Years to your life, life to your years

Ageing is a fickle thing. Consumer hopes traditionally arrived via anti-wrinkle creams. Later came hormones and antioxidants. Tantalising new research is showing that natural bioactives can not only help prevent the early onset of chronic degenerative diseases of ageing, but can also increase lifespan. Todd Runestad assesses the state of the science

The healthy ageing category can be so broad as to be elusive. Retailers routinely organize their supplement shelves by health condition, but you'd be hard pressed to find a category titled Anti-Ageing, let alone Immortality. Hormones are routinely dispensed, such as DHEA (dehydroepiandrosteron), a testosterone precursor similar to andro (short for androstenedione), the one that made former baseball slugger Mark McGwire infamous. Because of the controversy surrounding steroids and their precursors, we will not be addressing or advocating for them here.

There are two paradigms when it comes to the anti-ageing world: adding years to your life, a la Ponce de Leon, and adding life to your years, which means staving off the chronic degenerative diseases of ageing. Natural functional ingredients can address both of these.

Years to your life
Can natural functional ingredients really make you actually live longer? Not just age more gracefully but actually net you years to your life? The evidence is starting to come in, and the answer looks like a yes.

The most recent evidence was a March 2010 study in which researchers gave mice a daily multi-vitamin containing 30 common nutritional ingredients. The formulation was developed to target five key mechanisms of ageing: oxidative stress, inflammation, mitochondrial function, insulin resistance and cell membrane integrity. Of these, the most compelling aspect to researchers was free radicals generated within cellular mitochondria. Supplements that targeted mitochondrial performance included carnitine, coQ10 and fish oils.

Antioxidants were seen as important because accelerated ageing is linked to free radical generation, said the researchers. Antioxidants in the study included vitamins A, C and E, selenium, and N-acetyl cysteine. The free radical theory of ageing as well as the mitochondrial theory of ageing proffer benefits with antioxidants as well as mitochondrial ingredients.

In nonsupplemented mice, the mitochondrial function dropped to 46 per cent of youthful levels at the human equivalent of 75 years old. But the supplemented mice, in contrast, exhibited a "remarkable" 56 per cent gain in mitochondrial activity, and a similarly significant gain in energy.1

The supplemented mice also lived 11 per cent longer.

In addition, the researchers gave the supplement blend to grasshoppers — they lived twice as long!

To watch a televised news report on the research, and to read the published study, go to www.functionalingredients

This research echoes with the breakthrough research on resveratrol in 2006 by researchers at Harvard University whose mice lived 31 per cent longer. Resveratrol is found in red wines (particularly pinot noir varieties) and is produced by a variety of plants when put under stress.

The lead researcher, David Sinclair, PhD, started publishing research using resveratrol in 2003 when he found the red-wine polyphenol turned on the SIRT1 gene, which mimics calorie restriction, a phenomenon that slows the pace of ageing and increases maximum lifespan. Scientists have been able to increase the lifespan of a variety of species by reducing their normal food consumption by 30-40 per cent.

In yeast cells, they lived 70 per cent longer.2

In fruit flies, the Drosophila melanogaster lived more than one-third longer.

In fish, they lived almost 60 per cent longer.3

In mice, middle-aged rodents fed a high-calorie diet with reservatrol approximated mice on a standard diet, compared to those high-calorie mice that did not take resveratrol, which had a 31 per cent higher risk of dying. The resveratrol mice, beyond living longer, also had increased insulin sensitivity, increased mitochondrial number and improved motor function. They lived longer — and better.4

(A later study found resveratrol given to mice starting in mid-life led to a marked reduction in signs of ageing, from decreased inflammation to reduced cataract formation and preserved bone mineral density — but they did not live longer.5)

But vitamin D — that might make you live five years longer. This is according to researchers who discovered the sunshine vitamin can maintain the length of telomeres — the protective, shoelace-tiplike ends of DNA strands that decrease in length with each cell cycle and with increased inflammation. They are seen as a predictor of age-related disease, and they are all the rage, especially since an American team won the 2009 Nobel Prize in medicine for their research on telomeres. Researchers measured serum vitamin D concentrations in 2,160 women aged 18-79 years old from a large population-based cohort of twins. The difference between those with the highest vitamin D levels and the lowest had telomeres that lasted five years longer.6

Inflammation and oxidative stress are key determinants in the biology of ageing, and telomeres are the new marker

"Inflammation and oxidative stress are key determinants in the biology of ageing, and LTL (leukocyte telomere length) dynamics appear to chronicle the accruing burden of these variables," wrote the research team from the UK.

