.306 <0.0001

16 −34.12 � 31.682 −5.09 � 14.990 <0.0001

LDL/HDL ratio 4 −0.31 � 0.361 0.02 � 0.401 <0.0001

8 −0.59 � 0.423 0.09 � 0.399 <0.0001

16 −0.78 � 0.460 0.12 � 0.352 <0.0001

HDL, high-density lipoprotein; LDL, low-density lipoprotein; VLDL, very low-density lipoprotein. Negative (−) and positive values indicate decreases andincreases in measures, respectively. Values represent mean � SD.

*Comparisons between changes in placebo and treatment groups were analysed using unpaired t-test.

FIGURE 4 LI85008F modulates adiponectin and ghrelin levels in serum. In panel A, each bar represents the serum adiponectin concentration

(mean � SD) of participants supplemented with LI85008F and placebo at the baseline and at week 16, respectively. In panel B, each barrepresents the serum ghrelin concentration (mean � SD) of participants supplemented with LI85008F and placebo at the baseline and at week16, respectively. LI85008F (n = 44) and placebo (n = 55). Paired t-test was performed for intra-group comparison between baseline and week 16;* indicates significance at <0.05

DIXIT ET AL. 7

study, LI85008F supplementation conferred significant reduction of

WC and a reduction in WHR (P = 0.0547) compared with the placebo.

The LI85008F group experienced a significant reduction from baseline

WC as early as at 2 weeks compared with the placebo group. The

reduction of visceral adiposity in the LI85008F group is supported by

the observation of a significant reduction of 1.20% total body fat

achieved at the end of the study. Together, these data suggest that

LI85008F is an effective option for reducing body weight and fat in

overweight participants.

LI85008F-supplemented participants experienced significant

improvements in serum markers of lipid metabolism related to over-

weight and obesity. Hyperlipidaemia is generally associated with over-

weight and obesity, which is a known risk factor for cardiovascular

disease including atherosclerosis.15,16 The study showed reductions in

serum LDL, VLDL, total cholesterol, triglyceride, and LDL/HDL ratio

following a similar pattern to weight loss over the 16-week trial

period, with significant effects noticed as early as at 4 weeks. Con-

comitantly, serum HDL level was also significantly improved in the

LI85008F group. The reduced level of harmful lipids in circulation

(i.e. LDL triglycerides and the LDL/HDL ratio) reflected an improved

status of fat metabolism and reduced stored fat in the body. Overall,

the improvements in serum lipid profile in the LI85008F-

supplemented participants implies possible cardiovascular benefits for

overweight participants.

In the study, there was a slightly greater percentage of female

than male participants. Among the 130 completers, 75 were female

(40 participants in the LI85008F group and 35 participants in the pla-

cebo group). A chi square test (P = 0.4947) suggested that there was

no association between gender variation and treatment effect.

This study, together with the previous investigation,7 shows

weight loss efficacy across a range of adult ages, in both genders, and

in overweight as well as obese individuals. The fact that not only body

weight, but BMI, WC, hip circumference, WHR, and fat mass via

DEXA were positively modified by LI85008F suggests consistent effi-

cacy across multiple parameters related to body weight management.

Additional research into whether race and ethnicity play a role in effi-

cacy may be warranted. However, whereas differences in visceral adi-

posity at various BMIs has been noted across different ethnic

backgrounds,17 this may be more relevant to health outcomes associ-

ated with BMI rather than the efficacy of a weight management

ingredient.

A notable limitation of the study is the lack of food intake data.

Whereas participants in both groups were provided with regular

counselling and example menu plans by a study dietitian, dietary

intake was not monitored. Accuracy and reliability of food intake

assessments is complex, often requiring multiple assessment tools to

provide a true representation of food consumption.18 In a long-term

study such as this 16-week intervention trial, the duration placed a

burden on study participants, especially when the primary outcome

measure was to evaluate efficacy of the dietary ingredient. Partici-

pants were required to complete compliance cards daily, and analysis

showed no significant difference in diet-compliant days between the

placebo and treatment groups (data not shown). However, future

research could include a design that allows investigation of the impact

of dietary intake in conjunction with LI85008F intake.

Together with previous work, the current investigation has estab-

lished that LI85008F is well-tolerated, safe and effective. The individ-

ual ingredients of LI85008F have a very long history of use in the

cuisine of Indian and other cultures. Moreover, a preclinical safety

study and a clinical study on obese participants had previously estab-

lished that LI85008F was safe and tolerable for human use.8,7 Simi-

larly, in the current study, no major adverse events were reported by

the participants. The current research demonstrates that this unique

herbal extract blend LI85008F, combined with modest calorie restric-

tion and physical activity, is effective for body weight management in

overweight men and women.

ACKNOWLEDGMENTS

The authors thank Sri. G. Ganga Raju, Chairman, Mr. G. Rama Raju,

Director, Laila Group, and Mr. B. Kiran, CEO, Laila Nutraceuticals, for

encouragement and generous support. In addition, the authors are

grateful to Paul Flowerman, Chairman, and Seth Flowerman, President

of PLT Health Solutions, for their support.

Conflict of interest

K. D. and D. V. K. are employees of the Krupa Centre for Diabetes

and Obesity and Sudeep Diabetes Care Centre, Bengaluru, India. K. V.

