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What is better to use in health and longevity supplements: whole plant derived compounds or isolated bioactive molecules?

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RG
Ruby Grewal Dec 08, 2020
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There are a number of natural compounds that are beneficial in treating various diseases and may be used to slow down aging including ginsenoside from ginseng, fisetin a flavonoid from strawberries, 6-gingerol from ginger, sulforaphane from cruciferous vegetables, and curcumin from turmeric (reviewed here). Many longevity studies have examined the effects of isolated bioactive molecules on life spans and health, but there are also some studies showing that in some cases, the whole plant compound may be more beneficial to health. This raises the question under what circumstances is it better to use whole plant derived compounds instead of isolated bioactive molecules to increase longevity and in treating age-related disease?

Turmeric is a spice that is the powdered form of the Curcuma longa plant root. It has anti-inflammatory and antioxidant properties, and has been used in Ayurvedic medicine in India to treat digestive issues, arthritis, and cardiovascular disorders. Turmeric contains many plant compounds including three curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin), volatile oils (natlantone, tumerone and zingiberone), and other proteins and sugars. Recent research has shown that turmeric can relieve symptoms of osteoarthritis through reduction of inflammation markers, reduce the risk of heart disease by reducing LDL cholesterol and triglycerides levels, improve blood sugar metabolism thereby reducing diabetes symptoms, and help in the treatment of colorectal cancer and Parkinson’s disease.

Curcumin is the primary active compound in turmeric. Studies have shown that it reduces symptoms of age-related diseases such as rheumatoid arthritis, pancreatic cancer, and colorectal cancer. Studies have also shown that curcumin could be more effective as an anti-inflammatory than ibuprofen and aspirin.

In comparing turmeric and curcumin, it has been shown that, in vitro, turmeric was better at suppressing the growth of tumor cells than curcumin alone. A study recently isolated a novel compound (β-sesquiphellandrene) from turmeric that has anti-cancer properties.
In contrast, a study found that curcumin was better at minimizing diabetes markers than turmeric. In addition, an animal study found that rats who received turmeric extracts enriched with curcuminoids had preserved bone mass, while rats given turmeric with a lower amount of added curcuminoids showed no effect. One of the drawbacks of curcumin is its low bioavailability. Research has shown that the bioavailability of curcumin could be enhanced by adding non-curcuminoid components of turmeric. Therefore, turmeric, and curcumin within turmeric, may have better bioavailability than curcumin alone.

These studies show that there are a number of considerations to take into account when designing experiments to examine the effects of natural substances on longevity and age-related disease. Reducing complex compounds to single bioactive molecules may be effective in some disease states but not others. What other examples are there of natural substances that may have more benefit as a whole plant compound as compared to isolated bioactive molecules?

[1]He Y, Yue Y, Zheng X, Zhang K, Chen S, Du Z. Curcumin, inflammation, and chronic diseases: how are they linked?. Molecules. 2015;20(5):9183-9213. Published 2015 May 20. doi:10.3390/molecules20059183

[2]Akuri MC, Barbalho SM, Val RM, Guiguer EL. Reflections about Osteoarthritis and Curcuma longa. Pharmacogn Rev. 2017;11(21):8-12. doi:10.4103/phrev.phrev_54_16

[3]Qin S, Huang L, Gong J, et al. Efficacy and safety of turmeric and curcumin in lowering blood lipid levels in patients with cardiovascular risk factors: a meta-analysis of randomized controlled trials. Nutr J. 2017;16(1):68. Published 2017 Oct 11. doi:10.1186/s12937-017-0293-y

[4]Maithili Karpaga Selvi N, Sridhar MG, Swaminathan RP, Sripradha R. Efficacy of Turmeric as Adjuvant Therapy in Type 2 Diabetic Patients. Indian J Clin Biochem. 2015;30(2):180-186. doi:10.1007/s12291-014-0436-2

[5]Sharma RA, McLelland HR, Hill KA, Ireson CR, Euden SA, Manson MM, Pirmohamed M, Marnett LJ, Gescher AJ, Steward WP. Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Clin Cancer Res. 2001 Jul;7(7):1894-900. PMID: 11448902.