A recent human trial discovered that homocysteine levels can also affect telomere length — but only in older men. Australian researchers did not find any affect in either younger people or in women. This is notable nutritionally because B vitamins, including folic acid, B6 and B12, may help lower blood levels of homocysteine.7

A human study published in the Journal of the American Medical Association in January 2010 found that of 608 patients with stable coronary heart disease, those with the highest levels of omega-3 DHA and EPA had the slowest rate of telomere shortening over a five-year study period.8

Among 586 participants in another human study, multivitamin use was associated with 5.1 per cent longer telomeres. In the analysis of micronutrients, higher intakes of vitamins C and E from foods were each associated with longer telomeres, even after adjustment for multivitamin use. Further, intakes of both nutrients were associated with telomere length among women who did not take multivitamins.9

Telomere lengthening is also finding sway with cosmetics makers, who are touting products that contain natural functional bioactives that claim to maintain telomere length.10

Life to your years
Adding life to your years means staving off the chronic degenerative diseases of ageing. These health conditions provide ripe grounds for new product development because consumers gravitate to supplements and other health products that tout effectiveness against specific health concerns. Four conditions in particular include vision health, bone and joint health, and cognitive health.

Vision: The carotenoids lutein, zeaxanthin and astaxanthin helped boost the overall fortunes of the supplements world in 2008, according to Nutrition Business Journal (NBJ). Vision-health product growth was 48 per cent in 2008 — three times more than the second-place condition, which was bone health, according to NBJ.

Lutein and zeaxanthin are uniquely concentrated in the retina and lens, making them affect those two vital ocular tissues. Most of epidemiological studies and clinical trials support the notion that lutein and zeaxanthin have a potential role in preventing and treating certain eye diseases such as age-related macular degeneration, cataract and retinitis pigmentosa. The biological mechanisms for the protective effects of these carotenoids may include powerful blue-light filtering activities and antioxidant properties.11

The macular pigment is a yellowish orb near the center of the retina in the eye. It absorbs harmful UV and blue light, making it a sort of sunglasses for the eye. It is important because the macula degenerates as people age — the leading cause of blindness in the elderly is macular degeneration. The detrimental effects of glaring light on visual function, including visual discomfort and greatly reduced contrast, are common problems for millions of people. Lutein and zeaxanthin can help reduce the deleterious effects of glare, improve visual performance and help shield against harmful blue light through antioxidant mechanisms.12

An Italian double-blind, placebo-controlled, randomised human trial gave 27 patients with nonadvanced age-related macular degeneration a supplement cocktail that included 180mg vitamin C, 30mg vitamin E, 22.5mg zinc, 1mg copper, 10mg lutein, 1mg zeaxanthin and 4mg astaxanthin daily for 12 months. At both six and 12 months, the supplemented group experienced increased macular thickness and improved vision in the central retina but not in the more peripheral retinal areas.13

Omega-3 fatty acids can also help with vision. In a comparison of twins, those who did not smoke, and those who ate more fish or who consumed more omega-3s, had reduced risk of age-related macular degeneration than their twins who smoked and who ate less fish or consumed less omega-3s.14

Another study found high omega-3 intake could delay macular degeneration.15

Carnitine, coQ10 and omega-3s given to 106 patients of early age-related macular degeneration in a randomised, double-blind, placebo-controlled clinical trial experienced significant improvement in macular markers.16

Green tea catechin EGCG was found to fight glaucoma and other eye diseases. Researchers who fed rats green tea found the lens, retina and other eye tissues absorbed the green tea nutrients. The retina absorbed the highest levels of gallocatechin, while the aqueous humor tended to absorb epigallocatechin. The effects of green tea catechins in reducing harmful oxidative stress in the eye lasted for up to 20 hours. "Results indicate that green tea consumption could benefit the eye against oxidative stress," said the researchers.17

