LeClaire Institute

Module 3 · Bioactives

Bioactives are compounds in food that are not essential nutrients but still act on the body: polyphenols such as flavonoids, carotenoids, phytosterols, the sulfur compounds of broccoli and garlic, the pungent compounds of chili, pepper and ginger, and the stimulants caffeine and theobromine. Each is shown in ball-and-stick form with what it does, the cautions, and where it is found. The figure is on the left and the lesson script on the right; the quiz is at the end.

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Figure 1

The Bioactives Family Tree

Plant compounds that are not essential nutrients, in four families.

What the tree shows
Not nutrients, but activeBioactives are compounds in food that are not essential nutrients, so there is no deficiency disease and usually no recommended intake, but they still act on the body. Most come from plants, which make them as pigments, defenses or signals.
Four chemical familiesPolyphenols are built on rings with OH groups. Terpenoids are built from five-carbon isoprene units. The sulfur compounds give the cabbage and onion families their bite. And the spice and stimulant compounds act on nerve receptors.
Whole foods firstDiets rich in fruit, vegetables, tea, coffee, whole grains and legumes are consistently linked to better health. Isolated bioactives in pills have mostly not matched those results, and a few have backfired.
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Figure 2

Flavonoids

What a phenol is, and three flavonoids: quercetin, anthocyanins and isoflavones.

Starting point

What “phenol” means

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  1. 1A phenol is an OH group on a benzene ring. A polyphenol has several of them. That OH easily gives up its hydrogen to quench a reactive molecule, which is why polyphenols are antioxidants in a test tube.
Flavonoids

Quercetin, a flavonol

234
  1. 2Every flavonoid has the same fifteen-carbon skeleton: a ring here…
  2. 3…a ring here, and a middle ring with an oxygen joining them.
  3. 4Two neighboring OH groups on this ring make it a strong antioxidant and metal binder.

What it is: Flavonoids are the largest group of polyphenols, with thousands of kinds; quercetin is the most common flavonol in food.

In your body: Little is absorbed intact; most is changed by the liver and gut bacteria, and the products may calm inflammation and help blood vessels relax. Diets high in flavonoid-rich foods are linked to lower risk of heart disease and stroke, though effects of single flavonoids are unproven.

Too much: There is no deficiency. Food amounts are safe; high-dose supplements can interact with some medicines.

Found in: Onions (especially red), kale, apples with the skin, capers, berries, broccoli, tea, red wine. Cocoa, tea and apples are rich in the related flavanols (catechins; see Antinutrients).

Cyanidin, an anthocyanin color

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  1. 5In anthocyanins the middle ring’s oxygen carries a positive charge, making the whole ring system a pigment.
  2. 6In food a sugar is attached here; the sugar-bound form is an anthocyanin.

What it is: Anthocyanins are the red, purple and blue pigments of berries, red cabbage and grapes. Their color changes with acidity: red in acid, purple near neutral, blue-green in alkali, which is why red cabbage turns blue when cooked with baking soda.

In your body: Studies link berry-rich diets to better blood vessel function and blood pressure; anthocyanins are thought to be part of the reason.

Found in: Blueberries, blackberries, black currants, cherries, red grapes, red cabbage, purple sweet potatoes, eggplant skin, black beans. The EU allows them as a natural coloring (E163).

Genistein, an isoflavone

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  1. 7In isoflavones the second ring is attached one carbon over…
  2. 8…which puts its OH about as far from the other end as in estrogen, so genistein weakly fits estrogen receptors.

What it is: Isoflavones are the main phytoestrogens: plant compounds that act like a weak estrogen.

In your body: In Asian populations that eat soy often, soy intake is linked to lower rates of some cancers and heart disease, and soy foods may modestly ease hot flashes. Normal intake of soy foods is considered safe, including for breast cancer survivors, by major cancer organizations.

Too much: High-dose isoflavone supplements are less studied than soy foods; anyone with a hormone-sensitive condition should ask a clinician.