A. is an employee of Laila Nutraceuticals, India. B. A. D. is an employee

of PLT Health Solutions Inc., NJ. This study was funded by Laila

Nutraceuticals, India and PLT Health Solutions Inc. (grant number

C007185); K. D. and D. V. K. were the grant recipients.

Author contributions

The authors' responsibilities were as follows. K. V. A. and B. A.

D. designed the research; K. D. and D. V. K. conducted the research;

Laila Nutraceuticals, under the direction of K. V. A., produced the

intervention products; all the authors analysed and interpreted the

data; K. V. A. and B. A. D. wrote the manuscript; B. A. D. had primary

responsibility for the final content; and all the authors read and

approved the final manuscript.

ORCID

Barbara A. Davis http://orcid.org/0000-0002-5379-943X

REFERENCES

1. Ogden CL, Yanovski SZ, Carroll MD, Flegal KM. The epidemiology ofobesity. Gastroenterology. 2007;132:2087-2102.

2. World Health Organization. Obesity and Overweight. Geneva, Switzer-land; 2014. http://www.who.int/mediacentre/factsheets/fs311/en/.Accessed December 01, 2017.

3. Food and Drug Administration (FDA). Guidance for Industry DevelopingProducts for Weight Management, I:\7544dft.doc; 2007. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm071612.pdf. Accessed October 24, 2017.

4. Whitlock G, Lewington S, Sherliker P, et al. Body-mass index andcause-specific mortality in 900000 adults: collaborative analyses of57 prospective studies. Lancet. 2009;373:1083-1096.

5. Allison DB, Fontaine KR, Heshka S, Mentore JL, Heymsfield SB. Alter-native treatments for weight loss: a critical review. Crit Rev Food SciNutr. 2001;41:1-28.

8 DIXIT ET AL.

http://orcid.org/0000-0002-5379-943X

http://orcid.org/0000-0002-5379-943X

http://www.who.int/mediacentre/factsheets/fs311/en/

http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm071612.pdf



6. Sengupta K, Golakoti T, Chirravuri VR, Marasetti AK. An herbal for-mula LI85008F inhibits lipogenesis in 3T3-L1 adipocytes. Food NutrSci. 2011;2:809-817.

7. Sengupta K, Mishra AT, Rao MK, Sarma KVS, Krishnaraju AV,Trimurtulu G. Efficacy and tolerability of a novel herbal formulationfor weight management in obese subjects: a randomizeddouble-blind placebo controlled clinical study. Lipids Health Dis.2012;11:122.

8. Alluri KV, Sundararaju D, Srinivas P, Chirravuri VR, Sengupta K,Golakoti T. Safety and toxicological evaluation of a novel anti-obesityformulation LI85008F in animals. Toxicol Mech Methods. 2010;20:59-68.

9. Schulz KF, Altman DG, Moher D, CONSORT Group. CONSORT 2010statement: updated guidelines for reporting parallel group randomizedtrials. J Clin Epidemiol. 2010;63:834-840.

10. Rioa-Hoyo A, Gutiérrez-Salmeán G. New dietary supplements for obe-sity: what we currently know. Curr Obes Rep. 2016;5:262-270.

11. Douketis JD, Macie C, Thabane L, Williamson DF. Systematic reviewof long-term weight loss studies in obese adults: clinical significanceand applicability to clinical practice. Int J Obes (Lond). 2005;29:1153-1167.

12. Ferrannini E, Sironi AM, Iozzo P, Gastaldelli A. Intra-abdominal adipos-ity, abdominal obesity, and cardiometabolic risk. Eur Heart J Suppl.2008;10:B4-B10.

13. Alberti KG, Zimmet P, Shaw J. The metabolic syndrome–a new world-wide definition. Lancet. 2005;366:1059-1062.

14. Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolicsyndrome: a joint interim statement of the international diabetes fed-eration task force on epidemiology and prevention; National Heart,

Lung, and Blood Institute; American Heart Association; world heartfederation; international atherosclerosis society; and InternationalAssociation for the Study of obesity. Circulation. 2009;120:1640-1645.

15. Kawada T. Body mass index is a good predictor of hypertension andhyperlipidemia in a rural Japanese population. Int J Obes Relat MetabDisord. 2002;26:725-729.

16. Fischer S, Schatz U, Julius U. Practical recommendations for the man-agement of hyperlipidemia. Atheroscler Suppl. 2015;18:194-198.

17. World Health Organization. Waist Circumference and Waist–Hip Ratio:Report of a WHO Expert Consultation, Geneva, 8–11 December, 2008.Geneva: World Health Organization; 2011. http://www.who.int/nutrition/publications/obesity/WHO_report_waistcircumference_and_waisthip_ratio/en/. Accessed October 24, 2017.

18. Lombard MJ, Steyn NP, Charlton KE, Senekal M. Application andinterpretation of multiple statistical tests to evaluate validity of dietaryintake assessment methods. Nutrition J. 2015;14:40.

How to cite this article: Dixit K, Kamath DV, Alluri KV,

Davis BA. Efficacy of a novel herbal formulation for weight

loss demonstrated in a 16-week randomized, double-blind,

placebo-controlled clinical trial with healthy overweight adults.

Diabetes Obes Metab. 2018;1–9. https://doi.org/10.1111/

dom.13443

DIXIT ET AL. 9

http://www.who.int/nutrition/publications/obesity/WHO_report_waistcircumference_and_waisthip_ratio/en/



https://doi.org/10.1111/dom.13443

https://doi.org/10.1111/dom.13443