When I'm 64 what will you feed me?

Getting old is annoying. Getting old and ill is really annoying, but it is bad enough to be old and healthy, yet still find oneself a step slower, a little less able to bend over to pick up that stray sock. Can dietary supplements and functional foods have an impact on quality of life while you are still alive to enjoy it? David A Mark, PhD, investigates

Joints. Muscles. Bones. Brain. The great age-related, degenerative downward decline occurs roughly in that order. Cold weather first creeps into ageing joints, hinting that a retirement in warmer climes might be in order. The body sheds muscle mass. Joints hurt before bones break. Finally, cognitive function goes and then it's all over.

Fortunately, recent research — especially in 2008 — is suggesting that warmer, sunnier climes are preferred by the geriatric set for a good reason: vitamin D. The sunshine vitamin really does seem to help whatever ails you.

The current Daily Recommended Intake (DRI) for vitamin D includes an Adequate Intake (AI) of 200IU/day through age 50, 400IU for ages 51-70 and 600IU for those older than 70 years. The current Daily Value is set at 400IU. The Tolerable Upper Intake Level (UL) for adults older than 18 years is currently set at 2,000IU/day. Intake from food is roughly 100-150IU/day; for the one in four adults taking a vitamin D-containing multi or other supplement, that contribution is typically 400IU/day.1

Expect all this to change. There is a growing consensus that serum concentrations in adults are below what is needed to optimise health. Justification for an upward revision was reviewed in early 2009.2

The US Agency for Healthcare Research and Quality (AHRQ) issued a comprehensive report, "Relationships of Vitamin D and Calcium to Nutrient Status Indicators and Health Outcomes," in July 2009. In May 2010, the Institute of Medicine is expected to release revised DRIs for vitamin D and calcium. A reasonably conservative guess would see the AI and UL raised to 1,000 and 5,000IU/day, respectively, for the general adult population.

Two reviews define a serum vitamin D in excess of 75nmol/L as desirable, and estimated a need in excess of 1,000IU/day to move the majority of Americans to this range.3,4 Two other reviews made a convincing case for absence of toxicity in trials as high as 10,000IU/day.5,6 Any ongoing trials of higher amounts of vitamin D should measure serum calcium and kidney function, as these were the bellwethers of setting the existing UL. Many vitamin and mineral companies have leapt ahead of the DRI update to provide products delivering 1,000, 2,000 and even 5,000IU/day — the last more than twice the current UL.

Why does vitamin D matter?
Because people fall down. Specifically, about one third of people over the age of 65 years fall down each year, with one in five requiring medical attention and one in 10 breaking a bone. It happens to younger people, too (Hillary Clinton's elbow). Falls are responsible for the deaths of more than 20,000 people in the US each year — more than murders. Close to 40 per cent of those fatal falls are by people older than 85 years old.7 It is increasingly clear that vitamin D reduces the risk of falls. In postmenopausal women the incidence of falls in one major study was reduced by more than 20 per cent.8

One means by which vitamin D affects risk of falling is by helping maintain physical performance. A three-year evaluation of 979 adults older than 65 years connected serum vitamin D below 20ng/ml with poorer physical performance at the onset of the trial and a greater decline over the subsequent years.9 Evaluation of 242 postmenopausal women showed serum vitamin D correlated to lean body mass, handgrip strength and balance.10 By counteracting muscle-protein catabolism of age-relate sarcopenia, vitamin D may help maintain healthy, functional muscles.11

The contribution of vitamin D to bone health in the aged is a given.12,13 Effects on mental state are not as clear. Alzheimer's disease patients with low levels of serum vitamin D score lower on mental state examinations compared to patients with adequate vitamin D.14 But intervention studies are lacking. As with mental state, research on any effects of vitamin D on osteoarthritis is also in the early stages. Population tracking studies have reported contradictory results (either more joint cartilage loss with low vitamin D, or no effect).15,16

By age 60, four in 10 men and half of all women report that they have joint pain in one or more joints. For the US population as a whole, 50 million have arthritis — half of that osteoarthritis. Osteoarthritis increases with obesity, so prevalence will only worsen over time.