Found in: Soybeans, edamame, tofu, tempeh, miso and soy milk; small amounts in chickpeas and other legumes.

carbon hydrogen oxygen · every molecule on this page is drawn at the same scale with every hydrogen shown · tap one to enlarge it

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Figure 3

Other Polyphenols

Resveratrol, chlorogenic acid in coffee, and hydroxytyrosol in olive oil.

Resveratrol

Resveratrol, a stilbene

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  1. 1Two phenol rings joined by a double bond. Grapes make it in their skins to fight fungal infection.

What it is: A polyphenol made by grapes, peanuts and some berries in response to stress or infection.

In your body: It extended lifespan in yeast and some animals and drew attention as a reason for the “French paradox”, but human trials have been disappointing, and the amount in a glass of red wine is tiny, far below the doses used in research.

Too much: No deficiency. High-dose supplements can cause digestive upset and may interact with blood thinners.

Found in: Red grape skins and red wine, peanuts, pistachios, blueberries, cranberries, cocoa.

Chlorogenic acid

Chlorogenic acid

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  1. 2A ring of carbons with OH groups (quinic acid)…
  2. 3…joined through an ester link…
  3. 4…to caffeic acid, the phenol part, with two OH groups side by side.

What it is: A phenolic acid; the main polyphenol in coffee, where it adds bitterness and acidity.

In your body: Coffee is the largest source of polyphenols for many adults, and moderate coffee drinking is linked to lower risk of type 2 diabetes and liver disease; chlorogenic acid may contribute by slowing sugar absorption. Roasting breaks much of it down, so light roasts keep more.

Found in: Coffee (green beans have the most), apples, pears, blueberries, eggplant, potatoes, artichokes, sunflower seeds.

Hydroxytyrosol

Hydroxytyrosol

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  1. 5Two neighboring OH groups on one ring, the same strong antioxidant grip as quercetin and caffeic acid.

What it is: The main polyphenol of olives and extra-virgin olive oil, along with its relatives tyrosol and oleuropein; part of the bitter, peppery bite of fresh oil.

In your body: The EU allows the claim that olive oil polyphenols help protect blood lipids from oxidation, for oils providing at least 5 mg of hydroxytyrosol and its relatives per 20 g of oil. It is one reason extra-virgin oil is thought to do more than refined olive oil.

Found in: Extra-virgin olive oil (refining removes most of it), table olives, olive leaves.

carbon hydrogen oxygen · every molecule on this page is drawn at the same scale with every hydrogen shown · tap one to enlarge it

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Figure 4

Carotenoids

Isoprene chains that color food orange and red.

Starting point

The building block

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  1. 1Terpenoids are built from isoprene, a five-carbon unit with one branch. Eight of them make a carotenoid; six make squalene, which cells fold into the sterols in Figure 5.
Carotenoids

β-Carotene, C₄₀H₅₆

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  1. 2A ring at each end…
  2. 3…joined by a long chain of alternating double and single bonds. That chain absorbs blue light, so it looks orange.
  3. 4Cut in the middle, it makes two molecules of vitamin A (see Fat-Soluble Vitamins).

What it is: The best-known carotenoid and the main provitamin A in plants.

In your body: Your gut turns some of it into vitamin A, as needed, so it does not cause vitamin A poisoning. It is also an antioxidant in the fat of cell membranes. It is absorbed far better from cooked food eaten with some fat.

Too much: Eating a lot can turn the skin yellow-orange (carotenemia), which is harmless and fades. High-dose beta-carotene supplements raised lung cancer risk in smokers in two large trials, so smokers should avoid them.

Found in: Carrots, sweet potatoes, pumpkin and winter squash, spinach, kale, cantaloupe, mangoes, apricots, red palm oil.

Lycopene, C₄₀H₅₆

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  1. 5Lycopene has the same formula as beta-carotene, but its ends stay open instead of closing into rings…
  2. 6…and its chain of alternating double bonds lies flat from end to end, which shifts its color to red.