Cognitive: There are many different ways to slice the cognitive-health market — from brain function to memory and mood. It has risen to become the top health concern among the geriatric set, according to Mintel research. B vitamins are important here, in particular choline — a precursor for biosynthesis of the neurotransmitter acetylcholine. Choline is also required to make certain phospholipids — essential components of all cell membranes — in particular phosphatidylcholine.18

In a recent rat study, neuroscience researchers found that choline improved memory, and choline deficiency impaired memory performance.19 This idea was validated in humans in an October 2009 study of 5,918 adults in two Norwegian age groups, 46-49 year olds, and 70-74 year olds. Those with the lowest plasma choline levels had the highest anxiety levels, though researchers found no correlation to choline and depression.20

The omega-3 fatty acids, in particular DHA, also address parameters of cognitive health. Lower blood levels of omega-3s and phospholipids correlated with a greater number of behavioural problems in boys ages 6 to 12, from temper tantrums to sleep problems.21 British researchers gave 41 children ages 8 to 12g omega-3s or placebo for 12 weeks. The fish oil group had significantly less general behaviour and cognitive problems, according to seven of 14 measurement scales. The treatment group also showed fewer ADHD-related symptoms.22

Phosphatidylserine (PS) helps comprise cell membranes and is especially concentrated in the brain — hence its utility in a range of cognitive concerns from ADHD to Alzheimer's and depression.23,24 And because omega-3 fatty acids also accumulate in the brain, researchers combined PS with EPA and DHA in a three-month, randomised, double-blind study of 60 children with ADHD. With PS acting as a carrier to more effectively ferry the omega-3s into the brain, those children taking the PS combination scored higher on the visual sustained attention performance scale than the omega-3 group.25

Moving along the age scale, new mothers with the lowest plasma levels of omega-3s experienced the highest incidence of post-partum depression — the 'baby blues,' which conservatively can affect 16 per cent of women. Numerous studies, including randomised, controlled trials, have found an association between low omega-3 levels and a higher incidence of maternal depression. Short of depression, maternal mood can be altered with low levels of omega-3s, as well as vitamin B12, folic acid, calcium, iron, selenium and zinc.26

A recent meta-analysis of 10 double-blind, placebo-controlled human clinical trials found a positive antidepressent effect of omega-3s.27 One psychiatrist recommends between 700 and 1,500mg/day DHA to prevent major depression, based on her assessment of the literature.28

Consuming 180mg/day DHA, or 2.7 servings of fish a week, was associated with a 50 per cent reduction in dementia, according to an assessment of 5,209 adults in the Framingham Heart Study.29

Bone: Bone health continues to be a strong growth category, driven by the explosion of vitamin D sales. This category grew 16 per cent to $1.4 billion in sales in 2008, according to NBJ. The US Food and Drug Administration recently amended the health claim for bones, adding D to calcium's efficacy in maintaining healthy bone mineral density. And with the US Institute of Medicine poised to revise its recommended daily value for vitamin D to 1,000IU and potentially 2,000IU a day (up from 400IU), vitamin D's fortunes will continue to grow. Already in April 2010, Finland doubled its vitamin D recommendation to 800IU/day.

Bone-health supplement formulas generally have a baseline of ingredients — calcium, vitamin D and magnesium. Vitamin D has long been recognised to be necessary for efficient calcium absorption. For the postmenopausal set, calcium and vitamin D together have been shown to prevent bone loss and decrease bone breaks. And magnesium is typically formulated at a 1:2 ratio to calcium.

"The hidden cause of calcium deficiency is the fact that available calcium is not being assimilated by the body due to a lack of magnesium," says Ken Whitman, vice president of marketing at Burbank, California-based Peter Gillham's Natural Vitality. "Without a proper balance of these two minerals, magnesium gets depleted, which will result in the negative effects associated with lack of magnesium and a build-up of unassimilated calcium."

Inulin is increasingly being used to boost calcium absorption, in adolescents, young adults and older women.30 Studies show 8g/day inulin can boost calcium absorption. One study gave adolescents 8g/day inulin-type fructan prebiotics for one year. Those taking the prebiotic experienced significantly increased calcium absorption and enhanced bone mineralization during pubertal growth.31

Vitamin K2 is beginning to amass enough research to make it a player in the bone-health market. Vitamin K activates osteocalcin in bones, which binds calcium to the surface of bones. The longer-chain menaquinones, MK-4 and MK-7, are commercially available.

