The Metabolism of Plant Lignans via Human Intestinal Microbiota

Thinkingbact1 GutBacteriaFactory1


Hey kiddos! I’m working on a series of posts on gut bacteria and I thought I’d start off with a post about the gut bacterial metabolism of plant lignans and its role in health and disease, primarily because it is something I know a great deal about. Or should I say “it is something about which I know a great deal”? Probably the latter. Proper use of prepositional phrases confounds me sometimes. Wait, this isn’t a blog about grammar; it’s about nutrition! Moving on…

What are lignans?

Lignans are polyphenolic compounds found in many plants that play a role in plant defense. It’s really quite extraordinary what lignans do for the plant. They have quite an array of defensive properties, protecting the plant from harmful pests and pathogens.1 For example, lignans have been shown to have insecticidal properties comparable to that of pyrethrins.2 If you have ever used that to kill aphids in your home garden then you know how powerful that is. They also have other properties that protect plants such as antifungal properties and somewhat paradoxically antimicrobial properties.3,4 I say “paradoxically” because I am about to discuss the fact that some species of bacteria that can live in the gut go nuts for these lignans.

Lignans are not to be confused with their homophone lignins, which are kinda similar in that they are also found in plants and are chemically related. However, lignins are much larger polymers that intercalate with cellulose and hemicellulose within the cell wall to provide structure and support. Interestingly though, since there are lignan structures within the larger lignin molecule, gut bacteria are able to metabolize lignins to some degree and “release” lignans for further metabolism.5,6



What Foods are Lignans Found In?

Or maybe I should say “In What Foods are Lignans Found?” Damn those prepositional phrases! So they are found in a variety of foods. You can find a fair amount in cereal grains (corn, oats, wheat, rye), cruciferous vegetables, fruits (like apricots, oranges, kiwi, strawberries), and you can even find small amounts in beverages like coffee, tea, beer, and wine.7–31 But by far the largest concentration of lignans can be found in seeds, particularly flaxseeds. Seriously. A handful of flaxseeds contain about ten thousand times more lignans than an equivalent amount of broccoli, and about a hundred thousand times the lignans of, say, an orange.


So Where do Gut Bacteria Come In?

Or should I say “In Where do Gut –“ ah, forget it. So it turns out that plant lignans can be converted to what are sometimes called mammalian lignans or enterolignans by bacteria found in the gut.8,32–68 There are several steps involved when converting a plant lignan to an enterolignan, however, and as far as we know there is not one bacterium that can catalyze all the reactions. Rather, a consortium of bacteria is needed to complete the conversion to the enterolignans enterodiol and/or enterolactone. These more physiologically active enterolignans then get absorbed via colonic epithelial cells.69

But the thing is that not everyone possesses the bacterial community necessary to complete this transformation. According to research by Possemiers and others maybe about 2/3rds of the population has the appropriate species in their gut to convert lignans to enterodiol and far fewer are able to convert lignans to enterolactone.70

Metabolism of isoflavones, lignans and prenylflavonoids by intestinal bacteria producer phenotyping and relation with intestinal community.


diagram w bacteria

Here’s a little diagram I made of common food lignans and the bacteria that convert them. Or at least some of them.

I made a diagram of sesaminol if you’d like to see that, too.

Why Should I Care About Lignans Anyway?

There is quite a bit of evidence that lignans have a variety of beneficial health effects.71–90 Let’s look at all these bennies in slightly more detail.

In Vitro Evidence

  • Lignans inhibit the proliferation of cancer cells.91–107
  • Lignans suppress the flu virus.108
  • Lignans have antimicrobial activity.109
  • Provide therapeutic effects to cardiovascular tissue by promoting vasorelaxation and reducing fibrosis, inflammation, apoptosis, and oxidative stress.110,111
  • Have neuroprotective effects.112,113
  • General antioxidant and anti-inflammatory effects.114
  • Prevents angiogenesis.115

Evidence from Animal Studies

  • A topical cream made with flax lignans aid in wound healing by their antioxidant activity and stimulating collagen synthesis.116
  • Reduced breast tumors.117–121
  • Protects bone tissue.122
  • Can reduce pain and inflammation.123
  • Improves vascular biomarkers.124–126
  • Reduces radiation damage.127
  • Reduced colon cancer biomarkers.128
  • Reduced biomarkers of liver cancer.129

Human Studies

Epidemiological Evidence

  • Lignan intake is negatively associated with esophageal cancer.130
  • Enterolignans are associated with a reduced risk of type 2 diabetes.131
  • Enterolactone levels are negatively associated with asthma.132
  • Lignan intake is negatively associated with bladder cancer, especially urothelial cell carcinoma.133
  • Reduced risk of breast cancer.117,134–144
  • Associated with reduced risk of colon cancer.140,145–148
  • Associated with a decreased risk of prostate cancer.140,148–150
  • Lignans are associated with a reduction in cardiovascular disease risk factors.151–153
  • Inversely associated with obesity and overweight.154

Clinical Trials

  • Flaxseed intake improves lipid profiles and reduces CVD risk factors.155–157
  • Might reduce breast tumor growth.117,158
  • Small reductions in prostate cancer biomarkers.159
  • Lignans attenuate blood glucose levels.160

Not-So-Good Outcomes

There is some evidence that lignans might not be so beneficial, particularly in men. This may be due to the fact that plant lignans and enterolignans are considered to be phytoestrogens with weak estrogenic and antiestrogenic properties.56,161–163

  • Associated with male infertility.164
  • Associated with an increase in prostate cancer.165,166


Despite the bit of evidence that dietary lignans may not be so good for men, I would say that the benefits outweigh the risks, especially if you are one of the lucky people to have the gut bacterial community that makes for efficient lignan conversion.


1            Pan J-Y, Chen S-L, Yang M-H, Wu J, Sinkkonen J, Zou K. An update on lignans: natural products and synthesis. Nat Prod Rep 2009; 26: 1251–92.

2            Harmatha J, Dinan L. Biological activities of lignans and stilbenoids associated with plant-insect chemical interactions. Phytochem Rev 2003; 2: 321–30.

3            Gang DR, Dinkova-Kostova AT, Davin LB, Lewis NG. Phylogenetic Links in Plant Defense Systems: Lignans, Isoflavonoids, and Their Reductases. In: Hedin PA, Hollingworth RM, Masler EP, Miyamoto J, eds. Phytochemicals for Pest Control. Washington, DC, American Chemical Society, 1997: 59–89.

4            Lewis NG, Kato MJ, Lopes N, Davin LB. Lignans: Diversity, Biosynthesis, and Function. In: Seidl PR, Gottlieb OR, Kaplan MAC, eds. Chemistry of the Amazon. Washington, DC, American Chemical Society, 1995: 135–67.

5            Niemi P, Aura A-M, Maukonen J, et al. Interactions of a Lignin-Rich Fraction from Brewer’s Spent Grain with Gut Microbiota In Vitro. J Agric Food Chem 2013. doi:10.1021/jf401738x.

6            Begum AN, Nicolle C, Mila I, et al. Dietary lignins are precursors of mammalian lignans in rats. J Nutr 2004; 134: 120–7.

7            Blitz CL, Murphy SP, Au DLM. Adding lignan values to a food composition database. J Food Compos Anal 2007; 20: 99–105.

8            Coulman KD, Liu Z, Hum WQ, Michaelides J, Thompson LU. Whole sesame seed is as rich a source of mammalian lignan precursors as whole flaxseed. Nutr Cancer 2005; 52: 156–65.

9            Hao M, Beta T. Qualitative and quantitative analysis of the major phenolic compounds as antioxidants in barley and flaxseed hulls using HPLC/MS/MS. J Sci Food Agric 2012; 92: 2062–8.

10         Horn-Ross PL, Barnes S, Lee M, et al. Assessing phytoestrogen exposure in epidemiologic studies: development of a database (United States). Cancer Causes Control 2000; 11: 289–98.

11         Huang M-H, Norris J, Han W, et al. Development of an updated phytoestrogen database for use with the SWAN food frequency questionnaire: intakes and food sources in a community-based, multiethnic cohort study. Nutr Cancer 2012; 64: 228–44.