What it is: The red pigment of tomatoes and watermelon. It is not turned into vitamin A.

In your body: One of the strongest carotenoid antioxidants. Diets high in tomato products are linked to lower prostate cancer risk in some studies, though the evidence is mixed. Cooking and a little fat make it several times more available, so tomato sauce supplies more than raw tomatoes.

Found in: Tomatoes and tomato products (paste, sauce, ketchup), watermelon, pink grapefruit, guava, papaya.

Two more carotenoids
Lutein and zeaxanthinThese yellow carotenoids collect in the macula of the eye, where they filter blue light. In a large US trial (AREDS2), they helped slow advanced age-related macular degeneration in people who already had it. Kale, spinach, corn and egg yolk are good sources.

carbon hydrogen · every molecule on this page is drawn at the same scale with every hydrogen shown · tap one to enlarge it

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Figure 5

Phytosterols

The plant twin of cholesterol, which blocks its absorption.

Phytosterols

Cholesterol and its plant twin

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CholesterolC₂₇H₄₆O · animals

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β-SitosterolC₂₉H₅₀O · plants

  1. 1Cholesterol, the animal sterol: four fused rings, an OH, and a carbon tail (see Lipids).
  2. 2β-Sitosterol, the main plant sterol, is the same molecule with two extra carbons on the tail.

What it is: Phytosterols are the plant versions of cholesterol; plant stanols are the same with no double bond in the ring.

In your body: They look enough like cholesterol to crowd it out of the bile mixtures that carry it into gut cells, so less cholesterol is absorbed, both from food and from the cholesterol your liver sends into the gut. About 2 g a day lowers LDL cholesterol by roughly 8–10% within a few weeks; the US FDA and EU allow heart-health claims on foods with added sterols or stanols.

Too much: Very little is absorbed. People with the rare inherited disorder sitosterolemia absorb them and should avoid them. Large amounts can slightly lower beta-carotene absorption.

Found in: Vegetable oils (corn, canola, sesame), nuts, seeds, wheat germ, legumes. A normal diet supplies about 0.2–0.5 g a day; reaching 2 g needs fortified spreads, yogurts or drinks.

carbon hydrogen oxygen · every molecule on this page is drawn at the same scale with every hydrogen shown · tap one to enlarge it

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Figure 6

Sulforaphane and Allicin

The sulfur compounds of broccoli and garlic, made when you cut them.

Sulforaphane

From glucosinolate to sulforaphane

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GlucoraphaninC₁₂H₂₃NO₁₀S₃

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SulforaphaneC₆H₁₁NOS₂

  1. 1Broccoli stores glucoraphanin, a glucosinolate: a sulfur chain parked on a glucose…
  2. 2…with this sulfur-oxygen end that sulforaphane keeps.
  3. 3When the plant is cut or chewed, the enzyme myrosinase cuts off the glucose and the molecule rearranges into an N=C=S group: an isothiocyanate.

What it is: Glucosinolates are the sulfur defense compounds of the cabbage family; sulforaphane is the isothiocyanate made from broccoli’s main one. The sharp taste of mustard, horseradish, wasabi and radish comes from related isothiocyanates.

In your body: Sulforaphane switches on Nrf2, a cell signal that raises the body’s own detoxifying and antioxidant enzymes. Diets high in brassicas are linked to lower risk of some cancers; human trials of sulforaphane itself are small and early.

Too much: Normal amounts are safe; very large raw amounts can act as goitrogens when iodine is low (see Antinutrients).

Found in: Broccoli sprouts (by far the most), broccoli, Brussels sprouts, cabbage, kale, cauliflower, arugula, watercress.

Getting the most sulforaphane
  1. Chop or chewcutting brings glucosinolate and myrosinase together
  2. Wait or eat rawraw or lightly steamed broccoli keeps the enzyme working
  3. Boil harddestroys myrosinase; gut bacteria then convert only a little
  4. Rescuea pinch of mustard powder on cooked broccoli adds fresh myrosinase

Allicin, from garlic

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  1. 4Two sulfurs side by side, one with an oxygen. Allicin is made in seconds when garlic is crushed, as the enzyme alliinase meets its precursor alliin.

