Equal Amounts of Protein at Breakfast, Lunch and Dinner May Reduce Functional Decline from Sarcopenia

Sarcopenia is a major component in the development of frailty within the elderly [1], increasing risk of falls and affecting the ability to undertake basic tasks of daily living. Loss of muscular mass and strength begins as early as 30 years of age, and is determined by both peak muscle mass attained in early life and the subsequent rate of muscle loss [2]. High protein intake is frequently reported to delay progression of sarcopenia, but a recent study by Farsijani et al. suggested that distribution of protein intake between meals is also of significance [3]. From discussing their findings within wider research, it has bee concluded that evenly distributing daily protein throughout the day, consuming a portion of at least 30g of high quality protein at breakfast, lunch and dinner, may increase muscle mass and strength within the elderly. It could also be recommended that young and middle-aged adults follow similar advice to maximise peak muscle mass, so that the natural losses that occur with age do not reach the threshold for impaired functional capacity.

Sarcopenia is an age associated condition resulting from the progressive loss of skeletal muscle mass and strength [4]. 30% of those over 60 years and 50% of those over 80 years suffer from sarcopenia [5], which reduces physical mobility, increases risk of falls [6] and reduces capacity to maintain a healthy lifestyle [7]. Additionally, the role of skeletal muscle in lipid oxidation and as a disposal site for glucose [8] may increase risk of chronic disease such as type 2 diabetes.

After the age of 35 years, there is said to be a 1-2% annual loss of muscle mass and a 1.5% annual decline in strength, the latter increasing to 3% beyond the age of 60 [9]. By the time a person reaches the age of 75-80 years, lean muscle can be as little as 25%, with most notable change being in the lower limbs [7]. The loss in muscle mass primarily occurs within type 2 muscle fibres due to atrophy, fibre necrosis, fibre type grouping and a reduction in satellite cell content [7]. The relative elevation in type 1 fibre density therefore preserves muscular endurance but causes reduced strength [10].

Skeletal muscle is in a constant state of flux. Protein degradation and synthesis, as is mediated by mTOR signalling and translation initiation [11], occur in response to feeding, fasting and exercise [12]. A loss of muscle mass results from a negative nitrogen balance, stimulating protein catabolism [13]. The cause of the imbalance and consequential muscular decline is multifactorial. Reduced anabolic hormone production with age, such as growth hormone (GH), insulin-like growth factor (IFG-1) and testosterone, may lead to changes in body composition, characterised by an increase in visceral fat and decrease in lean body mass. Moreover, dysregulation of cytokine secretion triggers inflammation and muscle wasting due to increased myofibrillar protein degradation, as well as decreased synthesis from TNF-α inhibition of ranslation initiation [10].

However, as basal protein synthesis rates do not differ between the young and the elderly [7], it is thought the focus in sarcopenia prevention should be on the muscle protein synthesis response to anabolic stimuli, particularly food and physical activity. Exercise influences muscle protein anabolism [14] by activating the mTOR pathway [5], working synergistically with dietary protein to increase response to intake and cause hypertrophy [6]. Despite this, the ability to perform physical activity can be compromised within the elderly, especially once degenerative loss of muscle mass and strength has occurred, resulting in the chronic imbalance between muscle synthesis and breakdown [5] in favour of catabolism. Consequently, diet is likely to be a key factor in age-related muscle mass decline, particularly as protein turnover in skeletal muscle is highly responsive to nutrient intake [7]. Food consumption is estimated to decline by 35% between the ages of 40 and 70 years as a result of ‘anorexia of ageing’, where various physiological, psychological and social factors affect appetite and food intake [2]. It is therefore likely to be common for requirements to not be met. Of particular interest is protein as a positive nitrogen balance relies on intake of all essential amino acids in sufficient quantities. It has previously been discussed that daily protein intake for the elderly in excess of average requirements [15] offers benefits to musculoskeletal health, however it is estimated that it may need to be as much as 1.2-1.6g/kg/day to promote muscle protein anabolism [16].

Guidelines on the quantity of dietary protein required are frequently, and fairly consistently, discussed within the literature, but recent studies conducted by Farsijani et al. have hypothesised that timing of protein intake may be of equal, if not greater, importance to muscle mass and strength [3][17]. Typically, protein consumption is skewed towards the evening, with breakfast in being a more carbohydrate dominated meal [18]. This review will discuss the research by Farsijani et al.  into the association between daily protein distribution and decline in muscular strength [3] in the context of wider research to determine whether extending recommendations relating to protein intake in the elderly to ‘per meal’ advice could reduce the rate of functional deterioration so that independence, mobility and quality of life can be maintained.