One important placebo-controlled intervention study on 155 postmenopausal women gave groups either a supplement containing calcium, magnesium, zinc and vitamin D; the same combination plus vitamin K1; or placebo, for three years. At the end of the study, researchers measured any changes in bone mineral density. The difference between the K1 group and placebo was 1.7 per cent, and 1.3 per cent between the K1 group and the other supplementing group.32

A population-based study in Japan looked at women in eastern Japan (Tokyo), where menaquinone-7-rich natto is routinely eaten, and western Japan (Hiroshima), where natto is not generally consumed. Researchers found a statistically significant inverse correlation between incidence of hip fractures in women and natto consumption.33

A head-to-head comparison study between vitamin K1 and menaquinone-7 vitamin K2 found both were absorbed well, with peak serum concentrations at four hours after intake. However, the half-life of vitamin K2 was seven to eight times as long as vitamin K1, which resulted in a more complete carboxylation of osteocalcin.34

Even green tea has now been found to help with bone health. The green tea catechin epigallocatechin (EGC) boosted the activity of a key enzyme that promotes bone growth, by up to 79 per cent. EGC also significantly boosted levels of bone mineralization in the cells, which strengthens bones. The researchers also showed that high concentrations of ECG blocked the activity of a type of cell that breaks down or weakens bones.35

Joints: Products aimed specifically at joint health have grown over the past four years from $1.26 billion to $1.56 billion, but the growth rate per year declined to only 2.2 per cent in 2008, according to NBJ. This might suggest a near-saturation of the market, but there are enough new ingredients coming into the market to give manufacturers options in reformulating and gaining market share.

Glucosamine and chondroitin are the well-known one-two punch leaders in the category. Just to confirm their bona fides: randomised, double-blind, placebo-controlled human clinical trials show that 1,500mg/day glucosamine has reduced knee pain in a three-year study, and 1,200mg/day chondroitin has reduced knee pain in a four-month study.36,37

New entrants to the category can boast either working via different mechanisms, thereby making them suitable formulation partners, or in some cases these functional ingredients are being shown to work even more effectively than glucosamine and chondroitin.

A case in point is undenatured type II collagen. A recent human clinical trial compared UC-II brand collagen with a combination of glucosamine and chondroitin in treating osteoarthritis of the knee. Collagen contains a matrix of glycosaminoglycans including hyaluronic acid. After 90 days, UC-II reduced the WOMAC osteoarthritis index score by 33 per cent, compared to 14 per cent in the glucosamine/chondroitin group. In the visual analog scale score, the results were similar: 40 per cent decrease in the UC-II group, compared to 15.4 per cent in the glucosamine/chondroitin group. Pain scores showed a 20 per cent decline in the UC-II group compared to a six per cent decline in the glucosamine/chondroitin group.38

Fast-acting is the story here, though, because while glucosamine and chondroitin are effective, it can take up to six weeks for effects to be noticed. To that end, another new entrant to the category is natural eggshell membrane (NEM). In a randomised, multicenter, double-blind, placebo-controlled study for eight weeks on 67 patients, 500mg NEM led to a significant improvement in pain (15.9 per cent reduction) and stiffness (12.8 per cent decline) after 10 days of supplementation. While there was a trend for overall WOMAC score decline, it did not reach significance after 60 days.39

Another new entrant is boswellia, known traditionally as frankincense. 5-Loxin, a proprietary frankincense extract, was shown to improve pain and physical function scores after seven days in 75 osteoarthritis patients.40

And one of the hotter ingredients on the market today is krill, which has the omega-3s DHA and EPA as well as phospholipids, astaxanthin, protein and other antioxidants. There has been only a handful of published human clinicals on krill, but one of them was to measure krill's effects on chronic inflammation in patients with osteoarthritis. After seven days, the Neptune Krill Oil brand krill reduced C-reactive protein levels (a marker of inflammation) by 19.3 per cent, compared to an increase of 15.7 per cent in the placebo group. After 14 and 30 days of treatment with 300mg krill, the krill group experienced further C-reactive protein declines of about 30 per cent, while the placebo group experienced further increases, of 32 per cent after 14 days and 25 per cent after 30 days.41