What it is: The pungent compound of freshly crushed garlic. It is unstable and soon breaks down into other sulfur compounds that carry garlic’s smell.

In your body: Garlic’s sulfur compounds kill microbes in the lab and may slightly lower blood pressure and cholesterol; the evidence for garlic supplements is modest and mixed. Letting crushed garlic stand a few minutes before heating is often advised, since heat stops alliinase.

Too much: Large amounts can upset the stomach, cause garlic breath and body odor, and add to the effect of blood thinners.

Found in: Garlic; onions, leeks, shallots and chives make related compounds, including the one that makes you cry when you cut onions.

carbon hydrogen oxygen nitrogen sulfur · every molecule on this page is drawn at the same scale with every hydrogen shown · tap one to enlarge it

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Figure 7

Capsaicin and Other Pungent Compounds

Chili, black pepper and ginger, and why they feel hot.

Capsaicin

Capsaicin

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  1. 1A vanilla-like head: a ring with OH and methoxy groups, like the vanillin in Flavorings…
  2. 2…an amide link…
  3. 3…and a fatty tail, which is why capsaicin dissolves in fat and milk, not water.

What it is: The compound that makes chili peppers hot; the Scoville scale measures it. Plants make it to deter mammals, while birds, which spread the seeds, cannot taste it.

In your body: Capsaicin switches on TRPV1, the nerve receptor that senses dangerous heat, so the mouth feels burning without any real burn. With repeated exposure the nerves become less sensitive, which is why capsaicin creams are used for pain. It slightly raises energy use, too little to matter for weight.

Too much: Very hot peppers can cause pain, vomiting and, rarely, chest pain. Milk and other fatty foods relieve the burn better than water.

Found in: Chili peppers, from mild jalapeños to habaneros and hotter; concentrated in the white ribs, not the seeds themselves. Bell peppers have essentially none.

Piperine and gingerol

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PiperineC₁₇H₁₉NO₃ · black pepper

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6-GingerolC₁₇H₂₆O₄ · ginger

  1. 4Piperine also has an amide and also triggers heat receptors, more mildly. It slows the breakdown of some compounds, which is why it is paired with turmeric to raise curcumin absorption.
  2. 5Gingerol has capsaicin’s head but a ketone and OH in its chain. Drying or cooking ginger turns it into shogaol, which is even more pungent.

What it is: The pungent compounds of black pepper (piperine) and fresh ginger (gingerol).

In your body: Ginger is one of the better-studied food remedies: it modestly relieves nausea, including morning sickness, in several trials. Piperine’s effect on absorption can also raise blood levels of some medicines.

Found in: Black and white pepper; fresh, dried and candied ginger, ginger tea.

carbon hydrogen oxygen nitrogen · every molecule on this page is drawn at the same scale with every hydrogen shown · tap one to enlarge it

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Figure 8

Caffeine and Theobromine

The stimulants of coffee, tea and chocolate.

Alkaloids

Caffeine and theobromine

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CaffeineC₈H₁₀N₄O₂

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TheobromineC₇H₈N₄O₂

  1. 1Caffeine is a purine, related to the A and G of DNA, with three methyl groups.
  2. 2Theobromine, from cocoa, has an N-H here instead of the third methyl. The liver turns some caffeine into theobromine.

What it is: Alkaloids: bitter, nitrogen-containing plant compounds, here made to deter insects. Caffeine is the most widely used stimulant in the world.

In your body: Caffeine blocks adenosine, the brain signal that builds up sleepiness, so you feel more alert; it takes effect in 15–45 minutes and its half-life is about 5 hours in adults. Theobromine is a much milder stimulant. Moderate coffee and tea drinking are linked to lower risk of several diseases.

