Nutrition and Functionality: “Key Partners in Ageing” · Nutrition and Functionality: “Key...

Nutrition and Functionality: “Key Partners in Ageing”Chairman: Professor Heike Bischoff-Ferrari

Proceedings from the Nestlé Nutrition Institute Satellite Symposium at the XIXth IAGG World Congress of Gerontology and GeriatricsTuesday, 7 July 2009Paris, France

Nestlé Nutrition Institute Satellite Symposium at the XIXth IAGG World Congress of Gerontology and GeriatricsNutrition and Functionality: “Key Partners in Ageing”

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Nutrition and Functionality:

“Key Partners in Ageing”The Nestlé Nutrition Institute was very pleased to host a satellite symposium at the 19th IAGG World Congress of Gerontology and Geriatrics, held on 7 July 2009 in Paris (France), discussing the various ways that nutrition impacts the functionality of the ageing person. Nutritional status is very often an overlooked aspect in the care for the elderly, with weight loss in the elderly accepted as a “normal” part of ageing. This is despite strong data showing that weight loss is correlated with morbidity and mortality. The expert speakers in this symposium discussed the role of antioxidants, vitamin D and oral nutritional supplements to help optimize the ageing process and preserve or regain functionality, which helps to maintain independence and optimise quality of life in the elderly. The evidence is quite clear that nutrition intake and nutritional status play a key role in promoting healthy ageing.

From left: Professor David R Thomas, Professor Heike Bischoff-Ferrari, Professor Luigi Ferrucci


3

Nutrition and functionality: What is the link?

The significance of nutrition in maintaining good health and how good

nutrition leads to healthy ageing is very challenging to demonstrate. The

basic source of food for animals is plants. Plants use sunlight, which is

the ultimate source of energy, to synthesize carbohydrates. Carbohydrates,

when consumed, release energy within the body. At the cellular level, the

mitochondria play a vital role in converting food – mostly carbohydrates and

lipids – into energy.

Free radical theory of ageingDuring mitochondrial metabolism, very dangerous free radicals (eg, hydroxyl

radical) and reactive oxygen species (eg, hydrogen peroxide) are generated.

Hydrogen peroxide, in particular, is capable of leaving the mitochondria and

attacking other parts of the cell in the cytoplasmic and nuclear environ-

ments, where the damage can be extensive. It is believed that the oxidative

damage caused by these molecules on DNA, lipids and proteins ultimately

leads to ageing and age-related disorders (Figure 1).1

Some of the deleterious actions of free radicals may be prevented

by antioxidants. These antioxidants may be intrinsically generated

enzymes or substances derived from nutritional sources. A chronic state

of oxidative stress occurs when there is an imbalance of pro-oxidant and

antioxidant systems.

Antioxidant vitamins and functional outcomesAntioxidant intake may decrease oxidative stress in older people, as

reflected by improvements in age-related decline in functional outcomes.

The Aging in the CHIANTI Area (InCHIANTI) study assessed the corre-

lation of plasma concentrations and daily dietary intakes of antioxidants with

skeletal muscle strength and physical performance in 986 elderly subjects

(≥65 years).2 Plasma levels of tocopherol – both α-tocopherol (p=0.003)

and γ-tocopherol (p=0.04) – were associated with knee extension strength.

Of the dietary vitamins, vitamin C and β-carotene showed positive correla-

tion with knee extension (p=0.02 and p=0.05, respectively) and vitamin C

was significantly associated with physical performance (p=0.04).2

The association between α-tocopherol and the risk of frailty

syndrome was assessed in 827 older persons (≥65 years) from the InCHI-

ANTI study. Low circulating levels of α-tocopherol were found in persons

identified as being pre-frail and frail.3 One longitudinal study evaluated 698

persons (≥65 years) from the InCHIANTI study registry to determine whether

a low serum concentration of micronutrients was associated with a subse-

quent decline in physical function.4 Results showed a strong correlation for

α-tocopherol (p=0.01). These findings suggest that α-tocopherol may be

an important micronutrient associated with the prevention of disability and

frailty in the elderly.

Similarly, serum carotenoids have also been associated with changes

in skeletal muscle strength in the elderly. Hip, knee and grip strength were

measured in 628 participants from the InCHIANTI study population (≥65

years) at baseline and at 6 years. Participants in the lowest versus highest

quartile of total plasma carotenoids at enrollment were at higher risk of

developing poor hip (p=0.004), knee (p=0.005) and grip (p=0.07) muscle

strength at the 6-year follow-up visit.5

Conflicting data on antioxidant efficacyThere are also inconsistent data on the benefits of administering