Functional-food and beverage use by age group

All age groups:


18-24 years old:


25-34 years old:


35-44 years old:


45-54 years old:


55-64 years old:




Source: Mintel


Trends by the dozen

  1. Seniors eat very differently from other age groups. They are not your functional food buyers, at least not up to this point.
  2. Why aren't they buying functional foods? Seventy per cent of those older than 65 say foods and beverages should be tested by the FDA or a government agency for health claims.
  3. No one has come up with an answer for vitality and energy. It's a hole in the market. Energy drinks are really for 18-24 year olds. Older people are just as weary but are not buying energy drinks. What do they like? Supplements.
  4. In foods, there are other ways to talk about digestion: low-acid coffee, tomato sauce or orange juice. The whole category has a tremendous amount of legs as these 100 million people age.
  5. Probiotics are a very lucrative category. I just don't know, from looking at yoghurt, that food is the way to deal with probiotics in this age group.The form that's most appealing is still up for discussion.
  6. Best-selling products for the older set say "clinical strength" or "expanded effectiveness" or "doctor recommended." Older people are very in tune with their doctors.
  7. They have the No. 1 sweet tooths by a country mile.
  8. In the 50+ age group, there's been a major shift in the last two years. Now it's retaining mental sharpness followed by heart disease and cancer, with eye health up sharply.
  9. Menopause lasts about four years. It's the biggest supplements void out there.
  10. Omega-3s are hot; seniors take twice as much as anyone, as well as calcium. Vitamin D sells well among all groups.
  11. How many falls among older women are not from weakness of bone but actually weakness of muscle? The top issue in the next 10 years is sarcopenia — protein, amino acids, lysine, cysteine, vitamin D, calcium, CLA, creatine all work with staying physically strong.
  12. Boomers are No. 1 for topical medications. We should take this whole area of joint pain to a whole new level.


The skinny on lutein
The traditional way to view healthy ageing was less than skin deep: you looked younger if you had fewer wrinkles. While the healthy-ageing conceit has moved on from there, the look of your skin still counts for something.

Lutein, like other carotenoids, has long been used for its vision benefits. It does this as an antioxidant that scavenges light-induced free radicals, and also because it acts as a filter of high-energy blue light — think sunlight.1 Think sun protection. But little has been known about these carotenoids in human skin until recently.

The skin's antioxidant capacity is its first line of defence against UV light. Harvard researchers measuring the efficacy of lutein as well as its carotenoid cousin zeaxanthin found they decrease acute inflammation and lesions after UV-light exposure in mice.2

Researchers in Italy jumped on this research and found a combination of oral and topical lutein and zeaxanthin had the best results in hydrating and protecting the skin following UV-light irradiation; oral was actually superior to topical application.3

Research like this validates the burgeoning 'beauty from within' oral-cosmetic movement. Want to get up on new science, formulation, and business and marketing trends — not to mention interaction and inspiration? Check out the NutriCosmetic Summit, June 10 in Las Vegas, concurrent with the Natural Marketplace 2010 show.

1. Alves-Rodrigues A, Shao A. The science behind lutein. Toxicol Lett 2004 Apr 15;150(1):57-83.
2. Gonzalez S, et al. Dietary lutein/zeaxanthin decreases ultraviolet B-induced epidermal hyperproliferation and acute inflammation in hairless mice. J Invest Dermatol 2003 Aug;121(2):399-405.
3. Palombo P, et al. Beneficial long-term effects of combined oral/topical antioxidant treatment with the carotenoids lutein and zeaxanthin on human skin: a double-blind, placebo-controlled study. Skin Pharmacol Physiol. 2007;20(4):199-210.


Antioxidants age gracefully
FI talks with Lester Packer, PhD, the world's foremost antioxidant research scientist, having published more than 700 scientific papers and 70 books on antioxidants. He is currently at the University of Southern California School of Pharmacy's department of molecular pharmacology and toxicology.