Too much: The US FDA says up to 400 mg a day is generally not linked to harmful effects in healthy adults; pregnancy guidance is 200 mg a day or less. Too much causes jitters, fast heartbeat, anxiety and poor sleep; concentrated powders can be deadly. Theobromine is toxic to dogs, which clear it slowly, so keep chocolate away from them.

Found in: Coffee, tea, yerba mate, cola and energy drinks, cocoa and chocolate (mostly theobromine, some caffeine), guarana.

How much caffeine
Drink or foodTypical caffeine
Brewed coffee, 8 oz (240 mL)80–100 mg
Espresso, 1 shotabout 60–75 mg
Black tea, 8 ozabout 40–50 mg
Green tea, 8 ozabout 30–50 mg
Cola, 12 oz (355 mL)about 30–40 mg
Energy drink, 8 ozabout 70–100 mg
Dark chocolate, 1 oz (28 g)about 12–25 mg

carbon hydrogen nitrogen oxygen · every molecule on this page is drawn at the same scale with every hydrogen shown · tap one to enlarge it

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Figure 9

Where bioactives are used in the body

Tap a number on the cell to see what that part does; the list below it gives every other place in the body.

Not essential, but active: plant compounds that reach your eyes, gut, blood vessels and brain.

Inside a cell

A typical animal cell, not to scale. Real cells hold thousands of ribosomes and hundreds of mitochondria.

Plant compounds that aren't nutrients still change how cells behave.

  1. Sulforaphane from broccoli turns on Nrf2, which switches on the cell's own antioxidant and detox genes.
  2. Plant sterols and some polyphenols act at the membrane; polyphenol-rich foods are linked to better blood-vessel function.
  3. Many polyphenols are only weak antioxidants directly; their main effect is changing cell signals.
  4. Caffeine and catechins slightly raise fuel burning; resveratrol is studied for mitochondrial effects, mostly in lab cells.
  5. Liver enzymes change most polyphenols so they can be removed; grapefruit compounds block one of these enzymes (CYP3A4), which affects some drugs.
  6. Caffeine blocks adenosine receptors, which is why it keeps you alert.

Everywhere else in the body

Each item, the places outside the cell where it is found or used, and what it does there.

Carotenoids

  • Retina. Lutein and zeaxanthin collect in the macula and filter blue light.
  • Eye lens and brain. Also hold lutein.
  • Skin. Beta-carotene and lycopene tint it slightly.
  • Fat tissue. Stores carotenoids.
  • Liver. Turns beta-carotene into vitamin A.
  • Blood. Carried in lipoproteins.
  • Prostate, adrenal glands and testes. Concentrate lycopene.

Caffeine

  • Brain. Blocks adenosine, the signal that builds up as you get tired.
  • Heart. Can raise heart rate a little.
  • Stomach. Increases acid.
  • Kidneys. Mild extra urine in people not used to it.
  • Liver. Clears it (CYP1A2); its half-life is about 3 to 7 hours.
  • Placenta and breast milk. Pass it to the baby.

Capsaicin

  • Mouth, skin and gut. Opens the heat-pain receptor (TRPV1): the burn of chili.
  • Nerves. Repeated use dulls pain nerves, which is why it is used in pain creams.

Polyphenols (flavonoids and others)

  • Small intestine. Absorbs only a small share.
  • Large intestine. Bacteria break most into smaller molecules, which are absorbed.
  • Liver. Tags them for removal.
  • Blood vessels. Cocoa and tea flavanols can help vessel walls relax.
  • Kidneys. Send the products out in urine.

Phytosterols

  • Small intestine. Block some cholesterol from being absorbed; about 2 grams a day lowers LDL by roughly 6 to 12%.

Glucosinolates and sulforaphane

  • Mouth. Chewing broccoli mixes its enzyme with glucosinolates to make sulforaphane.
  • Large intestine. Bacteria make some when the vegetable is cooked.
  • Liver. Sulforaphane switches on detox and antioxidant enzymes.
  • Bladder. The products concentrate in urine.
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Figure 10

Putting It All Together

The whole lesson in one table, plus a few extras.