β-carotenoids. The Alpha-Tocopherol, Beta-Carotene cancer prevention

(ATBC) study reported a 17% (95% confidence interval [CI] 2–33%) higher

incidence of lung cancer and 8% (95% CI 1–15%) higher total mortality

among participants who received β-carotene supplementation compared

with nonrecipients, during a 6-year trial period. Post-trial data showed that

these differences disappeared when supplementation was stopped.6

A recently conducted genome-wide association study found a

common variation in the BCM01 gene, which was associated with higher

levels of beta-carotene and lower levels of the other carotenoids – lyco-

pene, zeaxanthin and lutein.7 This suggests that when only one carotenoid

is artificially administered, as in the case with supplementation, the absorp-

tion of the other carotenoids is prevented because of competition at the

absorption level. However, the human body is complex and when presented

with different carotenoids in the food, it is able to absorb all the nutrients

in a very wide and balanced concentration. Therefore, administering one

Professor Luigi FerrucciChief, Longitudinal Studies Section Clinical Research Branch National Institute on Aging Baltimore, MD, USA

Figure 1. The “Free Radical Theory of Ageing”1


4

molecule of carotenoid is not likely to have a significant effect on the health

of an individual. Ultimately, it is important to remember that it is the overall

concentration of nutrients in the food, rather than just single molecules, that

will have an impact.

ConclusionsExcessive and unopposed oxidative stress may be the main cause of

progressive disability and other adverse manifestations of ageing. Intake

of antioxidants may decrease this oxidative stress, but the available data

on the benefits of antioxidant supplementation are conflicting. However,

antioxidants as part of food are beneficial.

Minimising falls and fractures: What role does nutrition play?

Nutrition plays an important role in maintaining functionality in the elderly.

Impaired functionality may increase the risk of falls and subsequent frac-

tures, a major adverse event in this population. Older individuals (≥65

years) who had suffered previous falls are particularly prone to recurrent

falls, and have a 4-fold increased risk of sustaining fall-related fractures.1

Furthermore, individuals who sustain a fracture are more likely to suffer

subsequent fractures.2 After the age of 75 years, hip fractures are the most

severe and most frequent type of fractures sustained from falls.

Vitamin D supplementation: A desirable strategy for fall and fracture preventionThe key to preventing falls and fractures in the elderly is through early

intervention strategies, possibly through a dual impact on bone and muscle.

There is now a large body of clinical trial data that shows that vitamin

D supplementation is associated with benefits on both of these structural

components; on the one hand, vitamin D improves bone mineral density

and contributes to fracture reduction, and on the other hand, it increases

muscle strength and reduces the risk of falls.

Vitamin D insufficiency in the elderlyThe primary sources of vitamin D in humans are skin exposure to sunlight

and dietary intake.3 However, these sources often do not adequately meet

vitamin D requirements in older individuals, leading to vitamin D insuffi-

ciency and deficiency. In Europe4 and the US5, only <20% and <30% of

older persons, respectively, reach the serum threshold level of 75 nmol/L

for 25-hydroxyvitamin D, which is required for optimal bone health and

fracture reduction. A recent survey of hip fracture patients (>65 years old)

in Switzerland found that less than 5% of patients reached this desired

serum level, and severe vitamin D deficiency, below 30 nmol/L, was present

in 60% of patients.6

Several potential reasons exist for the observed high prevalence of

vitamin D insufficiency among the elderly. Sun exposure may be insufficient

for cutaneous vitamin D production due to3:

Living in northern latitudes•

Winter season•

Having a darker skin tone•

Being institutionalised•

Age-related decrease in the capacity of the skin to produce vitamin D •

Furthermore, it would be impractical, if not impossible, to meet all of

the vitamin D needs through dietary sources, which are largely limited to

oily fish, such as salmon and mackerel. Alternatively, vitamin D supplemen-

tation may be recommended as an effective means for achieving adequate

levels in older persons. In fact, the revised dietary guidelines issued by

Health Canada in 2007 recommend a daily vitamin D supplement of 10 μg

(400 IU) for adults over the age of 50.7

How does vitamin D affect muscle tissue?Vitamin D receptors (VDR) are present in human muscle tissue.8 The bind-

ing of vitamin D to these receptors may lead to de novo protein synthesis

affecting muscle cell growth.9 The importance of vitamin D in muscle devel-

opment has been demonstrated in VDR knockout mice, which show a skel-

etal muscle phenotype with variable and smaller muscle fibres, similar to

humans with severe vitamin D deficiency.10 VDR expression decreases with

age.8 This may in part explain sarcopenia associated with old age and the

resultant adverse outcomes, such as muscle weakness, falls and fractures.

Generally, muscle weakness is also recognised as a clinical sign of severe

vitamin D deficiency, which is reversible with treatment.