[6]Ma XW, Guo RY. Dose-dependent effect of Curcuma longa for the treatment of Parkinson's disease. Exp Ther Med. 2017;13(5):1799-1805. doi:10.3892/etm.2017.4225

[7]Daily JW, Yang M, Park S. Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Med Food. 2016;19(8):717-729. PMID: 27533649. PMCID: PMC5003001. doi:10.1089/jmf.2016.3705

[8]Dhillon N, Aggarwal BB, Newman RA, Wolff RA, Kunnumakkara AB, Abbruzzese JL, Ng CS, Badmaev V, Kurzrock R. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res. 2008 Jul 15;14(14):4491-9. PMID: 18628464. doi:10.1158/1078-0432.CCR-08-0024.

[9]Carroll RE, Benya RV, Turgeon DK, et al. Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia [published correction appears in Cancer Prev Res (Phila). 2012 Dec;5(12):1407. Dosage error in article text]. Cancer Prev Res (Phila). 2011;4(3):354-364. PMID: 21372035. PMCID: PMC4136551. doi:10.1158/1940-6207.CAPR-10-0098.

[10]Takada Y, Bhardwaj A, Potdar P, Aggarwal BB. Nonsteroidal anti-inflammatory agents differ in their ability to suppress NF-kappaB activation, inhibition of expression of cyclooxygenase-2 and cyclin D1, and abrogation of tumor cell proliferation. Oncogene. 2004 Dec 9;23(57):9247-58. doi: 10.1038/sj.onc.1208169. PMID: 15489888.

[11]Kim JH, Gupta SC, Park B, Yadav VR, Aggarwal BB. Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis. Mol Nutr Food Res. 2012;56(3):454-465. doi:10.1002/mnfr.201100270

[12]Tyagi AK, Prasad S, Yuan W, Li S, Aggarwal BB. Identification of a novel compound (β-sesquiphellandrene) from turmeric (Curcuma longa) with anticancer potential: comparison with curcumin. Invest New Drugs. 2015 Dec;33(6):1175-86. doi: 10.1007/s10637-015-0296-5. Epub 2015 Nov 2. PMID: 26521943.

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[14]Wright LE, Frye JB, Timmermann BN, Funk JL. Protection of trabecular bone in ovariectomized rats by turmeric (Curcuma longa L.) is dependent on extract composition. J Agric Food Chem. 2010;58(17):9498-9504. doi:10.1021/jf101873f

[15]Antony B, Merina B, Iyer VS, Judy N, Lennertz K, Joyal S. A Pilot Cross-Over Study to Evaluate Human Oral Bioavailability of BCM-95CG (Biocurcumax), A Novel Bioenhanced Preparation of Curcumin. Indian J Pharm Sci. 2008 Jul-Aug;70(4):445-9. doi: 10.4103/0250-474X.44591. PMID: 20046768; PMCID: PMC2792534.

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Creative contributions

Whole plant foods and prebiotics: what we ought not to miss

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Subash Chapagain
Subash Chapagain Dec 08, 2020
We all are pretty much familiar with probiotics, but there is a whole another class of compounds and molecules known as prebiotics, which are the part of the undigested food ingredients that nevertheless have a strong influence on gut health. When we are vying to find the best candidate supplements for longevity, maybe we should not bypass this class of compounds, not sure without close scrutiny.
In 1995 Gibson and Roberfroid postulated prebiotics as “a non-digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, and thus improves host health ” which has been updated in 2008 as “a selectively fermented ingredient that results in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health” .