Glucosamine and chondroitin, separately, continue to accrue positive evidence. In a glucosamine follow-up, five years after patients had ended a three-year glucosamine sulphate trial, total knee-replacement surgery had occurred more in the placebo group (14.5 per cent) than in the treated group (6.3 per cent).17 In the STOPP trial, which cites similar long-duration trial results, knee-cartilage loss was only 23 per cent of placebo after two years of chondroitin sulphate at 800mg/day.18

Multiple trial support for Boswellia serrata extracts has been ably summarised.19 A 2008 review of human clinical trials included five that were placebo controlled, and two more with active controls. Three studies were said to be of good methodological quality. The included trials related to asthma, rheumatoid arthritis, Crohn's disease, osteoarthritis and collagenous colitis. Results of all trials indicated that B. serrata extracts were clinically effective. No serious safety issues were noted. The author concluded B. serrata effectiveness is "encouraging, but not compelling."

Hydrolysed collagen, an old stand-by, got new support in a 2009 human clinical trial of 250 Spanish subjects with osteoarthritis of the knee.20 After receiving 10g/day hydrolysed collagen for six months, subjects experienced a significant improvement in knee-joint comfort, as assessed by visual analogue scales to assess pain, and the WOMAC pain subscale. Subjects with the greatest joint deterioration, and with the least intake of meat protein in their habitual diets (collagen is found particularly in meat), benefited most.

Eggshell membrane made the scene with two 2009 studies.21 In one randomized, multi-centre, double-blind, placebo-controlled clinical trial, 67 patients with osteoarthritis taking 500mg/day for eight weeks experienced a statistically significant improvement in rate of response (up to 26.6 per cent compared to placebo) for both pain and stiffness, and trending toward improvement for function and overall WOMAC scores. The natural eggshell membrane was well tolerated. In a pair of open-label clinicals with 39 patients, 500mg/day significantly reduced pain, both at seven and 30 days.

In contrast, support for MSM has stalled even after the 2006 publication of a modestly beneficial trial at 6,000mg/day.

Sarcopenia is a word derived from the Greek 'flesh, loss of,' or more poetically, 'poverty of the flesh.' The term is absolutely modern compared to osteoporosis and osteoarthritis, in that it was not coined until 1988.22 In nursing-home parlance, clients have 'the dwindles' when a pattern of progressive weight loss and decreased quality of life are seen without apparent cause. As noted above, athletic performance even in fit and motivated athletes starts declining faster and faster after age 60. Exercise is the best method to slow, stop and even partially reverse muscle loss.

Does protein-intake quantity matter? The dogma according to the DRIs for protein is that it does not. The Estimated Average Requirement and Recommended Dietary Allowance are 0.66 and 0.80g/kg body weight/day, respectively, across the board, ages 19 years and up. This corresponds to about 55g/day for a 150-pound person. There are mixed opinions as to whether increasing protein intake above the RDA, either by itself or in combination with exercise, could have an anabolic effect on lean body mass. There are claims that protein is directly anabolic and also increases insulinlike growth factor. But as kidney function declines with age, some care must be taken not to overburden kidneys with the task of disposing of excess nitrogen from protein. (For more on protein and muscle effects, see "Formulations," in this issue.)

Bone is continually being remodeled by the constructive actions of osteoblasts and the destructive actions of osteoclasts. Hips, spine and wrists contain trabecular bone, which is remodeled on the order of 20 per cent each year compared to four per cent for cortical bone. Trabecular bones are the ones that weaken and break in osteoporosis. Peak bone density is reached at age 35. By age 80, women will have half the calcium in their bones that they did at half that age. Multiple meta-analyses confirm that calcium supplementation, vitamin D supplementation and the combination of the two each increase bone density (as does exercise). A 2005 study published in JAMA reported that vitamin D at 700-800IU/day combined with 1,200mg/day calcium resulted in a 25 per cent reduction in fractures.8