There is ample clinical evidence demonstrating the benefits of vita-

min D on muscle structure and function. In a small uncontrolled biopsy

study in postmenopausal women with osteoporosis, the diameter and rela-

tive number of type II muscle fibres increased after 3 months of treatment

with 1-alpha-hydroxyvitamin D.9

References

1. Harman D. J Gerontol 1956;11:298-300.2. Cesari M, et al. Am J Clin Nutr 2004;79:289-294.3. Ble A, et al. J Gerontol A Biol Sci Med Sci 2006;61:278-283.4. Bartali B, et al. JAMA 2008;299:308-315.5. Lauretani F, et al. J Gerontol A Biol Sci Med Sci 2008;63A:376-383.6. The ATBC Study Group. JAMA 2003;290:476-485.7. Ferrucci L, et al. Am J Hum Genet 2009;84:123-133.

Professor Heike Bischoff-FerrariDirector, Centre on Aging and Mobility, University of ZurichDirector, Therapeutic Exercise Sciences,Department of Rheumatology and Institute of Physical Medicine University Hospital ZurichSwitzerland


5

The third National Health and Nutrition Examination Survey (NHANES

III) investigated the association between serum 25-hydroxyvitamin D

concentrations and lower extremity function — an important predictor of

disability, falls and hip fractures in older adults — in 4,100 community-

dwelling older individuals (≥60 years) in the US.11 Lower-extremity function

was assessed using an 8-foot walking-speed test and a timed test of five

repetitions of rising from a chair and sitting down. A significant positive

association was found between 25-hydroxyvitamin D concentrations and

these musculoskeletal functions (Figure 2), independent of activity level,

gender or calcium intake, suggesting that different subgroups of the elderly

population could benefit from maintaining high serum 25-hydroxyvitamin

D levels.11

Nonvertebral and hip fracture prevention with vitamin DThe anti-fracture efficacy of oral vitamin D supplementation in older indi-

viduals (≥65 years) was assessed in a recently published meta-analysis

of 16 double-blind, randomised, controlled trials; the analysis included 12

trials for nonvertebral fractures (n=42,279) and 8 trials for hip fractures

(n=40,886).13 The analysis detected heterogeneity, where the anti-fracture

efficacy of supplemental vitamin D increased significantly with higher

received dose (treatment dose x adherence) or higher achieved serum

25-hydroxyvitamin D levels for both fracture endpoints; a higher received

dose of 482–770 IU/day of supplemental vitamin D reduced nonvertebral

fractures by 20% (pooled relative risk [RR]=0.80; 95% CI 0.72–0.89;

n=33,265 from 9 trials) (Figure 3) and hip fractures by 18% (pooled

RR=0.82; 95% CI 0.69–0.97; n=31,872 from 5 trials), whereas, no fracture

reduction was observed for a received dose of ≤400 IU/day.13

Nonvertebral fracture prevention was present and significant in

all subgroups of the older population, most pronounced in community-

Outcome Complications 6-month mortality

Supplement

Control

Electron Transport Chain (ETC)

NADH Dehydrogenase

complex

H+ H+ H+H+

H+

H+

III

Q IIIC

IV V Fo

Fi

NADH + H

Succinate dehydrogenase complex

B-C1 complex

Cytochrome oxidase complex

ATP synthase

FADH2

0 20 40 60 80 100 120 140 160 180 200 220 240

3.5

4

4.5

0 20 40 60 80 100 120 140 160 180 200 220 240

14

15

16

8-foot walk Repeated sit-to-stand

25-OHD nmol/L 25-OHD nmol/L

Wal

k tim

e (s

)

Tim

e to

sta

nd (s

)

For 482 to 770 IU per day:

WHI 60+Pfeifer 2000

TrivediPfeifer 2008

Dawson-HughesChapuy 2002

LyonsChapuy 1994

Flicker

Combined

0.1 0.5 1.0 5.0

}}

Community-dwelling -29%

Institutionalised -15%

Relative risk

Pooled relative risk all = 0.80 (95% CI; 0.72–0.89)

Favours calcium Favours placebo

0.1 0.5 51 10Relative risk

Prince et al

Reid et al

Bischoff-Ferrari et al

Grant et al

Combined

10

5

0

-5

-10

29

27

25

23

21

19

17

15

Perc

ent c

hang

e in

wei

ght

over

60

days

MNA

® s

core

at 6

0 da

ysControl

p=0.05

-1.73%

56%

13%

44%

87%

40%

74%

Supplement

0.68%

Control

20.8

p<0.01

Supplement

23.5

2,400

2,200

2,000

1,800

1,600

1,400

1,200

1,000

Kcal

s co

nsum

ed

Perc

ent w

eigh

t gai

nRe

lativ

e ris

k of

mor

talit

y

Snack Supplement Snack Supplement

Week 3 Week 6

1,574

1,893

1,545

1,888

• Hospital: 14 trials• Long-term care: 8 trials• Home: 16 trials

3.0

2.6

2.2

1.8

1.4

1.0

Long-term care

1.8%

2.5%

2.3%

Hospital

Home

• 35 reports/3,021 randomised subjects

• 28% reduction in mortality when only undernourished subjects included

1.2

1.1

1

0.9

0.8

0.7

0.6

0.5

0.4

Nourished

0.780.72

Under-nourished

Figure 2. Dose-response for 25-hydroxyvitamin D levels and lower extremity function11


