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 mag.com/go/mice.
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 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
1. Aksenov V, et al. Dietary amelioration of locomotor, neurotransmitter and mitochondrial aging. Exper Biol Med 2010:235:66-76.
2. Howitz KT, et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 2003 Sep 11;425(6954):191-6.
3. Wood JG, et al. Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 2004 Aug 5;430(7000):686-9. Epub 2004 Jul 14.
4. Baur JA, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006 Nov 16;444(7117):337-42.
5. Pearson KJ, et al. Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab 2008 Aug;8(2):157-68.
6. Richards JB, et al. Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women. Am J Clin Nutr 2007 Nov;86(5):1420-5.
7. The Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006 Apr 13;354(15):1567-77.
8. Farzaneh-Far R, et al. Association of marine omega-3 fatty acid levels with telomeric aging in patients with coronary heart disease. JAMA 2010 Jan;303(3):250-7.
9. Xu Q, et al. Multivitamin use and telomere length in women. Am J Clin Nutr 2009 Mar 11;89:1857-63.
11. Ma L, Lin XM. Effects of lutein and zeaxanthin on aspects of eye health. J Sci Food Agric 2010 Jan 15;90(1):2-12.
12. Nakajima Y, et al. Astaxanthin, a dietary carotenoid, protects retinal cells against oxidative stress in-vitro and in mice in-vivo. Pharm Pharmacol 2008 Oct;60(1):1365-74.
13. Parisi V, et al. Carotenoids and antioxidants in age-related maculopathy italian study: multifocal electroretinogram modifications after 1 year. Ophthalmology 2008 Feb;115(2):324-333.\]
14. Seddon JM, et al. Cigarette smoking, fish consumption, omega-3 fatty acid intake, and associations with age-related macular degeneration: the US Twin Study of Age-Related Macular Degeneration. Arch Ophthalmol 2006 Jul;124(7):995-1001.
15. Johnson EJ, Schaefer EJ. Potential role of dietary n-3 fatty acids in the prevention of dementia and macular degeneration. Am J Clin Nutr 2006 Jun;83(6 Suppl):1494S-1498S.
16. Feher J, et al. Improvement of visual functions and fundus alterations in early age-related macular degeneration treated with a combination of acetyl-L-carnitine, n-3 fatty acids, and coenzyme Q10. Ophthalmologica 2005 May-Jun;219(3):154-66.
17. Chu KO, et al. Green tea catechins and their oxidative protection in the rat eye. J Agric Food Chem 2010 Feb 10;58(3):1523-34.
18. Zeisel SH. Choline: an important nutrient in brain development, liver function and carcinogenesis. J Am Coll Nutr 1992;11(5):473-81.
19. Wong-Goodrich SJ, et al. Spatial memory and hippocampal plasticity are differentially sensitive to the availability of choline in adulthood as a function of choline supply in utero. Brain Res 2008 Oct 27;1237:153-66.
20. Bjelland I, et al. Choline in anxiety and depression: the Hordaland Health Study. Am J Clin Nutr 2009 Oct;90(4):1056-60.
21. Stevens LJ, et al. Omega-3 fatty acids in boys with behavior, learning, and health problems. Physiol Behav 1996 Apr-May;59(4-5):915-20.
22. Richardson AJ, Puri BK. A randomized double-blind, placebo-controlled study of the effects of supplementation with highly unsaturated fatty acids on ADHD-related symptoms in children with specific learning difficulties. Prog Neuropsychopharmacol Biol Psychiatry 2002 Feb;26(2):233-9.
23. Crook T, et al. Effects of phosphatidylserine in Alzheimer’s disease. Psychopharmacol Bull 1992;28:61-6.
24. Maggioni M, et al. Effects of phosphatidylserine therapy in geriatric patients with depressive disoerders. Acta Pasychiatr Scand (Denmark) 1990;81:265-70.
25. Vaisman N, Kaysar N, Zaruk-Adasha Y, Pelled D, Brichon G, Zwingelstein G, Bodennec J. Correlation between changes in blood fatty acid composition and visual sustained attention performance in children with inattention: effect of dietary n-3 fatty acids containing phospholipids. Am J Clin Nutr 2008 May;87(5):1170-80.
26. Leung BM, Kaplan BJ. Perinatal depression: prevalence, risks, and the nutrition link – a review of the literature. J Am Diet Assoc 2009 Sep;109(9):1566-75.
27. Lin PY, Su KP. A meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of omega-3 fatty acids. J Clin Psychiatry 2007 Jul;68(7):1056-61.
28. McNamara RK. Evaluation of docosahexaenoic acid deficiency as a preventable risk factor for recurrent affective disorders: current status, future directions, and dietary recommendations. Prostaglandins Leukot Essent Fatty Acids 2009 Aug-Sep;81(2-3):223-31.
29. Johnson EJ, Schaefer EJ. Potential role of dietary n-3 fatty acids in the prevention of dementia and macular degeneration. Am J Clin Nutr 2006 Jun;83(6 Suppl):1494S-1498S.
30. Coxam V. Current data with inulin-type fructans and calcium, targeting bone health in adults. J Nutr 2008 Nov;137(11 Suppl):2527S-2533S.
31. Abrams SA, et al. A combination of prebiotic short- and long-chain inulin-type fructans enhances calcium absorption and bone mineralization in young adolescents. Am J Clin Nutr 2005 Aug;82(2):471-6.
32. Braam LA, et al. Vitamin K1 supplementation retards bone loss in postmenopausal women between 50 and 60 years of age. Calcif Tissue Int 2003 Jul;73(1):21-6.
33. Kaneki M, et al. Japanese fermented soybean food as the major determinant of the large geographic difference in circulating levels of vitamin K2: possible implications for hip-fracture risk. Nutrition 2001 Apr;17(4):315-21.
34. Schurgers LJ, et al. Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood 2007 Apr 15;109(8):3279-83.
35. Ko CH, et al. Effects of tea catechins, epigallocatechin, gallocatechin, and gallocatechin gallate, on bone metabolism. J Agric Food Chem 2009;57(16):7293-7.
36. Reginster JY, et al. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet 2001 Jan 27;357(9252):251-6.
37. Leffler CT, et al. Glucosamine, chondroitin, and manganese ascorbate for degenerative joint disease of the knee or low back: a randomized, double-blind, placebo-controlled pilot study. Mil Med 1999 Feb;164(2):85-91.
38. Crowley DC, et al. Safety and efficacy of undenatured type II collagen in the treatment of osteoarthritis of the knee: a clinical trial. Int J Med Sci 2009 Oct;6(1):312-21.
39. Ruff KJ, et al. Eggshell membrane in the treatment of pain and stiffness from osteoarthritis of the knee: a randomized, multicenter, double-blind, placebo-controlled clinical study. Clin Rheumatol. 2009 Aug;28(8):907-14.
40. Sengupta K, et al. A double blind, randomized, placebo controlled study of the efficacy and safety of 5-Loxin for treatment of osteoarthritis of the knee. Arthritis Res Ther 2008;10(4):R85.
41. Deutsch L. Evaluation of the effect of Neptune Krill Oil on chronic inflammation and arthritic symptoms. J Am Coll Nutr 2007 Feb;26(1):39-48.