A 2007 randomised, placebo-controlled, clinical intervention study among 325 postmenopausal women receiving 45mcg/day vitamin K2 for three years found that hip-bone strength remained unchanged, whereas in the placebo group bone strength decreased significantly.23

Less convincing, but interesting, is evidence from epidemiological studies that higher intakes of vitamins E, K and B12, and minerals magnesium, copper, manganese and boron are associated with higher bone density. Dietary shortfalls of one or more of these nutrients are common in adults, especially the elderly. Some dietary supplements intended to help maintain healthy bones combine several of these nutrients with calcium and vitamin D.

The updated cliché is that normal ageing is when you forget where you left your cell phone, whereas dementia is when you no longer know how to use the apps.

The declines in cognitive function start much later than the bone-, joint- and muscle-hardware problems. Chess and bridge players stay competitive into their 70s. Dementia (Alzheimer's and/or vascular) affects about five per cent of people ages 70-80, 24 per cent for 80-90 and more than 40 per cent for people older than 90 years old; it is the seventh leading cause of death in the United States.7

Fish oil, or more specifically docosahexanoic acid (DHA), continues to gain support as protective against dementia.24,25 Fish oil has the bonus benefit of reducing the risk of depression and rheumatoid arthritis (but not osteoarthritis).26

The evidence to date for flavonoid-rich foods such as blueberries, cocoa or red wine is either animal or epidemiological. An Italian survey of 15,807 elderly people detected cognitive impairment in 19 per cent of alcohol drinkers and 29 per cent of nondrinkers. The benefit remained after correcting for other known risk factors.27 Evidence for vitamin D is too preliminary to make a recommendation.28 This also is true for resveratrol, for which there are no human efficacy trials in the scientific literature yet for any indication.

Successful ageing is a choice. In this country, a person who makes it to 50 years has an average life expectancy of another 31 years. Surely 50 is a good time to start paying attention to a healthy lifestyle. Somewhere around 64 may be the last best chance to make a significant difference. Gaining a few extra years of life at the end is a bonus, but the real payoff is a much higher quality of life for the majority of remaining years. Exercise improves quality of life and lifespan. Unless a downside risk appears during the ongoing vitamin D reviews, expect the adult AI to be revised to at least 1,000IU/day, and possibly 2,000IU/day. As this target cannot realistically be met by today's diet, one consequence should be a wider array of approved fortified foods.

Supplements and functional foods targeting vascular health should be able to help people maintain the capacity for exercise with the added bonus of helping with normal blood pressure. Evidence continues to accrue for glucosamine and chondroitin, separately, for joint health. More protein and better-quality protein may contribute to retaining lean body mass with age. DHA from fish oil or algae extraction will benefit vascular health and brain function, as will flavonoids from cocoa, grapes and perhaps other sources.

David A Mark, PhD, is president of dmark consulting, a Boston-area science consulting firm. His 25 years of industry R&D experience includes functional foods, dietary supplements and medical-nutrition products. www.dmarknutrition.com

Disclosure: Mark has as clients dietary-supplements companies that market products targeting bone, joint, muscle and brain health.

Exercise, exercise, exercise
A regular habit of moderate to vigorous exercise four or more days a week outperforms any food or supplement vis-à-vis preserving muscle mass, bone strength, joint health, balance, co-ordination and reflex time. Results accrue to not just quality of life but to lifespan as well.

As such, acknowledging the contributions of exercise in the marketing of any functional food or dietary supplement only adds credibility to the product's overall message. Furthermore, positioning foods and supplements as helping achieve an active lifestyle can tie these products to strongly proven benefits of maintaining physical (and mental) fitness. This global approach to 'performance nutrition' has vast growth potential.