Supplement

Control


NADH Dehydrogenase

complex

H+ H+ H+H+

H+

H+

III

Q IIIC

IV V Fo

Fi

NADH + H


B-C1 complex


ATP synthase

FADH2

0 20 40 60 80 100 120 140 160 180 200 220 240

3.5

4

4.5

0 20 40 60 80 100 120 140 160 180 200 220 240

14

15

16



Wal

k tim

e (s

)

Tim

e to

sta

nd (s

)


WHI 60+Pfeifer 2000

TrivediPfeifer 2008


LyonsChapuy 1994

Flicker

Combined

0.1 0.5 1.0 5.0

}}



Relative risk




Prince et al

Reid et al


Grant et al

Combined

10

5

0

-5

-10

29

27

25

23

21

19

17

15

Perc

ent c

hang

e in

wei

ght

over

60

days

MNA

® s

core

at 6

0 da

ysControl

p=0.05

-1.73%

56%

13%

44%

87%

40%

74%

Supplement

0.68%

Control

20.8

p<0.01

Supplement

23.5

2,400

2,200

2,000

1,800

1,600

1,400

1,200

1,000

Kcal

s co

nsum

ed

Perc

ent w

eigh

t gai

nRe

lativ

e ris

k of

mor

talit

y


Week 3 Week 6

1,574

1,893

1,545

1,888


3.0

2.6

2.2

1.8

1.4

1.0

Long-term care

1.8%

2.5%

2.3%

Hospital

Home



1.2

1.1

1

0.9

0.8

0.7

0.6

0.5

0.4

Nourished

0.780.72

Under-nourished

Figure 3. Nonvertebral fracture reduction at higher received vitamin D dose13

25-OHD, 25-hydroxyvitamin D

Table 1. Supplemental vitamin D (482–770 IU/day) and nonvertebral fracture reduction – primary subgroup analysis13

RCT, Randomised controlled trial

Primary analysis of higher dose RCTs - 20%*

Primary subgroup analysisD3 only D2 only

- 23%*- 10%

Age 65-74Age 75+

- 33%*- 17%*

Community-dwellingInstitutionalised

- 29%*- 15%*

Main effect vitamin D Vitamin D plus calcium

- 21%- 21%*

*significant


6

dwelling older individuals (29%) and those aged 65–74 years (33%) (Table

1).13 Additional calcium supplementation in subjects already receiving high

doses of vitamin D did not enhance the effect of vitamin D in reducing

nonvertebral fractures.

Impact of other micro/macro nutrients on falls and fractures?Apart from vitamin D, evidence-based data on nutrition and fall and fracture

prevention are mainly limited to calcium supplementation. A meta-analysis

of prospective cohort studies and randomised controlled trials assessed the

impact of calcium intake on hip fracture risk.14 Pooled results from four trials

showed no reduction in hip fracture risk with calcium supplementation,

and a possible 64% increase in risk (pooled RR=1.64; 95% CI 1.02–2.64;

n=6,504 with 139 hip fractures) (Figure 4). Pooled analysis of five clinical

trials yielded a neutral effect of calcium supplementation compared with

placebo for any nonvertebral fracture (pooled RR=0.92; 95% CI 0.81–1.05;

n=6,740 with 814 nonvertebral fractures).14

Given the potential adverse effect with respect to hip fractures,

calcium supplementation alone should not be considered for fracture

prevention in clinical practice, but rather an optimal combination of calcium

and vitamin D may be a better strategy. Furthermore, vitamin D given with

dairy products – a natural source of calcium – would confer additional

benefits as they contain protein, a key component of muscle, for increasing

muscle mass and strength.

ConclusionsVitamin D insufficiency and deficiency are highly prevalent in the elderly.

Since vitamin D needs cannot be adequately met with diet or sun expo-

sure, supplementation is essential for maintaining better bone and muscle

health. Supplemental vitamin D has been shown to have a dose-dependent

benefit on reducing fractures in the elderly. Fracture prevention starts at

received vitamin D doses of at least 480 IU/day, with continuous improve-

ments thereafter. The available evidence suggests that a daily dose of

700–1,000 IU/day of supplemental vitamin D should be recommended for

fall and fracture prevention in individuals aged 60 years and older.

Oral nutritional supplementation: Does it make a difference?

As humans age, there is an overall decline in food intake, referred to as the

“anorexia of ageing”, which can contribute to malnutrition and weight loss.