12         Johnsson P, Kamal-Eldin A, Lundgren LN, Aman P. HPLC method for analysis of secoisolariciresinol diglucoside in flaxseeds. J Agric Food Chem 2000; 48: 5216–9.

13         Kraushofer T, Sontag G. Determination of some phenolic compounds in flax seed and nettle roots by HPLC with coulometric electrode array detection. Eur Food Res Technol 2002; 215: 529–33.

14         Mazur W. Phytoestrogen content in foods. Baillieres Clin Endocrinol Metab 1998; 12: 729–42.

15         Mazur W, Adlercreutz H. Naturally occurring oestrogens in food. Pure Appl Chem 1998; 70: 1759–76.

16         Mazur WM, Duke JA, Wähälä K, Rasku S, Adlercreutz H. Isoflavonoids and Lignans in Legumes: Nutritional and Health Aspects in Humans. J Nutr Biochem 1998; 9: 193–200.

17         Meagher LP, Beecher GR. Assessment of Data on the Lignan Content of Foods. J Food Compos Anal 2000; 13: 935–47.

18         Milder IEJ, Arts ICW, van de Putte B, Venema DP, Hollman PCH. Lignan contents of Dutch plant foods: a database including lariciresinol, pinoresinol, secoisolariciresinol and matairesinol. Br J Nutr 2005; 93: 393–402.

19         Owen RW, Mier W, Giacosa A, Hull WE, Spiegelhalder B, Bartsch H. Identification of lignans as major components in the phenolic fraction of olive oil. Clin Chem 2000; 46: 976–88.

20         Peñalvo JL, Haajanen KM, Botting N, Adlercreutz H. Quantification of lignans in food using isotope dilution gas chromatography/mass spectrometry. J Agric Food Chem 2005; 53: 9342–7.

21         Smeds AI, Eklund PC, Sjöholm RE, et al. Quantification of a broad spectrum of lignans in cereals, oilseeds, and nuts. J Agric Food Chem 2007; 55: 1337–46.

22         Smeds AI, Jauhiainen L, Tuomola E, Peltonen-Sainio P. Characterization of variation in the lignan content and composition of winter rye, spring wheat, and spring oat. J Agric Food Chem 2009; 57: 5837–42.

23         Kuhnle GGC, Dell’Aquila C, Aspinall SM, Runswick S a, Mulligan A a, Bingham S a. Phytoestrogen content of beverages, nuts, seeds, and oils. J Agric Food Chem 2008; 56: 7311–5.

24         Kuhnle GGC, Dell’aquila C, Aspinall SM, Runswick S a, Mulligan A a, Bingham S a. Phytoestrogen content of cereals and cereal-based foods consumed in the UK. Nutr Cancer 2009; 61: 302–9.

25         Mazur WM, Wähälä K, Rasku S, Salakka A, Hase T, Adlercreutz H. Lignan and isoflavonoid concentrations in tea and coffee. Br J Nutr 1998; 79: 37–45.

26         Peñalvo JL, Adlercreutz H, Uehara M, Ristimaki A, Watanabe S. Lignan content of selected foods from Japan. J Agric Food Chem 2008; 56: 401–9.

27         Smeds AI, Eklund PC, Willför SM. Content, composition, and stereochemical characterisation of lignans in berries and seeds. Food Chem 2012; 134: 1991–8.

28         Thompson LU, Boucher B a, Liu Z, Cotterchio M, Kreiger N. Phytoestrogen content of foods consumed in Canada, including isoflavones, lignans, and coumestan. Nutr Cancer 2006; 54: 184–201.

29         Valsta LM, Kilkkinen A, Mazur W, et al. Phyto-oestrogen database of foods and average intake in Finland. Br J Nutr 2003; 89 Suppl 1: S31–8.

30         Tetens I, Turrini A, Tapanainen H, et al. Dietary intake and main sources of plant lignans in five European countries. Food Nutr Res 2013; 57. doi:10.3402/fnr.v57i0.19805.

31         Meija L, Söderholm P, Samaletdin A, et al. Dietary intake and major sources of plant lignans in Latvian men and women. Int J Food Sci Nutr 2013; 64: 622–30.

32         Aura A-M, Karppinen S, Virtanen H, et al. Processing of rye bran influences both the fermentation of dietary fibre and the bioconversion of lignans by human faecal florain vitro. J Sci Food Agric 2005; 85: 2085–93.

33         Aura A-M, Myllymäki O, Bailey M, Penalvo JL, Adlercreutz H, Poutanen K. Interrelationships between carbohydrate type, phenolic acids and initial pH on in vitro conversion of enterolactone from rye lignans. In: Salovaara H, Gates F, Tenkanen M, eds. Dietary Fibre: Components and Functions. Wageningen, The Netherlands, Wageningen Academic Publishers, 2007: 235–45.

34         Aura A-M, Oikarinen S, Mutanen M, et al. Suitability of a batch in vitro fermentation model using human faecal microbiota for prediction of conversion of flaxseed lignans to enterolactone with reference to an in vivo rat model. Eur J Nutr 2006; 45: 45–51.

35         Bartkiene E, Juodeikiene G, Basinskiene L. In Vitro Fermentative Production of Plant Lignans from Cereal Products in Relationship with Constituents of Non-Starch Polysaccharides. Food Technol Biotechnol 2012; 50: 237–45.

36         Bartkiene E, Juodeikiene G, Basinskiene L, Liukkonen K-H, Adlercreutz H, Kluge H. Enterolignans enterolactone and enterodiol formation from their precursors by the action of intestinal microflora and their relationship with non-starch polysaccharides in various berries and vegetables. LWT–Food Sci Technol 2011; 44: 48–53.

37         Borriello SP, Setchell KD, Axelson M, Lawson AM. Production and metabolism of lignans by the human faecal flora. J Appl Bacteriol 1985; 58: 37–43.

38         Clavel T, Borrmann D, Braune A, Doré J, Blaut M. Occurrence and activity of human intestinal bacteria involved in the conversion of dietary lignans. Anaerobe 2006; 12: 140–7.

39         Clavel T, Lippman R, Gavini F, Doré J, Blaut M. Clostridium saccharogumia sp. nov. and Lactonifactor longoviformis gen. nov., sp. nov., two novel human faecal bacteria involved in the conversion of the dietary phytoestrogen secoisolariciresinol diglucoside. Syst Appl Microbiol 2007; 30: 16–26.

40         Clavel T, Henderson G, Engst W, Doré J, Blaut M. Phylogeny of human intestinal bacteria that activate the dietary lignan secoisolariciresinol diglucoside. FEMS Microbiol Ecol 2006; 55: 471–8.

41         Clavel T, Henderson G, Alpert C-A, et al. Intestinal bacterial communities that produce active estrogen-like compounds enterodiol and enterolactone in humans. Appl Env Microbiol 2005; 71: 6077–85.

42         Clavel T, Doré J, Blaut M. Bioavailability of lignans in human subjects. Nutr Res Rev 2006; 19: 187–96.

43         Heinonen S, Nurmi T, Liukkonen K, et al. In vitro metabolism of plant lignans: new precursors of mammalian lignans enterolactone and enterodiol. J Agric Food Chem 2001; 49: 3178–86.

44         Jan K-C, Hwang LS, Ho C-T. Biotransformation of sesaminol triglucoside to mammalian lignans by intestinal microbiota. J Agric Food Chem 2009; 57: 6101–6.

45         Jin J-S, Zhao Y-F, Nakamura N, et al. Enantioselective dehydroxylation of enterodiol and enterolactone precursors by human intestinal bacteria. Biol Pharm Bull 2007; 30: 2113–9.

46         Jin J-S, Kakiuchi N, Hattori M. Enantioselective oxidation of enterodiol to enterolactone by human intestinal bacteria. Biol Pharm Bull 2007; 30: 2204–6.

47         Jin J-S, Hattori M. Human intestinal bacterium, strain END-2 is responsible for demethylation as well as lactonization during plant lignan metabolism. Biol Pharm Bull 2010; 33: 1443–7.

48         Jin J-S, Hattori M. Further studies on a human intestinal bacterium Ruminococcus sp. END-1 for transformation of plant lignans to mammalian lignans. J Agric Food Chem 2009; 57: 7537–42.