If there are any compounds that we need to consume not because we digest them but because we don’t, they are prebiotic. Not actively metabolising these classes of molecules and allowing them in the body not for food but for the data, these molecules rather play the role of some kind of messengers that help stimulate the growth of different microbes that are good for us. In fact, it is exactly like that! These compounds work as a trick to keep our gut healthy. However, to be prebiotic, any compound must pass these few criteria:

- should be resistant to acidic pH of the stomach and not ‘hydrolyzed’ by mammalian enzymes and also not absorbed in the gastrointestinal tract
- it should be ‘fermentable’ by the intestinal microbiota
- it should show selective stimulation of intestinal bacteria to improve the host’s health

The most known prebiotics are Fructo-oligosaccharides (FOS) and galactooligosaccharides (GOS), and trans-galacto-oligosaccharides (TOS). They are long-chain molecules that upon fermentation by the microbiota produce short chain fatty acids (SCFAs) including lactic acid, butyric acid and propionic acid. They can have a number of effects on the body: propionate influences T helper 2 cells in airways, as well as macrophages and bone marrow dendritic cell ; SCFAs reduce the colon’s pH Peptidoglycan is another prebiotic with different stimulative effects against pathogenic microbes. Also, SCFAs can diffuse to the blood circulation via enterocytes, and hence influence not just the GI tract but distant organs as well .

There are a lot of foods that we can get prebiotics from. Plants like dandelion green, dahila tuber, garlic, gourd-type vegetables, mushrooms and barley are all deemed to be rich in prebiotics. Plant foods like legumes that contain dietary fibre can also have prebiotic potential. Chickpea kernel fibre is reported to stimulate colon bifidobacterium growth . A palm indigenous to South-East Asia contains 60% resistant starch. Called sago starch, it has the ability to increase Lactobacillus and Bifidobacterium spp populations

These are just some examples. FOS can be found in more than 36,000 plants , and if we could properly determine the role of these prebiotic compounds and the average requirement, it would enable us to design food supplements that can work in conjunction with probiotics.



[1]Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr. 1995 Jun;125(6):1401-12. doi: 10.1093/jn/125.6.1401. PMID: 778289

[2]Gibson G.R., Scott K.P., Rastall R.A., Tuohy K.M., Hotchkiss A., Dubert-Ferrandon A., Gareau M., Murphy E.F., Saulnier D., Loh G., et al. Dietary prebiotics: Current status and new definition. Food Sci. Technol. Bull. Funct. Foods. 2010;7:1–19. doi: 10.1616/1476-2137.

[3]Stinson LF, Payne MS, Keelan JA. Planting the seed: Origins, composition, and postnatal health significance of the fetal gastrointestinal microbiota. Crit Rev Microbiol. 2017 May;43(3):352-369. doi: 10.1080/1040841X.2016.1211088. Epub 2016 Dec 8. PMID: 27931152

[4]Zhou Z, Zhang Y, Zheng P, Chen X, Yang Y. Starch structure modulates metabolic activity and gut microbiota profile. Anaerobe. 2013 Dec;24:71-8. doi: 10.1016/j.anaerobe.2013.09.012. Epub 2013 Oct 7. PMID: 24113693.

[5]den Besten G., van Eunen K., Groen A.K., Venema K., Reijngoud D.-J., Bakker B.M. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J. Lipid Res. 2013;54:2325–2340. doi: 10.1194/jlr.R036012

[6] Smith, S.C., Choy, R., Johnson, S.K., Hall, R.S., Wildeboer‐Veloo, A.C.M. and Welling, G.W. (2006) Lupin kernel fiber consumption modifies faecal microbiota in healthy men as determined by rRNA gene fluorescent in situ hybridization. Eur J Nutr 45, 335–341.

[7]Arshad, N.S., Zaman, S.A., Rawi, M.H. and Sarbini, S.R. (2018) Resistant starch evaluation and in vitro fermentation of lemantak (native sago starch), for prebiotic assessment. Int Food Res J 25, 951–957.

[8] Havenaar R., Bonnin-Marol S., Van Dokkum W., Petitet S., Schaafsma G. Inulin: Fermentation and microbial ecology in the intestinal tract. Food Rev. Int. 1999;15:109–120. doi: 10.1080/87559129909541179.

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RG
Ruby Grewal10 months ago
Prebiotics and probiotics are another great example. While it is important to understand the effect of each individual product or molecule on human health, if we are talking about getting a supplement approved that has significant benefit for human longevity, it will most likely require a combinatorial approach.
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