The bioactives at a glance
BioactiveFamilyWhat it may doMain sourcesGood to know
Flavonoids (quercetin, anthocyanins)polyphenolssupport blood vessels; linked to lower heart riskonions, berries, apples, tea, cocoacolor tells you: red, purple, blue
Isoflavones (genistein)polyphenolsweak estrogen effectssoy foodssoy foods are considered safe
Resveratrol, chlorogenic acid, hydroxytyrosolpolyphenolsantioxidant; linked with coffee and olive oil benefitsgrapes, coffee, extra-virgin olive oilwine has too little resveratrol to matter
Carotenoids (β-carotene, lycopene, lutein)terpenoidsprovitamin A, antioxidants, eye pigmentsorange, red and dark green producecook with a little fat; smokers avoid β-carotene pills
Phytosterolsterpenoidsblock cholesterol absorptionoils, nuts, fortified spreadsabout 2 g a day lowers LDL 8–10%
Sulforaphane, allicinsulfur compoundsswitch on the body’s own defensesbroccoli, cabbage, garlic, onionschop, wait, do not overboil
Capsaicin, piperine, gingerolpungent compoundstrigger heat receptors; ginger eases nauseachili, pepper, gingerfat, not water, cools chili heat
Caffeine, theobrominealkaloidsblock adenosine; alertnesscoffee, tea, cocoaup to 400 mg caffeine a day for most adults
Worth knowing

Antioxidant claims

Test-tube antioxidant scores do not predict effects in the body, and the USDA withdrew its antioxidant (ORAC) database in 2012 for that reason. Many polyphenols probably work by signaling rather than by mopping up free radicals directly.

Grapefruit and medicines

Grapefruit contains furanocoumarins, bioactives that block an enzyme in the gut that breaks down many drugs, raising their blood levels. Many statins, blood pressure drugs and others carry a grapefruit warning.

Same compound, two sides

Tannins, phytate and glucosinolates appear in Antinutrients too: whether a compound helps or hinders depends on the dose, the rest of the diet and how the food is prepared.

General education, not medical advice. Facts follow mainstream sources (NIH Office of Dietary Supplements and National Center for Complementary and Integrative Health, US FDA, EFSA, Linus Pauling Institute, standard food-science texts).

Quiz

Tap a question to see the answer

1. What makes a compound a bioactive rather than a nutrient?

It acts on the body but is not essential, so there is no deficiency disease (Figure 1).

2. What is a phenol, and what makes a polyphenol?

An OH group on a benzene ring; a polyphenol has several (Figure 2).

3. Why does red cabbage turn blue when cooked with baking soda?

Its anthocyanins change color with acidity: red in acid, blue-green in alkali (Figure 2).

4. Which food is the main source of isoflavones, and how do they act?

Soy; they act like a weak estrogen (Figure 2).

5. Which polyphenol is the main one in coffee?

Chlorogenic acid (Figure 3).

6. What five-carbon unit are carotenoids and sterols built from?

Isoprene (Figure 4).

7. How do beta-carotene and lycopene differ?

Beta-carotene has a ring at each end and is provitamin A; lycopene is an open chain, red, and not made into vitamin A (Figure 4).

8. How do phytosterols lower LDL cholesterol?

They crowd cholesterol out of the bile mixtures that carry it into gut cells, so less is absorbed (Figure 5).

9. What enzyme makes sulforaphane, and when does it act?

Myrosinase, when broccoli is cut or chewed; hard boiling destroys it (Figure 6).

10. Which receptor does capsaicin switch on, and what cools the burn best?

TRPV1, the heat receptor; milk or other fatty foods (Figure 7).

11. How does caffeine make you feel alert?

It blocks adenosine, the brain signal for sleepiness (Figure 8).

12. What daily caffeine amount does the FDA say is generally safe for healthy adults?

Up to 400 mg, about four cups of brewed coffee (Figure 8).

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