49         Li M-X, Zhu H-Y, Yang D-H, et al. Production of secoisolariciresinol from defatted flaxseed by bacterial biotransformation. J Appl Microbiol 2012; 113: 1352–61.

50         Roncaglia L, Amaretti A, Raimondi S, Leonardi A, Rossi M. Role of bifidobacteria in the activation of the lignan secoisolariciresinol diglucoside. Appl Microbiol Biotechnol 2011; 92: 159–68.

51         Setchell KDR, Brown NM, Zimmer-Nechemias L, Wolfe B, Jha P, Heubi JE. Metabolism of secoisolariciresinol-diglycoside the dietary precursor to the intestinally derived lignan enterolactone in humans. Food Funct 2014; 5: 491–501.

52         Struijs K, Vincken J-P, Gruppen H. Bacterial conversion of secoisolariciresinol and anhydrosecoisolariciresinol. J Appl Microbiol 2009; 107: 308–17.

53         Eeckhaut E, Struijs K, Possemiers S, Vincken J-P, Keukeleire D De, Verstraete W. Metabolism of the lignan macromolecule into enterolignans in the gastrointestinal lumen as determined in the simulator of the human intestinal microbial ecosystem. J Agric Food Chem 2008; 56: 4806–12.

54         Wang C-Z, Ma X-Q, Yang D-H, et al. Production of enterodiol from defatted flaxseeds through biotransformation by human intestinal bacteria. BMC Microbiol 2010; 10: 115.

55         Wang LQ, Meselhy MR, Li Y, Qin GW, Hattori M. Human intestinal bacteria capable of transforming secoisolariciresinol diglucoside to mammalian lignans, enterodiol and enterolactone. Chem Pharm Bull 2000; 48: 1606–10.

56         Xie L-H, Ahn E-M, Akao T, Abdel-Hafez AA-M, Nakamura N, Hattori M. Transformation of arctiin to estrogenic and antiestrogenic substances by human intestinal bacteria. Chem Pharm Bull 2003; 51: 378–84.

57         Xie L-H, Akao T, Hamasaki K, Deyama T, Hattori M. Biotransformation of pinoresinol diglucoside to mammalian lignans by human intestinal microflora, and isolation of Enterococcus faecalis strain PDG-1 responsible for the transformation of (+)-pinoresinol to (+)-lariciresinol. Chem Pharm Bull 2003; 51: 508–15.

58         Horner NK, Kristal AR, Prunty J, Skor HE, Potter JD, Lampe JW. Dietary determinants of plasma enterolactone. Cancer Epidemiol Biomarkers Prev 2002; 11: 121–6.

59         Hutchins AM, Martini MC, Olson BA, Thomas W, Slavin JL. Flaxseed influences urinary lignan excretion in a dose-dependent manner in postmenopausal women. Cancer Epidemiol Biomarkers Prev 2000; 9: 1113–8.

60         Juntunen KS, Mazur WM, Liukkonen KH, et al. Consumption of wholemeal rye bread increases serum concentrations and urinary excretion of enterolactone compared with consumption of white wheat bread in healthy Finnish men and women. Br J Nutr 2000; 84: 839–46.

61         Kilkkinen A, Stumpf K, Pietinen P, Valsta LM, Tapanainen H, Adlercreutz H. Determinants of serum enterolactone concentration. Am J Clin Nutr 2001; 73: 1094–100.

62         Kilkkinen A, Valsta LM, Virtamo J, Stumpf K, Adlercreutz H, Pietinen P. Intake of lignans is associated with serum enterolactone concentration in Finnish men and women. J Nutr 2003; 133: 1830–3.

63         Kilkkinen A, Pietinen P, Klaukka T, Virtamo J, Korhonen P, Adlercreutz H. Use of oral antimicrobials decreases serum enterolactone concentration. Am J Epidemiol 2002; 155: 472–7.

64         Knust U, Spiegelhalder B, Strowitzki T, Owen RW. Contribution of linseed intake to urine and serum enterolignan levels in German females: a randomised controlled intervention trial. Food Chem Toxicol 2006; 44: 1057–64.

65         Kurzer MS, Lampe JW, Martini MC, Adlercreutz H. Fecal lignan and isoflavonoid excretion in premenopausal women consuming flaxseed powder. Cancer Epidemiol Biomarkers Prev 1995; 4: 353–8.

66         Lampe JW, Martini MC, Kurzer MS, Adlercreutz H, Slavin JL. Urinary lignan and isoflavonoid excretion in premenopausal women consuming flaxseed powder. Am J Clin Nutr 1994; 60: 122–8.

67         Nesbitt PD, Lam Y, Thompson LU. Human metabolism of mammalian lignan precursors in raw and processed flaxseed. Am J Clin Nutr 1999; 69: 549–55.

68         Peñalvo JL, Heinonen S-M, Aura A-M, Adlercreutz H. Dietary sesamin is converted to enterolactone in humans. J Nutr 2005; 135: 1056–62.

69         Jansen GHE, Arts ICW, Nielen MWF, Müller M, Hollman PCH, Keijer J. Uptake and metabolism of enterolactone and enterodiol by human colon epithelial cells. Arch Biochem Biophys 2005; 435: 74–82.

70         Possemiers S, Bolca S, Eeckhaut E, Depypere H, Verstraete W. Metabolism of isoflavones, lignans and prenylflavonoids by intestinal bacteria: producer phenotyping and relation with intestinal community. FEMS Microbiol Ecol 2007; 61: 372–83.

71         Wang L. Mammalian phytoestrogens: enterodiol and enterolactone. J Chromatogr, B Anal Technol Biomed Life Sci 2002; 777: 289–309.

72         Westcott ND, Muir AD. Flax seed lignan in disease prevention and health promotion. Phytochem Rev 2003; 2: 401–17.

73         Touré A, Xueming X. Flaxseed Lignans: Source, Biosynthesis, Metabolism, Antioxidant Activity, Bio-Active Components, and Health Benefits. Compr Rev Food Sci Food Saf 2010; 9: 261–9.

74         Thompson LU. Experimental studies on lignans and cancer. Baillieres Clin Endocrinol Metab 1998; 12: 691–705.

75         Tham DM, Gardner CD, Haskell WL. Potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological, and mechanistic evidence. J Clin Endocrinol Metab 1998; 83: 2223–35.

76         Peterson J, Dwyer J, Adlercreutz H, Scalbert A, Jacques P, McCullough ML. Dietary lignans: physiology and potential for cardiovascular disease risk reduction. Nutr Rev 2010; 68: 571–603.

77         Landete JM. Plant and mammalian lignans: A review of source, intake, metabolism, intestinal bacteria and health. Food Res Int 2012; 46: 410–24.

78         Kurzer MS, Xu X. Dietary phytoestrogens. Annu Rev Nutr 1997; 17: 353–81.

79         Dar AA, Arumugam N. Lignans of sesame: purification methods, biological activities and biosynthesis–a review. Bioorg Chem 2013; 50: 1–10.

80         Adolphe JL, Whiting SJ, Juurlink BHJ, Thorpe LU, Alcorn J. Health effects with consumption of the flax lignan secoisolariciresinol diglucoside. Br J Nutr 2010; 103: 929–38.

81         Adlercreutz H. Phyto-oestrogens and cancer. Lancet Oncol 2002; 3: 364–73.

82         Adlercreutz H. Lignans and human health. Crit Rev Clin Lab Sci 2007; 44: 483–525.

83         Adlercreutz H, Heinonen S-M, Penalvo-Garcia J. Phytoestrogens, cancer and coronary heart disease. BioFactors 2004; 22: 229–36.

84         Sok D-E, Cui HS, Kim MR. Isolation and bioactivities of furfuran type lignan compounds from edible plants. Recent Pat Food, Nutr Agric 2009; 1: 87–95.

85         Sainvitu P, Nott K, Richard G, et al. Structure , properties and obtention routes of flaxseed lignan secoisolariciresinol : a review. Biotechnol, Agron, Soc Env 2012; 16: 115–24.

