1. Jungwei Fan Yves Lussier The University of Arizona
Word-of-Mouth Innovation:
Hypothesis generation for supplement repurposing based on consumer reviews
Session #S106
Jungwei Fan
Yves Lussier
The University of Arizona

2. Disclosure
The authors and their spouses/partners have no relevant relationships with commercial interests to disclose.
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3. Motivation Economy in discovering new use of existing substances
Consumer reviews are massive but overlooked in repurposing
Systematic mining methods to facilitate:
Identifying repurposable candidates
Generating biological hypotheses
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4. Why dietary supplements?
68% of Americans use dietary supplements
66% of those users between age plan to use more
Diversely affecting health: minerals, vitamins, amino acids, enzymes, herbals and botanicals
Popular source for searching “analogues” of already repositioned chemicals (e.g., sildenafil)
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5. Why consumer reviews? Huge consumer base
e.g., Amazon.com has >300 million users and $136 billion net sales
Wide coverage of health products
19,619 Multi & prenatal vitamins
42,519 Herbal supplements
12,370 Weight loss products
Currency of the data
Constantly growing
Reflecting what people use
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6. Methods
Regex-screened 2,982,326 Amazon reviews on health and personal care products
\\b((unexpected|unintended|unanticipated|surprising)\\s+
(effects?|benefits?))\\b
Manually analyzed the TPs and FPs
Biological hypothesis generation by looking up databases:
Diseases – GWAS Catalog
Supplements – Comparative Toxicogenomics Database (CTD)
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7. Analysis of the matched
Category
Count (%)
Example TP
77 (45.6%)
Arginine helped quit smoke by putting off desire for cigarettes
Non-dietary
76 (45.0%)
Heart rate monitor, electric toothbrush, etc.
Neutral (or debatable) effect
10 (6.0%)
Enhanced flavor, lost appetite…
Unspecified effect
6 (3.4%)
“If you do a little research you may find some surprising benefits to xylitol”
Among the true positives, there were five substance-effect associations supported by more than one review.
For example, unexpected weight loss from using products of vitamin B2.
Although infrequent, those irrelevant cases indicate the regex-based approach may still pick up some noise.
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8. TP examples Product Unexpected effect Hair regrowth tablets
Everyone around me was being bit (by mosquitos) and I wasn't bit once
Ashwagandha extract capsule
Took away the negative symptoms of IBS (with constipation) of which I have suffered for 33 years
Inositol powder
A significant reduction in the number of heart palpitations I have
Resveratrol capsule
A rather stubborn bout of eczema on my feet cleared up after being there for two years
By inspecting the true positive reviews and product information, we found that about a half of the consumer-claimed “unexpected” benefits might actually be expected.
Given the subjective nature, it is not uncommon that the reviewers were surprised due to lack of domain knowledge or just did not pay attention to the product labels.
Ashwagandha extract capsules (marketed as a general healthy herb supplement)
Inositol powder (marketed for liver function support)
Resveratrol (marketed as general healthy juice capsule)
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9. Biological underpinning?
Ashwagandha
IBS
Gene ID: Symbol: CAT
Gene ID: Symbol: SPATA5
Gene ID: Symbol: GFAP
Gene ID: Symbol: HES6
Gene ID: Symbol: HSPA2
Gene ID: Symbol: PER2
Gene ID: Symbol: HSPA9
Gene ID: Symbol: PCDH15
Gene ID: Symbol: NCAM1
Gene ID: Symbol: KDELR2
Gene ID: Symbol: SOD1
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10. Biological underpinning?
Figure 1 illustrates a couple of the GO Biological Process terms between SOD1 (ashwagandha) and PER2 (IBS), with information-theoretic similarity scores computed using our previously published method.
For GO Molecular Function terms, we also observed overlaps such as protein binding (GO: ) shared between PER2 (IBS) and HSPA9 (ashwagandha).
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11. Consumer reviews as innovation driver
Systematic integration of consumer experience with scientific knowledge bases to inspire pharmacogenomics
Useful signals existed in consumer reviews way before formal studies/publications
Probiotics and sleep improvement (2013  2016)
Recombinant hGH and cognitive enhancement (2006  2013)
Patentable ideas may exist in consumer reviews and not reported by research literature
Resveratrol for treating eczema
In 2013, a consumer reported eczema was resolved by dietary resveratrol, which does not seem to have been reported in literature.
Interestingly, a US patent was filed in 2001 for external use of resveratrol for treating exfoliative eczema, acne, and psoriasis.
Due to less stringent regulation, this example suggests that supplement-based intellectual property could be nimbly registered as soon as a promising effect is found.
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12. Potential model of citizen science
Encourage lay people to help research studies
Diverse products, many consumers, and constant monitoring
 Supplement repurposing as “crowd-sourced observational trial”
Informatics to help !!
Data integration
Semantic harmonization
Workflow automation
Consumer engagement/training
An interesting observation was how some consumers described in reviews that they tested the effect via self-controlled experiment, i.e., verifying the effect by stopping use and resuming again. This suggests that, with moderate scientific training, we could further improve the quality of data collected from general consumers.
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13. Limitations The review curation was done by only one annotator
Did not perform formal evaluation with a reference standard
Some reviews were anecdotal by nature and of varying quality dependent on the consumer’s background
Multi-ingredient supplements posed challenges in pinpointing the exact active element that caused the effect
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14. Conclusion
Proof-of-concept study exercised a workflow of mining unexpected benefits from massive consumer reviews
45.6% of the 169 mined reviews contained user-claimed unexpected benefits from dietary supplements
Some of the cases demonstrated potential value for driving repurposing innovation
The hypothesis enrichment derived informative (possible) functional association between a supplement and a disease
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15. AMIA is the professional home for more than 5,400 informatics professionals, representing frontline clinicians, researchers, public health experts and educators who bring meaning to data, manage information and generate new knowledge across the research and healthcare enterprise.
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16. Email me at: fanj@email.arizona.edu
Thank you!
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