FI: You've done a lot of cellular studies with vitamin E showing it increases the lifespan of cells. Can antioxidants extend human life?

LP: It has not been shown for human life. For animal life, there's an S-shaped curve for length of life of species survival, and that S-shaped curve gets shifted to the right, but the end point doesn't really change. So what has been shown with animal experiments is that the mean life span may be slightly extended, which means you add life to your years, but you don't necessarily add years to your life.

FI: How do antioxidants work with genes in a preventive manner as opposed to where someone already has a condition?

LP: Antioxidants work wherever there is free radical-mediated processes going on. In some cases the fre- radical or oxidative processes might initiate a disease. In other cases there may be multiple stages where antioxidants could be beneficial. Chronic degenerative diseases are of that nature. We're beginning to see in all of these cases that you can slow them.

FI: For example?

LP: Cataracts is a good example. Everybody is going to get cataracts if they live long enough. By the time an American is 85, almost half the population is going to need medical attention for cataracts. Yet there are 10 or 15 studies with different antioxidants showing that you can slow cataractogenesis. This can save billions of dollars that way. I think that's compelling evidence.


Select suppliers: anti-ageing ingredients address a range of conditions

AGN Nutrition
Major vitamin D supplier in technology, formulation and application for human, pharmaceutical and animal feed markets.

Amax Nutrasource
Full-line supplier of resveratrol, chondroitin, glucosamine, MSM, green tea and more.

BioCell Technology
BioCell Collagen II is a natural hydrolyzed type II collagen that supports joint and skin health.

Blue California
Biolut brand lutein micro-encapsulated for supplments; VitaDHA, a nano-encapsulated ingredient derived from fish; 95 per cent EGCG green tea extract, for use in foods, beverages; chicken collagen type II for joints.

Chemi Nutra
SerinAid PhosphatidylSerine and AlphaSoize brand alpha-GPC support cognitive function.

"Beauty from within" line includes Xangold lutein esters, Omevital omega-3s, Covitol natural vitamin E, Vetatene mixed carotenoids and Plantalin green tea.

EZEyes zeaxanthin is available in a 5% beadlet form for capsules, tablets and softgels.

BioAstin natural astaxanthin is produced with microalgae in the Big Island of Hawaii.

Cyvex Nutrition
BioVin Advanced French red wine extract contains 5% resveratrol.

Denomega Nutritional Oils
Omega-3 supplier for food, beverage, supplements, medical foods and pet/animal nutrition.

DNP International
Importer and supplier of more than 1,000 ingredients, including chicken collagen type II, with facilities in New Jersey, Chicago, LA and Shanghai.

FloraGLO lutein for vision health and to capitalize on the market opportunity for lutein's skin-care applications. Optisharp brand zeaxanthin rounds out the carotenoid combo.

Highly concentrated marine-based omega-3 oils with varying ratios of EPA and DHA targeted to different health conditions.

ESM Technologies
NEM patented natural eggshell membrane for joints; ESC eggshell calcium for bones.

Custom fortification prototypes in beverages, bars and more provide targeted turn-key solutions for bone and joint health.

Dermaval is formulated for supplements to improve skin tone and texture.

UC-II undenatured type II collagen is more than twice as effective as glucosamine and chondroitin, at a dose of just 40mg per pill.

Martek Biosciences
life'sDHA is derived from algae via fermentation.

Ocean Nutrition Canada
meg-3 brand fish oils come with Powder-loc double-hulled protection for food and beverage applications.

Pacific Rainbow
Chondroitin sulfate comes derived from bovine, porcine, shark or chicken at 90% minimum. Resveratrol is sourced from giant knotweed at 25% or 50% minimum purity. Hyaluronic acid 1% solution has cosmetics applications.

PL Thomas
5-Loxin is the branded boswellia extract, MenaQ7 is the branded vitamin K2 ingredient.

Curcumin C3 Complex is patented for composition ratio and use as antioxidant, anti-inflammatory and for cognitive issues. Saberry amla extract has cosmetic and nutricosmetic applications.

TandemRain Innovations
AvtivMSM is manufactured exclusively for TandemRain.

TSI Health Sciences
Chondroitin sulfates and glucosamine salts from a range of sources are produced in GMP facilities.


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