86         Bolca S, Van de Wiele T, Possemiers S. Gut metabotypes govern health effects of dietary polyphenols. Curr Opin Biotechnol 2013; 24: 220–5.

87         Adlercreutz H, Mazur W, Bartels P, et al. Phytoestrogens and prostate disease. J Nutr 2000; 130: 658S – 9S.

88         Cardoso Carraro JC, Dantas MI de S, Espeschit ACR, Martino HSD, Ribeiro SMR. Flaxseed and Human Health: Reviewing Benefits and Adverse Effects. Food Rev Int 2012; 28: 203–30.

89         Adlercreutz H. Phytoestrogens: epidemiology and a possible role in cancer protection. Env Heal Perspect 1995; 103 Suppl: 103–12.

90         Bedell S, Nachtigall M, Naftolin F. The pros and cons of plant estrogens for menopause. J Steroid Biochem Mol Biol 2014; 139: 225–36.

91         Jafari S, Saeidnia S, Abdollahi M. Role of Natural Phenolic Compounds in Cancer Chemoprevention via Regulation of the Cell Cycle. Curr Pharm Biotechnol 2014; 15: 409–21.

92         Casarin E, Dall’Acqua S, Smejkal K, Slapetová T, Innocenti G, Carrara M. Molecular mechanisms of antiproliferative effects induced by Schisandra-derived dibenzocyclooctadiene lignans (+)-deoxyschisandrin and (-)-gomisin N in human tumour cell lines. Fitoterapia 2014; 98: 241–7.

93         Kong X, Ma M, Zhang Y, et al. Differentiation therapy: sesamin as an effective agent in targeting cancer stem-like side population cells of human gallbladder carcinoma. BMC Complement Altern Med 2014; 14: 254.

94         Kim KH, Woo KW, Moon E, et al. Identification of antitumor lignans from the seeds of morning glory (Pharbitis nil). J Agric Food Chem 2014; 62: 7746–52.

95         Kong P, Zhang L, Guo Y, Lu Y, Lin D. Phillyrin, a natural lignan, attenuates tumor necrosis factor α-mediated insulin resistance and lipolytic acceleration in 3T3-L1 adipocytes. Planta Med 2014; 80: 880–6.

96         Kang K, Nho CW, Kim ND, et al. Daurinol, a catalytic inhibitor of topoisomerase IIα, suppresses SNU-840 ovarian cancer cell proliferation through cell cycle arrest in S phase. Int J Oncol 2014; 45: 558–66.

97         Shimizu S, Fujii G, Takahashi M, et al. Sesamol suppresses cyclooxygenase-2 transcriptional activity in colon cancer cells and modifies intestinal polyp development in Apc (Min/+) mice. J Clin Biochem Nutr 2014; 54: 95–101.

98         Luo J, Hu Y, Kong W, Yang M. Evaluation and structure-activity relationship analysis of a new series of arylnaphthalene lignans as potential anti-tumor agents. PLoS One 2014; 9: e93516.

99         Saeed M, Khalid H, Sugimoto Y, Efferth T. The lignan, (-)-sesamin reveals cytotoxicity toward cancer cells: pharmacogenomic determination of genes associated with sensitivity or resistance. Phytomedicine 2014; 21: 689–96.

100      Qu H, Madl RL, Takemoto DJ, Baybutt RC, Wang W. Lignans are involved in the antitumor activity of wheat bran in colon cancer SW480 cells. J Nutr 2005; 135: 598–602.

101      Saggar JK, Chen J, Corey P, Thompson LU. The effect of secoisolariciresinol diglucoside and flaxseed oil, alone and in combination, on MCF-7 tumor growth and signaling pathways. Nutr Cancer 2010; 62: 533–42.

102      Wada-Hiraike O, Warner M, Gustafsson J. New developments in oestrogen signalling in colonic epithelium. Biochem Soc Trans 2006; 34: 1114–6.

103      Ford JD, Huang KS, Wang HB, Davin LB, Lewis NG. Biosynthetic pathway to the cancer chemopreventive secoisolariciresinol diglucoside-hydroxymethyl glutaryl ester-linked lignan oligomers in flax (Linum usitatissimum) seed. J Nat Prod 2001; 64: 1388–97.

104      Bailly F, Toillon R-A, Tomavo O, Jouy N, Hondermarck H, Cotelle P. Antiproliferative and apoptotic effects of the oxidative dimerization product of methyl caffeate on human breast cancer cells. Bioorg Med Chem Lett 2013; 23: 574–8.

105      Mali A V, Wagh U V, Hegde M V, Chandorkar SS, Surve S V, Patole M V. In vitro anti-metastatic activity of enterolactone, a mammalian lignan derived from flax lignan, and down-regulation of matrix metalloproteinases in MCF-7 and MDA MB 231 cell lines. Indian J Cancer 2012; 49: 181–7.

106      Macdonald RS, Wagner K. Influence of Dietary Phytochemicals and Microbiota on Colon Cancer Risk. J Agric Food Chem 2012. doi:10.1021/jf204230r.

107      McCann MJ, Rowland IR, Roy NC. Anti-proliferative effects of physiological concentrations of enterolactone in models of prostate tumourigenesis. Mol Nutr Food Res 2013; 57: 212–24.

108      Parhira S, Yang Z-F, Zhu G-Y, et al. In vitro anti-influenza virus activities of a new lignan glycoside from the latex of Calotropis gigantea. PLoS One 2014; 9: e104544.

109      Zuk M, Dorotkiewicz-Jach A, Drulis-Kawa Z, Arendt M, Kulma A, Szopa J. Bactericidal activities of GM flax seedcake extract on pathogenic bacteria clinical strains. BMC Biotechnol 2014; 14: 70.

110      Chun JN, Cho M, So I, Jeon J-H. The protective effects of Schisandra chinensis fruit extract and its lignans against cardiovascular disease: a review of the molecular mechanisms. Fitoterapia 2014; 97: 224–33.

111      Lee W, Ku S-K, Kim JA, Lee T, Bae J-S. Inhibitory effects of epi-sesamin on HMGB1-induced vascular barrier disruptive responses in vitro and in vivo. Toxicol Appl Pharmacol 2013; 267: 201–8.

112      Yu H-Y, Chen Z-Y, Sun B, et al. Lignans from the fruit of Schisandra glaucescens with antioxidant and neuroprotective properties. J Nat Prod 2014; 77: 1311–20.

113      Jung Y-J, Park J-H, Cho J-G, et al. Lignan and flavonoids from the stems of Zea mays and their anti-inflammatory and neuroprotective activities. Arch Pharm Res 2014. doi:10.1007/s12272-014-0387-4.

114      Zheng J, Piao MJ, Kim KC, et al. Americanin B protects cultured human keratinocytes against oxidative stress by exerting antioxidant effects. In Vitro Cell Dev Biol Anim 2014; 50: 766–77.

115      Liu J-X, Luo M-Q, Xia M, et al. Marine compound catunaregin inhibits angiogenesis through the modulation of phosphorylation of akt and eNOS in vivo and in vitro. Mar Drugs 2014; 12: 2790–801.

116      Draganescu D, Ibanescu C, Tamba BI, Andritoiu C V, Dodi G, Popa MI. Flaxseed lignan wound healing formulation: Characterization and in vivo therapeutic evaluation. Int J Biol Macromol 2015; 72: 614–23.

117      Mason JK, Thompson LU. Flaxseed and its lignan and oil components: can they play a role in reducing the risk of and improving the treatment of breast cancer? Appl Physiol Nutr Metab 2014; 39: 663–78.

118      Truan JS, Chen J-M, Thompson LU. Comparative effects of sesame seed lignan and flaxseed lignan in reducing the growth of human breast tumors (MCF-7) at high levels of circulating estrogen in athymic mice. Nutr Cancer 2012; 64: 65–71.

119      Mabrok HB, Klopfleisch R, Ghanem KZ, Clavel T, Blaut M, Loh G. Lignan transformation by gut bacteria lowers tumor burden in a gnotobiotic rat model of breast cancer. Carcinogenesis 2012; 33: 203–8.

120      Chen J, Saggar JK, Corey P, Thompson LU. Flaxseed and pure secoisolariciresinol diglucoside, but not flaxseed hull, reduce human breast tumor growth (MCF-7) in athymic mice. J Nutr 2009; 139: 2061–6.