Ten percent of older men and 20% of older women have intakes of protein

below the US recommended daily allowance (RDA) and 50% of older adults

have intakes of vitamins and minerals less than the RDA.1 Furthermore,

16–18% of community-dwelling elderly persons consume <1,000 kcal/day.

Weight loss is a devastating consequence in the elderly, as it carries an

increased risk of mortality.2 Hence, oral nutritional supplementation may

be beneficial in older individuals for promoting weight gain and meeting

essential nutritional requirements.

Oral nutritional supplements can be divided into two categories:

Nutritionally complete: Suitable as a sole source of nutrition•

Nutritionally incomplete: Not suitable as a sole source of nutrition, only •

as a supplement to food intake

Do oral nutritional supplements improve nutritional status and other outcomes?An observational, prospective, cohort study assessed the impact of admin-

istering oral nutritional supplements on the nutritional status of 378 elderly

(>70 years) malnourished patients over 12 months.3 Nutritional status

was determined at baseline and throughout the study using the Mini Nutri-

tional Assessment (MNA®) scale. Over time, the MNA® score improved


Supplement

Control


NADH Dehydrogenase

complex

H+ H+ H+H+

H+

H+

III

Q IIIC

IV V Fo

Fi

NADH + H


B-C1 complex


ATP synthase

FADH2

0 20 40 60 80 100 120 140 160 180 200 220 240

3.5

4

4.5

0 20 40 60 80 100 120 140 160 180 200 220 240

14

15

16



Wal

k tim

e (s

)

Tim

e to

sta

nd (s

)


WHI 60+Pfeifer 2000

TrivediPfeifer 2008


LyonsChapuy 1994

Flicker

Combined

0.1 0.5 1.0 5.0

}}



Relative risk




Prince et al

Reid et al


Grant et al

Combined

10

5

0

-5

-10

29

27

25

23

21

19

17

15

Perc

ent c

hang

e in

wei

ght

over

60

days

MNA

® s

core

at 6

0 da

ysControl

p=0.05

-1.73%

56%

13%

44%

87%

40%

74%

Supplement

0.68%

Control

20.8

p<0.01

Supplement

23.5

2,400

2,200

2,000

1,800

1,600

1,400

1,200

1,000

Kcal

s co

nsum

ed

Perc

ent w

eigh

t gai

nRe

lativ

e ris

k of

mor

talit

y


Week 3 Week 6

1,574

1,893

1,545

1,888


3.0

2.6

2.2

1.8

1.4

1.0

Long-term care

1.8%

2.5%

2.3%

Hospital

Home



1.2

1.1

1

0.9

0.8

0.7

0.6

0.5

0.4

Nourished

0.780.72

Under-nourished

Figure 4. Calcium supplementation vs placebo on hip fracture risk14

Professor David R ThomasProfessor of MedicineDivision of Geriatric MedicineSaint Louis University Medical CenterSaint Louis, MO, USA

References

1. Pluijm SM, et al. Osteoporos Int 2006;17:417-425.2. Center JR, et al. JAMA 2007;297: 387-394.3. Chen TC, et al. Arch Biochem Biophys 2007;460:213-217.4. van der Wielen RP, et al. Lancet 1995;346:207-210.5. Bischoff-Ferrari HA, et al. J Bone Miner Res 2009;24:935-942.6. Bischoff-Ferrari HA, et al. Bone 2008;42:597-602.7. Health Canada 2007 Web site. Available at: http://www.hc-sc.gc.ca/fn-an/food-

guide-aliment/context/evid-fond/vita_d-eng.php. Accessed 3 August 2009.8. Bischoff-Ferrari HA, et al. J Bone Miner Res 2004;19:265-269.9. Sorensen OH, et al. Clin Sci (Lond) 1979;56:157-161.10. Endo I, et al. Endocrinology 2003;144:5138-5144.11. Bischoff-Ferrari HA, et al. Am J Clin Nutr 2004;80:752-758.12. Bischoff-Ferrari HA, et al. BMJ In press.13. Bischoff-Ferrari HA, et al. Arch Intern Med 2009;169:551-561.14. Bischoff-Ferrari HA, et al. Am J Clin Nutr 2007;86:1780-1790.