Exercise research also gives a portrait of healthy ageing — and identifies possible targets for intervention. Peak athletic performance is achieved around ages 30&-35, followed by a gradual linear decline through ages 55-60, and then a steeper, nonlinear decline beyond 60 years. Surprisingly, even male professional golf players peak at around age 35. Research with endurance athletes identifies an age-related decline in maximal oxygen consumption (VO2 max), while at the same time there is no change in the metabolic (calorie) cost of performing exercise.1 That decrease in VO2 max occurs through a combination of age-linked decline in maximum heart rate, smaller blood output per heart beat as well as less oxygen extraction as blood courses through muscles. In theory, improved arterial-wall flexibility could help with the last two. In aged animal models, foods (blueberries, Concord-grape juice) known to improve arterial flexibility reversed age-associated declines in strength, co-ordination, balance and memory.2


1. Tanaka H, Seals DR. Endurance exercise performance in Masters athletes: age-associated changes and underlying physiological mechanisms. J Physiol 2008;586:55-63.
2.Shukitt-Hale B, et al. Effects of Concord grape juice on cognitive and motor deficits in aging. Nutrition 2006;22:295-302.

Select suppliers: New-age ingredients for age-old ageing

AHD International
For bones (and cardiovascular health), Vitamin K2 MK7 is available in 1,000ppm and 2,500ppm, with a shelf life of 18 months.

Aker BioMarine
For joints and cognitive, Superba krill oil has omega-3s, as well as phospholipids.

For joints, Antarctic krill with 42 per cent phospholipids, omega-3s and antioxidants.

Bergstrom Nutrition
For joints, OptiMSM is the only current brand of MSM supported by US clinical research in peer-reviewed journals.

Bio Serae
For joints, Osteol milk-protein fraction improves chondrocyte protection under inflammatory stress conditions, hence reducing pain.

BioCell Technology
For joints, BioCell Collagen II is a naturally occurring and bioavailable complex of hydrolysed collagen type II, hyaluronic acid and chondroiting sulfate.

Chemi Nutra
For cognitive health, SerinAid PhosphatidylSerine has two FDA health claims for cognitive dysfunction and dementia in the elderly.

For cognitive, BioVinca periwinkle extract with 98 per cent vincamine acts as a cerebral vasodilator.

For cognitive health, Sharp*PS is an exclusive conjugated phosphatidylserine-omega-3 compound that emulates human brain PS and is the compound used in many clinical studies.

For joints, EPAX 4510 TK is a formula based on clinical trials with high levels of concentrated EPA.

ESM Technologies
For joints, NEM is a food-form matrix of naturally occurring hyaluronic acid, chondroitin and collagen. For bones, ESC eggshell calcium builds bone density.

InterHealth USA

For joints, UC-IIUC-II is undenatured native type 2 collagen.

Kyowa Hakko
For cognitive health, Cognizin citicoline is shown to increase concentration and focus.

For cognitive, as well as heart and eye health, life'sDHA is vegetarian, fermented omega-3 DHA.

Ocean Nutrition Canada
For cognitive health, joints and more, Meg-3 brand omega-3 EPA/DHA from fish oil.

OVOS Natural Health
For cognitive, Vivimind is a patented, science-based natural ingredient based on homotaurine, found in certain seaweed.

Pharmachem Labs
For joints, Celadrin can be used topically or taken as a tablet, capsule or softgel.

PL Thomas
MenaQ-7 brand vitamin K2 for bone and cardiovascular health.

Proprietary Nutritionals
Perluxan is a stable, free-flowing aromatic powder standardized to contain a minimum 30 per cent alpha and iso-alpha acids for tablets and capsules. This anti-inflammatory is derived from hops.

For joints, Arthriblend is an herbal formulation with anti-inflammatory effects. It contains glucosamine sulfate, boswellia, curcuminoids and bioperine for enhanced bioavailability.

TSI Health Sciences
For joints, Pureflex brand glucosamine and chondroitin produced in a GMP-certified facility.

For joint health, glucosamine sulfate sodium, glucosamine sulfate potassium and glucosamine HCl.