121      Delman D, Kimler BF, Fabian CJ, Petroff BK. Secoisolariciresinol diglucoside (SDG, flaxseed lignan) improves biomarkers of early mammary gland cancer progression in a rat model of breast and ovarian cancer. Cancer Res 2013; 73: 185–185.

122      Sacco SM, Chen J, Ganss B, Thompson LU, Ward WE. Flaxseed enhances the beneficial effect of low-dose estrogen therapy at reducing bone turnover and preserving bone microarchitecture in ovariectomized rats. Appl Physiol Nutr Metab 2014; 39: 801–10.

123      Monteiro EMH, Chibli LA, Yamamoto CH, et al. Antinociceptive and anti-inflammatory activities of the sesame oil and sesamin. Nutrients 2014; 6: 1931–44.

124      Baluchnejadmojarad T, Roghani M, Jalali Nadoushan M-R, et al. The sesame lignan sesamin attenuates vascular dysfunction in streptozotocin diabetic rats: involvement of nitric oxide and oxidative stress. Eur J Pharmacol 2013; 698: 316–21.

125      Zanwar A, Hegde M, Bodhankar S. Cardioprotective effect of flax lignan concentrate and omega-3-fatty acid alone and in combination in ischemia/reperfusion injury in isolated rat heart. Atherosclerosis 2014; 235: e251.

126      Zanwar A a., Hegde M V., Bodhankar SL. Protective role of concomitant administration of flax lignan concentrate and omega-3-fatty acid on myocardial damage in doxorubicin-induced cardiotoxicity. Food Sci Hum Wellness 2013; 2: 29–38.

127      Pietrofesa R, Turowski J, Tyagi S, et al. Radiation mitigating properties of the lignan component in flaxseed. BMC Cancer 2013; 13: 179.

128      Jenab M, Thompson LU. The influence of flaxseed and lignans on colon carcinogenesis and beta-glucuronidase activity. Carcinogenesis 1996; 17: 1343–8.

129      Shousha W, El-mezayen HA, Abdul-halim SS, Elham A. Antioxidant effect of Flaxseed against liver Cirrhosis induced in Thioacetamide intoxicated rats. Egypt J Hosp Med 2013; 51: 448–60.

130      Lin Y, Yngve A, Lagergren J, Lu Y. A dietary pattern rich in lignans, quercetin and resveratrol decreases the risk of oesophageal cancer. Br J Nutr 2014; 112: 2002–9.

131      Sun Q, Wedick NM, Pan A, et al. Gut microbiota metabolites of dietary lignans and risk of type 2 diabetes: a prospective investigation in two cohorts of U.S. women. Diabetes Care 2014; 37: 1287–95.

132      Cardet J-C, Johns CB, Savage JH. Bacterial metabolites of diet-derived lignans and isoflavones inversely associate with asthma and wheezing. J Allergy Clin Immunol 2014. doi:10.1016/j.jaci.2014.07.035.

133      Zamora-Ros R, Sacerdote C, Ricceri F, et al. Flavonoid and lignan intake in relation to bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Br J Cancer 2014; 111: 1870–80.

134      Buck K, Zaineddin AK, Vrieling A, et al. Estimated enterolignans, lignan-rich foods, and fibre in relation to survival after postmenopausal breast cancer. Br J Cancer 2011; 105: 1151–7.

135      Velentzis LS, Cantwell MM, Cardwell C, Keshtgar MR, Leathem AJ, Woodside J V. Lignans and breast cancer risk in pre- and post-menopausal women: meta-analyses of observational studies. Br J Cancer 2009; 100: 1492–8.

136      Torres-Sanchez L, Galvan-Portillo M, Wolff MS, Lopez-Carrillo L. Dietary consumption of phytochemicals and breast cancer risk in Mexican women. Public Heal Nutr 2009; 12: 825–31.

137      Anderson LN, Cotterchio M, Boucher BA, Kreiger N. Phytoestrogen intake from foods, during adolescence and adulthood, and risk of breast cancer by estrogen and progesterone receptor tumor subgroup among Ontario women. Int J Cancer 2013; 132: 1683–92.

138      Guglielmini P, Rubagotti A, Boccardo F. Serum enterolactone levels and mortality outcome in women with early breast cancer: a retrospective cohort study. Breast Cancer Res Treat 2012; 132: 661–8.

139      McCann SE, Hootman KC, Weaver AM, et al. Dietary intakes of total and specific lignans are associated with clinical breast tumor characteristics. J Nutr 2012; 142: 91–8.

140      Lof M, Weiderpass E. Epidemiologic evidence suggests that dietary phytoestrogen intake is associated with reduced risk of breast, endometrial, and prostate cancers. Nutr Res 2006; 26: 609–19.

141      Dai Q, Franke AA, Jin F, et al. Urinary excretion of phytoestrogens and risk of breast cancer among Chinese women in Shanghai. Cancer Epidemiol Biomarkers Prev 2002; 11: 815–21.

142      Pietinen P, Stumpf K, Männistö S, Kataja V, Uusitupa M, Adlercreutz H. Serum enterolactone and risk of breast cancer: a case-control study in eastern Finland. Cancer Epidemiol Biomarkers Prev 2001; 10: 339–44.

143      Hultén K, Winkvist A, Lenner P, Johansson R, Adlercreutz H, Hallmans G. An incident case-referent study on plasma enterolactone and breast cancer risk. Eur J Nutr 2002; 41: 168–76.

144      Xie J, Tworoger SS, Franke A a, et al. Plasma enterolactone and breast cancer risk in the Nurses’ Health Study II. Breast Cancer Res Treat 2013. doi:10.1007/s10549-013-2586-y.

145      Kuijsten A, Arts ICW, Hollman PCH, van’t Veer P, Kampman E. Plasma enterolignans are associated with lower colorectal adenoma risk. Cancer Epidemiol Biomarkers Prev 2006; 15: 1132–6.

146      Cotterchio M, Boucher BA, Manno M, Gallinger S, Okey A, Harper P. Dietary phytoestrogen intake is associated with reduced colorectal cancer risk. J Nutr 2006; 136: 3046–53.

147      Johnsen NF, Olsen A, Thomsen BLR, et al. Plasma enterolactone and risk of colon and rectal cancer in a case-cohort study of Danish men and women. Cancer Causes Control 2010; 21: 153–62.

148      Ward HA, Kuhnle GGC, Mulligan AA, Lentjes MAH, Luben RN, Khaw K. Breast, colorectal, and prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition-Norfolk in relation to phytoestrogen intake derived from an improved database. Am J Clin Nutr 2010; 91: 440–8.

149      McCann MJ, Gill CIR, McGlynn H, Rowland IR. Role of mammalian lignans in the prevention and treatment of prostate cancer. Nutr Cancer 2005; 52: 1–14.

150      Demark-Wahnefried W, Price DT, Polascik TJ, et al. Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: exploring the effects on hormonal levels, prostate-specific antigen, and histopathologic features. Urology 2001; 58: 47–52.

151      Pellegrini N, Valtueña S, Ardigò D, et al. Intake of the plant lignans matairesinol, secoisolariciresinol, pinoresinol, and lariciresinol in relation to vascular inflammation and endothelial dysfunction in middle age-elderly men and post-menopausal women living in Northern Italy. Nutr Metab Cardiovasc Dis 2010; 20: 64–71.

152      Vanharanta M, Voutilainen S, Lakka TA, van der Lee M, Adlercreutz H, Salonen JT. Risk of acute coronary events according to serum concentrations of enterolactone: a prospective population-based case-control study. Lancet 1999; 354: 2112–5.

153      Vanharanta M, Voutilainen S, Rissanen TH, Adlercreutz H, Salonen JT. Risk of cardiovascular disease-related and all-cause death according to serum concentrations of enterolactone: Kuopio Ischaemic Heart Disease Risk Factor Study. Arch Intern Med 2003; 163: 1099–104.

154      Frankenfeld CL. Relationship of obesity and high urinary enterolignan concentrations in 6806 children and adults: analysis of National Health and Nutrition Examination Survey data. Eur J Clin Nutr 2013; : 1–3.