7

significantly more in patients who were routinely prescribed nutritional

supplements than in those who rarely received the supplements (p<0.01).3

In another clinical trial, 80 patients, aged >75 years and at risk of

undernutrition, were randomised to receive either oral nutritional supple-

mentation or no supplementation during hospitalisation and after discharge,

for a total duration of 60 days.4 Nutritional status and body weight were

assessed at baseline and at the end of study. Oral supplementation main-

tained body weight throughout the study period while no supplementation

resulted in weight loss (Figure 5). The mean percent weight changes from

baseline in the two groups were statistically significant (p=0.05). Further-

more, at the end of study, the MNA® scores were higher in the supple-

mented group than in the control group (p<0.01).4

In one study, 59 elderly patients (mean age 82 years) with femo-

ral neck fractures were randomised to receive either a daily oral nutri-

tion supplement or no supplement for a mean of 32 days. Overall, clinical

outcomes were much improved in the supplemented group, with lower

complication rates and fewer deaths than the control group (Figure 6).5

Another study compared the improvements in body composition

from liquid nutritional supplementation and placebo over 6 months in

68 elderly subjects (mean age 82 years) with a low body mass index

(≤25 kg/m2).6 After 6 months, the supplement group had gained more

weight than the placebo group (p=0.03). The body mass index also improved

in the supplemented group compared with the placebo group. Furthermore,

supplementation did not affect energy intake from regular meals, suggest-

ing that it resulted in additional energy intake; the daily energy and protein

intake contributed by the dietary supplement consisted of 250 kcal and

8.75 g, respectively.6

Do oral nutritional supplements decrease regular food intake?A common concern with oral nutritional supplements is their impact on

regular food and caloric intake and whether they simply substitute regu-

lar food, and thus have no net effect. However, clinical evidence actually

shows improvement in caloric intake in elderly individuals treated with such

supplements.

A 6-week, randomised, controlled trial conducted in 91 elderly resi-

dents of long-term care facilities compared the effects of nutritional supple-

mentation and extra food snacks in between meals.7 When assessed at

weeks 3 and 6, the overall caloric intake was significantly increased in the

supplemented group compared with the food-snack group (Figure 7).

Similarly, another randomised controlled study assessed the effect

of oral nutritional supplementation on daily energy intake, body weight

and nutritional status in 88 nursing home residents (≥65 years) over

60 days.8 At baseline, subjects were grouped according to their MNA®

scores: well-nourished (>24), at-risk (17–23.5) and malnourished (<17).

The well-nourished group (group A) received no supplementation. The

at-risk group was randomised to either no oral supplementation (group B)

or oral supplementation (group C). The malnourished group received daily

oral nutritional supplementation (group D). The total energy intake (kcal)

and protein intake (g) on day 60 versus day 0 were significantly increased in

both groups that received supplementation (p<0.001), whereas there was

very little change in the groups that did not receive any supplements (total


Supplement

Control


NADH Dehydrogenase

complex

H+ H+ H+H+

H+

H+

III

Q IIIC

IV V Fo

Fi

NADH + H


B-C1 complex


ATP synthase

FADH2

0 20 40 60 80 100 120 140 160 180 200 220 240

3.5

4

4.5

0 20 40 60 80 100 120 140 160 180 200 220 240

14

15

16



Wal

k tim

e (s

)

Tim

e to

sta

nd (s

)


WHI 60+Pfeifer 2000

TrivediPfeifer 2008


LyonsChapuy 1994

Flicker

Combined

0.1 0.5 1.0 5.0

}}



Relative risk




Prince et al

Reid et al


Grant et al

Combined

10

5

0

-5

-10

29

27

25

23

21

19

17

15

Perc

ent c

hang

e in

wei

ght

over

60

days

MNA

® s

core

at 6

0 da

ysControl

p=0.05

-1.73%

56%

13%

44%

87%

40%

74%

Supplement

0.68%

Control

20.8

p<0.01

Supplement

23.5

2,400

2,200

2,000

1,800

1,600

1,400

1,200

1,000

Kcal

s co

nsum

ed

Perc

ent w

eigh

t gai

nRe

lativ

e ris

k of

mor

talit

y


Week 3 Week 6

1,574

1,893

1,545

1,888


3.0

2.6

2.2

1.8

1.4

1.0

Long-term care

1.8%

2.5%

2.3%

Hospital

Home



1.2

1.1

1

0.9

0.8

0.7

0.6

0.5

0.4

Nourished

0.780.72

Under-nourished

Figure 6. Dietary supplementation improves clinical outcomes in elderly patients with femoral neck fractures5


Supplement

Control


NADH Dehydrogenase

complex

H+ H+ H+H+

H+

H+

III

Q IIIC

IV V Fo

Fi

NADH + H


B-C1 complex


ATP synthase

FADH2

0 20 40 60 80 100 120 140 160 180 200 220 240

3.5

4

4.5

0 20 40 60 80 100 120 140 160 180 200 220 240

14

15

16



Wal

k tim

e (s

)

Tim

e to

sta

nd (s

)