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2. Yetley EA, et al. Dietary reference intakes for vitamin D: justification for a review of the 1997 values. Am J Clin Nutr 2009;89:719-727
3. Dawson-Hughes B. Serum 25-hydroxyvitamin D and functional outcomes in the elderly. Am J Clin Nutr 2008;88(suppl):537S-540S.
4. Bischoff-Ferrari HA. Optimal serum 25-hydroxyvitamin D levels for multiple health concerns. Adv Exp Med Biol 2008;624:55-71.
5. Hathcock JN, et al. Risk assessment for vitamin D. Am J Clin Nutr 2007;85:6-18.
6. Vieth R. Critique of the considerations for establishing the tolerable upper intake level for vitamin D: critical need for revision upwards. J Nutr 2006;136:1117-1122.
7. Heron M, et al. Deaths: Final data for 2006. CDC:National Vital Statistics Reports 2009;57(14):Table 10.
8. Bischoff-Ferrari HA, et al. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 2005;293:2257-64.
9. Wicherts IS, et al. Vitamin D status predicts physical performance and its decline in older persons. J Clin Endocrin Metab 2007;92:2058-65.
10. Stewart JW, et al. Serum 25-hydroxyvitamin D is related to indicators of overall physical fitness in healthy postmenopausal women. Menopause 2009 (in press).
11. Mosekilde L. Vitamin D and the elderly. Clin Endocrinol 2005:62:265-281.
12. Avenell A, Gillespie WJ, et al. Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis. The Cochrane Database of Systematic Reviews. 2005, Issue 3, Art. No. CD000227.pub2. 96 pages.
13. Bischoff-Ferrari HA, Zhang Y, et al. Positive association between serum 25-hydroxyvitamin D level and bone density in osteoarthritis. Arthritis Rheum 2005;53:821-826.
14. Oudshoorn C, et al. Higher serum vitamin D3 levels are associated with better cognitive test performance in patients with Alzheimer’s disease. Dement Geriatr Cogn Disord 2008;25:539-543.
15. Ding C, et al. Serum levels of vitamin D, sunlight exposure, and knee cartilage loss in older adults: the Tasmanian older adult cohort study. Arthritis Rheum 2009;60:1381-89.
16. Felson DT, ete al. Low levels of vitamin D and worsening of knee osteoarthritis: results of two longitudinal studies. Arthritis Rheum 2007;56:129-136.
17. Bruyere O, et al. Total joint replacement after glucosamine sulphate treatment in knee osteoarthritis: results of a mean 8-year observation of patients from two previous 3-year, randomized, placebo-controlled trials. Osteoarthritis Cartilage 2008;16:254-260.
18. Kahan A, et al. Long-term effects of chondroitins 4 and 6 sulfate on knee osteoarthritis: the study on osteoarthritis progression prevention, a two-year, randomized, double-blind, placebo controlled trial. Arthritis Rheum 2009;60:524-533.
19. Ernst E. Frankincense: systemic review. Brit Med J 2008;337:a2813.
20. Benito-Ruiz P, et al. A randomized controlled trial on the efficacy and safety of a food ingredient, collagen hydrolysate, for improving joint comfort. Int J Food Sci Nutr 2009 (Epub ahead of print).
21. 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 (Epub ahead of print).
22. RosenbergIH. Sacropenia: origins and clinical relevance. J Nutr 1997;127:990S-991S.
23. Knapen MH, et al. Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporos Intl 2007 Jul;18(7):963-72.
24. Lim WS, et al. Omega 3 fatty acid for the prevention of dementia. Chochrane Database Syst Rev 2006(1):CD005379.
25. MacLean CH, et al. Effects of omega-3 fatty acid on cognitive function with aging, dementia, and neurological diseases. AHRQ Evidence Report #114. 2005.
26. 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;68:1056-61.
27. Zuccala G, et al. Dose-related impact of alcohol consumption on cognitive function in advanced age: results of a multi-center survey. Alcohol Clin Exp Res 2001;25:1743-48.
28. Kiraly SJ, et al. Vitamin D as a neuroactive substance: review. Sci World J 2006;6:125-139.

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