155      Saxena S, Katare C. Evaluation of flaxseed formulation as a potential therapeutic agent in mitigation of dyslipidemia. Biomed J 2014; 37: 386–90.

156      Wong H, Chahal N, Manlhiot C, Niedra E, McCrindle BW. Flaxseed in Pediatric Hyperlipidemia: A Placebo-Controlled, Blinded, Randomized Clinical Trial of Dietary Flaxseed Supplementation for Children and Adolescents With Hypercholesterolemia. JAMA Pediatr 2013; : 1–5.

157      Almario RU, Karakas SE. Lignan content of the flaxseed influences its biological effects in healthy men and women. J Am Coll Nutr 2013; 32: 194–9.

158      Thompson LU, Chen JM, Li T, Strasser-Weippl K, Goss PE. Dietary flaxseed alters tumor biological markers in postmenopausal breast cancer. Clin Cancer Res 2005; 11: 3828–35.

159      Bylund A, Lundin E, Zhang JX, et al. Randomised controlled short-term intervention pilot study on rye bran bread in prostate cancer. Eur J Cancer Prev 2003; 12: 407–15.

160      Shousha W, El-mezayen HA, Abdul-halim SS, Elham A. Effect of whole and ground Salba seeds (Salvia Hispanica L.) on postprandial glycemia in healthy volunteers: a randomized controlled, dose-response trial. Eur J Clin Nutr 2013; 2009: 1–3.

161      Gao J, Hattori M. Metabolic activation of lignans to estrogenic and antiestrogenic substances by human intestinal bacteria. J Tradit Med 2005; 22: 213–21.

162      Saleem M, Kim HJ, Ali MS, Lee YS. An update on bioactive plant lignans. Nat Prod Rep 2005; 22: 696–716.

163      Dixon R a. Phytoestrogens. Annu Rev Plant Biol 2004; 55: 225–61.

164      Xia Y, Chen M, Zhu P, et al. Urinary phytoestrogen levels related to idiopathic male infertility in Chinese men. Env Int 2013; 59: 161–7.

165      Jackson MD, McFarlane-Anderson ND, Simon GA, Bennett FI, Walker SP. Urinary phytoestrogens and risk of prostate cancer in Jamaican men. Cancer Causes Control 2010; 21: 2249–57.

166      Ward HA, Kuhnle GGC. Phytoestrogen consumption and association with breast, prostate and colorectal cancer in EPIC Norfolk. Arch Biochem Biophys 2010; 501: 170–5.



A version of this post appears on the Vital Juice blog.
photo (1)

What is the one nutritional fact that you know about carrots? If you’re like most people you will answer that is has a lot of beta-carotene. This is true. You might also be aware that beta-carotene plays some kind of role in eye function. This is also true. But carrots and carotenoids do far more than that. Settle in with some freshly made carrot juice and hear all about the benefits of carotenoids.

Beta-carotene is part of a class of compounds called carotenoids that play many different roles in the body. Carotenoids are molecules that are responsible for a great majority of the yellow to red colors that we see and have a wide range of functions in the natural world, from light-harvesting pigments to protecting chloroplasts from reactive oxygen to cell-to-cell communication to their prominent role in the structure of eyes (Figure 1).1,2 Carrots are excellent sources of carotenoids, mostly in the form of alpha and beta-carotene.3,4 Carotenoids may be best known for their role as a precursor to vitamin A, but beyond that carotenoids have been shown to be associated with a wide range of beneficial properties.

Figure 1. Carotenoids in Nature from Von Lintig, J. & Sies, H. (2013)

Figure 1. Carotenoids in Nature from Von Lintig, J. & Sies, H. (2013)


One of the major roles of carotenoids is that many of them can be converted into vitamin A by enzymes within the body. This is why carotenoids like beta-carotene are sometimes called “pre-vitamin A” or “pro-vitamin A.” It is important to realize that carotenoids like beta-carotene, while very similar, are not the same thing as vitamin A. This is actually a very good thing. Let me explain… Although your body needs vitamin A to function optimally, ingesting too much vitamin A is highly toxic to the body and can cause all sorts of problems. If you want to learn about it in more detail visit the Wikipedia page on hypervitaminosis A, but some of the problems include weakness, nausea, bone fractures, hair loss, and fetal deformation if taken while pregnant. However, you can essentially eat or drink all the beta-carotene you want and be completely fine. The worst that can happen is that if you consume quite a bit then your body will begin storing the carotenoids in your skin making you appear slightly orange, but this condition is completely benign and might even save you from fake-baking to get a tan. The body will then selectively convert the stored carotenoids into vitamin A when it is needed.

Carotenoids and Cancer

Carotenoids, especially lycopene, have been associated with a lower risk of prostate cancer in several studies.5–12 The evidence regarding the link between carotenoids and lung cancer is mixed. While some earlier studies in the 1990s suggested that carotenoids increase the risk of lung cancer in heavy smokers13,14 newer reports suggest the opposite.15–17 Nevertheless, epidemiological evidence suggests that a diet rich in carotenoids is generally protective against breast and other cancers.18–24

Other Benefits of Carotenoids

Because of their role in eye health, carotenoids have been shown to be protective of age-related macular degeneration (AMD) as well as generally increasing visual acuity.10,25–31 There is also evidence that carotenoids help prevent skin damage from ultraviolet light.32–35

If you’d like to know more about carotenoids and their benefits, check out the Linus Pauling Institute’s page on the subject. LPI is actually a fantastic evidence-based resource on all kinds of phytochemicals, minerals, vitamins, and other important issues relating to nutrition.