WHI 60+Pfeifer 2000

TrivediPfeifer 2008


LyonsChapuy 1994

Flicker

Combined

0.1 0.5 1.0 5.0

}}



Relative risk




Prince et al

Reid et al


Grant et al

Combined

10

5

0

-5

-10

29

27

25

23

21

19

17

15

Perc

ent c

hang

e in

wei

ght

over

60

days

MNA

® s

core

at 6

0 da

ysControl

p=0.05

-1.73%

56%

13%

44%

87%

40%

74%

Supplement

0.68%

Control

20.8

p<0.01

Supplement

23.5

2,400

2,200

2,000

1,800

1,600

1,400

1,200

1,000

Kcal

s co

nsum

ed

Perc

ent w

eigh

t gai

nRe

lativ

e ris

k of

mor

talit

y


Week 3 Week 6

1,574

1,893

1,545

1,888


3.0

2.6

2.2

1.8

1.4

1.0

Long-term care

1.8%

2.5%

2.3%

Hospital

Home



1.2

1.1

1

0.9

0.8

0.7

0.6

0.5

0.4

Nourished

0.780.72

Under-nourished

Figure 7. Nutrition supplementation increases caloric intake in institutionalised elderly people7


Supplement

Control


NADH Dehydrogenase

complex

H+ H+ H+H+

H+

H+

III

Q IIIC

IV V Fo

Fi

NADH + H


B-C1 complex


ATP synthase

FADH2

0 20 40 60 80 100 120 140 160 180 200 220 240

3.5

4

4.5

0 20 40 60 80 100 120 140 160 180 200 220 240

14

15

16



Wal

k tim

e (s

)

Tim

e to

sta

nd (s

)


WHI 60+Pfeifer 2000

TrivediPfeifer 2008


LyonsChapuy 1994

Flicker

Combined

0.1 0.5 1.0 5.0

}}



Relative risk




Prince et al

Reid et al


Grant et al

Combined

10

5

0

-5

-10

29

27

25

23

21

19

17

15

Perc

ent c

hang

e in

wei

ght

over

60

days

MNA

® s

core

at 6

0 da

ysControl

p=0.05

-1.73%

56%

13%

44%

87%

40%

74%

Supplement

0.68%

Control

20.8

p<0.01

Supplement

23.5

2,400

2,200

2,000

1,800

1,600

1,400

1,200

1,000

Kcal

s co

nsum

ed

Perc

ent w

eigh

t gai

nRe

lativ

e ris

k of

mor

talit

y


Week 3 Week 6

1,574

1,893

1,545

1,888


3.0

2.6

2.2

1.8

1.4

1.0

Long-term care

1.8%

2.5%

2.3%

Hospital

Home



1.2

1.1

1

0.9

0.8

0.7

0.6

0.5

0.4

Nourished

0.780.72

Under-nourished

Figure 5. Oral nutritional supplementation prevents malnutrition in older people during and after hospitalisation4

MNA®, Mini Nutritional Assessment


8

energy intake in group C, 1,815 vs 1,558 and in group D, 1877 vs 1489;

protein intake in group C, 81.1 vs 57.4 and in group D, 85.8 vs 52.9).8 These

changes in energy intake were paralleled by changes in body weight in all

four groups.

A meta-analysis also documented increased daily protein and energy

intake with nutritional supplementation in 29 studies that used a variety of

methods and formulations.9

Is the timing of the supplement important?There is insufficient evidence on the effect of timing of nutritional supple-

mentation on outcomes in the elderly. However, one study suggested that

administration of supplements between meals instead of with meals may

increase energy consumption.10

Meta-analytical studies of protein and energy supplementation A number of recently published meta-analytical studies have focused on

the effectiveness of oral protein and energy supplements versus placebo

or no supplementation in improving clinical and nutritional outcomes in

older people.

One review included 34 trials that involved 3,021 randomised

subjects.9 Nutritional supplementation was associated with a mean weight

gain of 2.3% (95% CI 1.9–2.7%). Mortality was reduced in the supple-

mented group compared with the control group (RR=0.74; 95% CI 0.59–

0.92) based on data from 32 trials.9 However, morbidity was not affected

by supplementation.

Another meta-analysis compared the percent weight gain among

patients living at home, and in long-term care and hospital-settings.11

Whilst supplemented patients in all three settings showed significant

improvements, patients in long-term care and at home benefited the most

(Figure 8).11

This meta-analysis also evaluated the survival benefits of nutritional

supplementation in specific subgroups of patients. Improved survival was

associated with11:

Low baseline nutrition status•

– The benefit for mortality was statistically significant in undernour-

ished subjects but not in nourished subjects (Figure 9).

Age >75 years•

Energy intake >400 kcal/day•

Duration of intervention >35 days•

Patient health (being unwell)•

Hospital setting (vs community)•

Presence of geriatric conditions •

Thus, nutritional therapy will yield the highest efficacy when specific

geriatric populations are targeted. The MNA® will play a pivotal role in

nutritional screening for identifying the ideal candidates for nutritional

therapy. Future trials should focus on ways to demonstrate improvements

in strength, function and quality of life.