  1. Von Lintig, J. & Sies, H. Carotenoids. Arch. Biochem. Biophys. 539, 99–101 (2013).
  2. King, A. & Young, G. Characteristics and occurrence of phenolic phytochemicals. J. Am. Diet. Assoc. 99, 213–8 (1999).
  3. Heinonen, M. I., Ollilainen, V., Linkola, E. K., Varo, P. T. & Koivistoinen, P. E. Carotenoids in Finnish foods: vegetables, fruits, and berries. J. Agric. Food Chem. 37, 655–659 (1989).
  4. Holden, J. M. et al. Carotenoid Content of U.S. Foods: An Update of the Database. J. Food Compos. Anal. 12, 169–196 (1999).
  5. Zu, K. et al. Dietary lycopene, angiogenesis, and prostate cancer: a prospective study in the prostate-specific antigen era. J. Natl. Cancer Inst. 106, djt430 (2014).
  6. Umesawa, M. et al. Relationship between vegetable and carotene intake and risk of prostate cancer: the JACC study. Br. J. Cancer 110, 792–6 (2014).
  7. Donaldson, M. S. A carotenoid health index based on plasma carotenoids and health outcomes. Nutrients 3, 1003–22 (2011).
  8. Rao, A. V & Rao, L. G. Carotenoids and human health. Pharmacol. Res. 55, 207–16 (2007).
  9. Tanaka, T., Shnimizu, M. & Moriwaki, H. Cancer chemoprevention by carotenoids. Molecules 17, 3202–42 (2012).
  10. Stahl, W. & Sies, H. Bioactivity and protective effects of natural carotenoids. Biochim. Biophys. Acta 1740, 101–7 (2005).
  11. Margalit, D. N. et al. Beta-carotene antioxidant use during radiation therapy and prostate cancer outcome in the Physicians’ Health Study. Int. J. Radiat. Oncol. Biol. Phys. 83, 28–32 (2012).
  12. Gann, P. H. et al. Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective analysis. Cancer Res. 59, 1225–30 (1999).
  13. Albanes, D. et al. Effects of alpha-tocopherol and beta-carotene supplements on cancer incidence in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study. Am. J. Clin. Nutr. 62, 1427S–1430S (1995).
  14. Albanes, D. et al. Alpha-Tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance. J. Natl. Cancer Inst. 88, 1560–70 (1996).
  15. Min, K.-B. & Min, J.-Y. Serum carotenoid levels and lung cancer mortality risk in US adults. Cancer Sci. (2014). doi:10.1111/cas.12405
  16. Männistö, S. et al. Dietary carotenoids and risk of lung cancer in a pooled analysis of seven cohort studies. Cancer Epidemiol Biomarkers Prev 13, 40–8 (2004).
  17. Shardell, M. D. et al. Low-serum carotenoid concentrations and carotenoid interactions predict mortality in US adults: the Third National Health and Nutrition Examination Survey. Nutr. Res. 31, 178–89 (2011).
  18. Donaldson, M. S. Nutrition and cancer: a review of the evidence for an anti-cancer diet. Nutr. J. 3, 19 (2004).
  19. Mignone, L. I. et al. Dietary carotenoids and the risk of invasive breast cancer. Int. J. Cancer 124, 2929–37 (2009).
  20. Wang, L. et al. Specific carotenoid intake is inversely associated with the risk of breast cancer among Chinese women. Br. J. Nutr. 1–10 (2014). doi:10.1017/S000711451300411X
  21. Rock, C. L. et al. Longitudinal biological exposure to carotenoids is associated with breast cancer-free survival in the Women’s Healthy Eating and Living Study. Cancer Epidemiol Biomarkers Prev 18, 486–94 (2009).
  22. Aune, D. et al. Dietary compared with blood concentrations of carotenoids and breast cancer risk: a systematic review and meta-analysis of prospective studies. Am. J. Clin. Nutr. 96, 356–73 (2012).
  23. Bolhassani, A., Khavari, A. & Bathaie, S. Z. Saffron and natural carotenoids: Biochemical activities and anti-tumor effects. Biochim. Biophys. Acta 1845, 20–30 (2014).
  24. Kabat, G. C. et al. Longitudinal study of serum carotenoid, retinol, and tocopherol concentrations in relation to breast cancer risk among postmenopausal women. Am. J. Clin. Nutr. 90, 162–9 (2009).
  25. Beatty, S. et al. Secondary outcomes in a clinical trial of carotenoids with coantioxidants versus placebo in early age-related macular degeneration. Ophthalmology 120, 600–6 (2013).
  26. Hammond, B. R. & Fletcher, L. M. Influence of the dietary carotenoids lutein and zeaxanthin on visual performance: application to baseball. Am. J. Clin. Nutr. 96, 1207S–13S (2012).
  27. Meyers, K. J. et al. Genetic evidence for role of carotenoids in age-related macular degeneration in the Carotenoids in Age-Related Eye Disease Study (CAREDS). Invest. Ophthalmol. Vis. Sci. 55, 587–99 (2014).
  28. Piermarocchi, S. et al. Carotenoids in Age-related Maculopathy Italian Study (CARMIS): two-year results of a randomized study. Eur. J. Ophthalmol. 22, 216–25
  29. Sabour-Pickett, S., Nolan, J. M., Loughman, J. & Beatty, S. A review of the evidence germane to the putative protective role of the macular carotenoids for age-related macular degeneration. Mol. Nutr. Food Res. 56, 270–86 (2012).
  30. Abdel-Aal, E.-S. M., Akhtar, H., Zaheer, K. & Ali, R. Dietary sources of lutein and zeaxanthin carotenoids and their role in eye health. Nutrients 5, 1169–85 (2013).
  31. Ros, M. M. et al. Plasma carotenoids and vitamin C concentrations and risk of urothelial cell carcinoma in the European Prospective Investigation into Cancer and Nutrition. Am. J. Clin. Nutr. 96, 902–10 (2012).
  32. Meinke, M. C. et al. Influence of dietary carotenoids on radical scavenging capacity of the skin and skin lipids. Eur. J. Pharm. Biopharm. 84, 365–73 (2013).
  33. Böhm, F., Edge, R. & Truscott, T. G. Interactions of dietary carotenoids with singlet oxygen (1O2) and free radicals: potential effects for human health. Acta Biochim. Pol. 59, 27–30 (2012).
  34. Yoshihisa, Y., Rehman, M. U. & Shimizu, T. Astaxanthin, a xanthophyll carotenoid, inhibits ultraviolet-induced apoptosis in keratinocytes. Exp. Dermatol. 23, 178–83 (2014).
  35. Bouilly-Gauthier, D. et al. Clinical evidence of benefits of a dietary supplement containing probiotic and carotenoids on ultraviolet-induced skin damage. Br. J. Dermatol. 163, 536–43 (2010).


The Beauty of the Beet

A version of this post appears in the Vital Juice blog.

If you enjoy a healthy and active lifestyle like most people who are into nutrition like me, you may have ventured into a nutrition supplement store to pick up some powder or pills that might help your athletic performance or boost your immune system. One particular supplement that is popular among weight lifters and body builders is nitric oxide (NO). The reason it is popular is that nitric oxide is a very cool molecule that helps to dilate blood vessels. For athletes and body builders this can mean increased blood flow (and therefore increased oxygen and nutrients) to tissues. Nitric oxide can also be used by people trying to lower their blood pressure or trying to prevent a myocardial infarction. It is such a cool molecule that it was even named “Molecule of the Year” by the journal Science.1 Drs. Robert F. Furchgott, Louis J. Ignarro, and Ferid Murad even won Nobel Prizes for their research into nitric oxide.2

However, if you venture into a supplement store you will find nitric oxide products for purchase, and they will all be overpriced. Further, dietary supplements are not required to provide proof of safety and effectiveness to the FDA prior to marketing, so there’s really no telling what is in there, how safe it is, and if it even works. Not only that but most of these NO supplements contain caffeine, which is a vasoconstrictor, essentially countering the effects of the nitric oxide. But did you know that there is another source of NO? It’s called beet juice. It’s true. Beet juice contains quite a bit of inorganic nitrate which is then converted to NO in the body.3 So much so that when scientific researchers want to study the effects of NO, instead of buying NO supplements to give their study participants they simply give them beet juice.


Let’s take a look at the research behind beet juice and exercise…

A very recent study by Bond et al. published in the journal Applied Physiology, Nutrition, and Metabolism indicates that beet juice does in fact substantially increase the amount of NO in the blood.4 The researchers then studied the effects of drinking beet juice before aerobic exercise and found that those that drank beet juice performed better than those who did not.

beet graph

This is not an unusual result. Other exercise researchers have done similar studies and had similar findings.5–17 This recent study, for example, from the Journal of Applied Physiology indicated that beetroot juice (BR) is better than placebo (PL) at increasing the time to failure and decreasing VO2 max.6 VO2 max is a common measurement used to indicate how hard your lungs are working when you exercise, but the long and the short of it is that a lower VO2 max is better.

beet graph 2

As I mentioned earlier, NO is not just beneficial for athletes. There is quite a bit of evidence that beet juice significantly reduces hypertension (also known as high blood pressure), which is a serious risk factor for cardiovascular diseases.3,17–23

Of course improving risk factors for heart disease and helping gym rats make those gains is not the only thing this magical root can do. In addition to inorganic nitrate, beets contain a number of bioactive compounds called, betaines, betalains, and betanins, the latter of which are what give the beets their distinctive color. So what exactly do these compounds do? Scientists have been looking into them recently and have found some very promising results.

Beet Helps to Protect the Liver

Betaine is a lipotrope, which is something that helps shuttle fat outside the liver and facilitate fat metabolism. This prevents fat from accumulating in the liver and can help prevent non-alcaholic fatty liver disease.24 Betaine also helps to protect the liver when alcohol is involved as well.25 In fact there are many, many animal studies and cell culture studies that suggest that beet compounds like betaine and betanin are very effective at protecting the liver from many types of damage.26–31

How does that happen? It’s a powerful combination of two factors: 1) These compounds are powerful antioxidants that help to prevent oxidative damage to cells, and 2) they help to up-regulate the expression of other enzymes that play a role in removing harmful compounds from the body.32–35

But there are not just results from animal and cell studies, there are results from human studies as well. Promising results that show that beet compounds are associated with a reduced risk of cancer.36–39

Betaine is an Osmolyte

A normal, healthy cell must maintain a very specific osmotic balance between the water in the cell and electrolytes like sodium, potassium, and other minerals. Betaine helps to facilitate this balance by maintaining cellular hydration at an optimal state.24,36 In other words, it helps prevent the cell from becoming dehydrated.