ConclusionsClinical data for oral nutritional supplementation in the elderly demonstrate

weight gain and improvements in nutritional status. Nutritional supplemen-

tation does not decrease regular food intake, but actually increases protein

and caloric intake in elderly persons. Oral nutritional supplements also

appear to have a benefit on mortality. This benefit increases when specific

subgroups of the elderly are targeted; older, undernourished, and hospital-

ised subjects, as well as those who are unwell or have geriatric conditions,

benefit most. A greater energy intake and longer duration of supplementa-

tion also reduce mortality.

References

1. Thomas DR. In: Schmitz PG, Martin KJ, eds. Internal Medicine. Just the facts. New York: McGraw Hill; 2008.

2. Newman AB, et al. J Am Geriatr Soc 2001;49:1309-1318.3. Arnaud-Battandier F, et al. Clin Nutr 2004;23:1096-1103.4. Gazzotti C, et al. Age Ageing 2003;32:321-325.5. Delmi M, et al. Lancet 1990;335:1013-1016.6. Wouters-Wesseling W, et al. Clin Nutr 2003;22:371-377.7. Turic A, et al. J Am Diet Assoc 1998:1457-1459. 8. Lauque S, et al. Age Ageing 2000;29:51-56.9. Milne AC, et al. Cochrane Database Syst Rev 2005;2:CD003288.10. Wilson MM, et al. Am J Clin Nutr 2002;75:944-947.11. Milne AC, et al. Ann Intern Med 2006;144:37-48.


Supplement

Control


NADH Dehydrogenase

complex

H+ H+ H+H+

H+

H+

III

Q IIIC

IV V Fo

Fi

NADH + H


B-C1 complex


ATP synthase

FADH2

0 20 40 60 80 100 120 140 160 180 200 220 240

3.5

4

4.5

0 20 40 60 80 100 120 140 160 180 200 220 240

14

15

16



Wal

k tim

e (s

)

Tim

e to

sta

nd (s

)


WHI 60+Pfeifer 2000

TrivediPfeifer 2008


LyonsChapuy 1994

Flicker

Combined

0.1 0.5 1.0 5.0

}}



Relative risk




Prince et al

Reid et al


Grant et al

Combined

10

5

0

-5

-10

29

27

25

23

21

19

17

15

Perc

ent c

hang

e in

wei

ght

over

60

days

MNA

® s

core

at 6

0 da

ysControl

p=0.05

-1.73%

56%

13%

44%

87%

40%

74%

Supplement

0.68%

Control

20.8

p<0.01

Supplement

23.5

2,400

2,200

2,000

1,800

1,600

1,400

1,200

1,000

Kcal

s co

nsum

ed

Perc

ent w

eigh

t gai

nRe

lativ

e ris

k of

mor

talit

y


Week 3 Week 6

1,574

1,893

1,545

1,888


3.0

2.6

2.2

1.8

1.4

1.0

Long-term care

1.8%

2.5%

2.3%

Hospital

Home



1.2

1.1

1

0.9

0.8

0.7

0.6

0.5

0.4

Nourished

0.780.72

Under-nourished

Figure 8. Weight gain with protein and energy supplementation in older people11


Supplement

Control


NADH Dehydrogenase

complex

H+ H+ H+H+

H+

H+

III

Q IIIC

IV V Fo

Fi

NADH + H


B-C1 complex


ATP synthase

FADH2

0 20 40 60 80 100 120 140 160 180 200 220 240

3.5

4

4.5

0 20 40 60 80 100 120 140 160 180 200 220 240

14

15

16



Wal

k tim

e (s

)

Tim

e to

sta

nd (s

)


WHI 60+Pfeifer 2000

TrivediPfeifer 2008


LyonsChapuy 1994

Flicker

Combined

0.1 0.5 1.0 5.0

}}



Relative risk




Prince et al

Reid et al


Grant et al

Combined

10

5

0

-5

-10

29

27

25

23

21

19

17

15

Perc

ent c

hang

e in

wei

ght

over

60

days

MNA

® s

core

at 6

0 da

ysControl

p=0.05

-1.73%

56%

13%

44%

87%

40%

74%

Supplement

0.68%

Control

20.8

p<0.01

Supplement

23.5

2,400

2,200

2,000

1,800

1,600

1,400

1,200

1,000

Kcal

s co

nsum

ed

Perc

ent w

eigh

t gai

nRe

lativ

e ris

k of

mor

talit

y


Week 3 Week 6

1,574

1,893

1,545

1,888


3.0

2.6

2.2

1.8

1.4

1.0

Long-term care

1.8%

2.5%

2.3%

Hospital

Home



1.2

1.1

1

0.9

0.8

0.7

0.6

0.5

0.4

Nourished

0.780.72

Under-nourished

Figure 9. Mortality by nutrition status11

Nutrition and Functionality: “Key Partners in Ageing” · Nutrition and Functionality: “Key...

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