In short, like my father always says, “You can’t beat the beets!”


beet juice

photo by Zsuzsanna Kilian

  1. Koshland, D. The molecule of the year. Science (80-. ). 258, 1861–1861 (1992).
  2. The Nobel Prize in Physiology or Medicine 1998. at <>
  3. Webb, A. J. et al. Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite. Hypertension 51, 784–90 (2008).
  4. Bond, V., Curry, B. H., Adams, R. G., Millis, R. M. & Haddad, G. E. Cardiorespiratory function associated with dietary nitrate supplementation. Appl. Physiol. Nutr. Metab. 39, 168–72 (2014).
  5. Pinna, M. et al. Effect of beetroot juice supplementation on aerobic response during swimming. Nutrients 6, 605–15 (2014).
  6. Wylie, L. J. et al. Beetroot juice and exercise: pharmacodynamic and dose-response relationships. J. Appl. Physiol. 115, 325–36 (2013).
  7. Haider, G. & Folland, J. P. Nitrate Supplementation Enhances the Contractile Properties of Human Skeletal Muscle. Med. Sci. Sports Exerc. (2014). doi:10.1249/MSS.0000000000000351
  8. Thompson, K. G. et al. Influence of dietary nitrate supplementation on physiological and cognitive responses to incremental cycle exercise. Respir. Physiol. Neurobiol. 193, 11–20 (2014).
  9. Breese, B. C. et al. Beetroot juice supplementation speeds O2 uptake kinetics and improves exercise tolerance during severe-intensity exercise initiated from an elevated metabolic rate. Am. J. Physiol. 305, R1441–50 (2013).
  10. Hoon, M. W. et al. The Effect of Variable Doses of Inorganic Nitrate-Rich Beetroot Juice on Simulated 2,000 m Rowing Performance in Trained Athletes. Int. J. Sports Physiol. Perform. (2013). at <>
  11. Muggeridge, D. J. et al. The effects of a single dose of concentrated beetroot juice on performance in trained flatwater kayakers. Int. J. Sport Nutr. Exerc. Metab. 23, 498–506 (2013).
  12. Muggeridge, D. J. et al. A single dose of beetroot juice enhances cycling performance in simulated altitude. Med. Sci. Sports Exerc. 46, 143–50 (2014).
  13. Kelly, J., Vanhatalo, A., Wilkerson, D. P., Wylie, L. J. & Jones, A. M. Effects of nitrate on the power-duration relationship for severe-intensity exercise. Med. Sci. Sports Exerc. 45, 1798–806 (2013).
  14. Jones, A. M., Bailey, S. J. & Vanhatalo, A. Dietary nitrate and O₂ consumption during exercise. Med. Sport Sci. 59, 29–35 (2012).
  15. Ferguson, S. K. et al. Impact of dietary nitrate supplementation via beetroot juice on exercising muscle vascular control in rats. J. Physiol. 591, 547–57 (2013).
  16. Lansley, K. E. et al. Dietary nitrate supplementation reduces the O2 cost of walking and running: a placebo-controlled study. J. Appl. Physiol. 110, 591–600 (2011).
  17. Vanhatalo, A. et al. Acute and chronic effects of dietary nitrate supplementation on blood pressure and the physiological responses to moderate-intensity and incremental exercise. Am. J. Physiol. Regul. Integr. Comp. Physiol. 299, R1121–31 (2010).
  18. Siervo, M., Lara, J., Ogbonmwan, I. & Mathers, J. C. Inorganic nitrate and beetroot juice supplementation reduces blood pressure in adults: a systematic review and meta-analysis. J. Nutr. 143, 818–26 (2013).
  19. Coles, L. T. & Clifton, P. M. Effect of beetroot juice on lowering blood pressure in free-living, disease-free adults: a randomized, placebo-controlled trial. Nutr. J. 11, 106 (2012).
  20. Hobbs, D. A., Kaffa, N., George, T. W., Methven, L. & Lovegrove, J. A. Blood pressure-lowering effects of beetroot juice and novel beetroot-enriched bread products in normotensive male subjects. Br. J. Nutr. 108, 2066–74 (2012).
  21. Ferreira, L. F. & Behnke, B. J. A toast to health and performance! Beetroot juice lowers blood pressure and the O2 cost of exercise. J. Appl. Physiol. 110, 585–6 (2011).
  22. Kenjale, A. A. et al. Dietary nitrate supplementation enhances exercise performance in peripheral arterial disease. J. Appl. Physiol. 110, 1582–91 (2011).
  23. Kapil, V. et al. Inorganic nitrate supplementation lowers blood pressure in humans: role for nitrite-derived NO. Hypertension 56, 274–81 (2010).
  24. Craig, S. A. S. Betaine in human nutrition. Am. J. Clin. Nutr. 80, 539–49 (2004).
  25. Barak, A., Beckenhauer, H. C. & Tuma, D. J. Betaine, ethanol, and the liver: a review. Alcohol 13, 395–8 (1996).
  26. Jung, G.-Y. et al. Betaine Alleviates Hypertriglycemia and Tau Hyperphosphorylation in db/db Mice. Toxicol. Res. 29, 7–14 (2013).
  27. Krajka-Kuźniak, V., Paluszczak, J., Szaefer, H. & Baer-Dubowska, W. Betanin, a beetroot component, induces nuclear factor erythroid-2-related factor 2-mediated expression of detoxifying/antioxidant enzymes in human liver cell lines. Br. J. Nutr. 110, 2138–49 (2013).
  28. Krajka-Kuźniak, V., Szaefer, H., Ignatowicz, E., Adamska, T. & Baer-Dubowska, W. Beetroot juice protects against N-nitrosodiethylamine-induced liver injury in rats. Food Chem. Toxicol. 50, 2027–33 (2012).
  29. Szaefer, H., Krajka-Kuźniak, V., Ignatowicz, E., Adamska, T. & Baer-Dubowska, W. Evaluation of the effect of beetroot juice on DMBA-induced damage in liver and mammary gland of female Sprague-Dawley rats. Phyther. Res. 28, 55–61 (2014).
  30. Váli, L. et al. Liver-protecting effects of table beet (Beta vulgaris var. rubra) during ischemia-reperfusion. Nutrition 23, 172–8 (2007).
  31. Sakihama, Y., Maeda, M., Hashimoto, M., Tahara, S. & Hashidoko, Y. Beetroot betalain inhibits peroxynitrite-mediated tyrosine nitration and DNA strand cleavage. Free Radic. Res. 46, 93–9 (2012).
  32. Lee, C.-H., Wettasinghe, M., Bolling, B. W., Ji, L.-L. & Parkin, K. L. Betalains, phase II enzyme-inducing components from red beetroot (Beta vulgaris L.) extracts. Nutr. Cancer 53, 91–103 (2005).
  33. Wettasinghe, M., Bolling, B., Plhak, L., Xiao, H. & Parkin, K. Phase II enzyme-inducing and antioxidant activities of beetroot (Beta vulgaris L.) extracts from phenotypes of different pigmentation. J. Agric. Food Chem. 50, 6704–9 (2002).
  34. Gandía-Herrero, F., Escribano, J. & García-Carmona, F. Purification and antiradical properties of the structural unit of betalains. J. Nat. Prod. 75, 1030–6 (2012).
  35. Georgiev, V. G. et al. Antioxidant activity and phenolic content of betalain extracts from intact plants and hairy root cultures of the red beetroot Beta vulgaris cv. Detroit dark red. Plant Foods Hum. Nutr. 65, 105–11 (2010).
  36. Ueland, P. M. Choline and betaine in health and disease. J. Inherit. Metab. Dis. 34, 3–15 (2011).
  37. Ying, J. et al. Associations between dietary intake of choline and betaine and lung cancer risk. PLoS One 8, e54561 (2013).
  38. Xu, X. et al. High intakes of choline and betaine reduce breast cancer mortality in a population-based study. FASEB J. 23, 4022–8 (2009).
  39. Zielińska-Przyjemska, M., Olejnik, A., Dobrowolska-Zachwieja, A. & Grajek, W. In vitro effects of beetroot juice and chips on oxidative metabolism and apoptosis in neutrophils from obese individuals. Phyther. Res. 23, 49–55 (2009).