Method

Study population

Participants were independently living healthy men and women from the NuAge study. Anthropometric measurements including midupper arm muscle area (MAMA), tricep skin fold thickness were taken at baseline (T0) and annually over the 3-year follow up period.

Dietary assessment

Three 24-hour dietary recalls were conducted at T0 and at the second year of follow up (T2).

Measures of muscle strength and functional mobility

Physical performance tests were conducted at T0 and annually throughout the 3-year follow up period. Handgrip, and arm and leg strength were measured using a dynamometer, with subjects assigned a score of 1 (worst) to 4 (best) for each based on sex-specific quartiles. The three scores were summed to a composite score of muscle strength out of 12. Functional mobility was assessed by the ‘Time Up and Go’ test (TUG), chair stand and walking speed at normal and fastest pace. A mobility function composite score was calculated in a similar manner and was out of 16.

Statistical analysis

Changes in subject characteristics over follow up were assessed. Energy-adjusted protein intake was calculated and mealtime protein distribution ascertained using the protein CV, with lower calculated protein CV values indicating evenness. Results were grouped into quartiles.

Nutrient intake at T1 and T3 were estimated using dietary assessment data from T0 and T2. Analysis was conducted using both the two collected data points and over the estimated four year period.

Results

Subject characteristics

1741 participants aged 68 to 82 years were studied. Cognitive status declined over the 3-year period and body weight decreased in both sexes.

Results of dietary intake

Men had a higher overall energy and protein intake but there was no difference in energy-adjusted protein intake. Mealtime protein distribution did not differ between men and women. No significant changes were observed between T0 and T2. Total daily protein intake did not differ based on quartile of protein CV for men, and was slightly less in the highest quartile, reflecting the most uneven distribution, in women.

Results of muscle strength and functional mobility

Composite muscle strength score declined over 3-years. Performance in the normal walking test by men remained unchanged over the 3 years, but deterioration in all other measures of functional mobility was observed for both sexes. There was a 3-year decline in the mobility composite score similar in men and women. The 3-year decline in mobility score was smaller than the decline in muscle strength score.

Results of statistical analysis

Before and after adjustment, a more even protein intake distribution was associated with a higher muscle strength score in men and women. There was a positive association between muscle strength score and energy-adjusted protein intake in women, but the trend was not significant in men. Cognitive status was positively associated with muscle strength score. Deterioration in muscle strength over time was not associated with protein distribution.

Functional mobility score was positively associated with a more even protein distribution in men, but was attenuated after adjustment for covariates. Protein distribution was not associated with functional decline over time. 

Discussion

Farsijani et al. concluded that a more even protein distribution was associated with increased muscular strength [3]. A 25% greater stimulation of muscle protein synthesis over a 24-hour period has been reported in response to following a dietary pattern with protein evenly distributed between breakfast, lunch and dinner compared to one skewed towards the evening [18]. Ingestion of protein causes hyperaminoacidemia, which affects cellular signalling [19], stimulates a transient rise in protein synthesis [6], and suppresses breakdown [7]. Additionally, dietary protein increases circulating IGF-1, further inducing anabolism [20]. It has been suggested that maximum anabolic effect is observed when equal portions of protein are consumed as part of each of the three meals per day separated by 4-5 hours [8], which may facilitate effective protein synthesis as mTOR activation occurs within 30 minutes of consumption, then synthesis is at a maximum at 60-90 minutes, with a decline 2-3 hours post meal for muscle recovery [11].

However, within the elderly it has been suggested that protein portions should be in excess of 30g at every meal [19] as slowed metabolism, reduced absorption and elevated amino acid uptake in the splanchnic area occur [7], reducing amino acid availability for protein synthesis. Additionally, age is thought to reduce anabolic efficiency of skeletal muscle [5], with protein synthesis being less responsive to amino acid ingestion [21]. The cause of this ‘anabolic resistance’ remains uncertain, but is hypothesised to be a consequence of impaired phosphorylation of mTOR mediated signalling proteins or a decline in processes related to inflammation [6]. Nonetheless, it means that consumption of up to 70% more protein may be required by older adults [22] to achieve maximum mTOR signalling and activate mRNA translation for protein synthesis [11].

Despite the high anabolic threshold, there is no benefit of protein intake in excess of the amount required for maximum mTOR signalling [11] as there is no physiological storage mechanism for excess dietary amino acids. Instead, they are deaminated to liberate a carbon skeleton for gluconeogenesis or fatty acid synthesis, and the amino group is excreted as urea. This offers some explanation as to the association between even protein distribution and greater muscle protein synthesis due to the anabolic effect of an evening meal being unable to make up for lack of protein consumption throughout the rest of the day [18]. Additionally, ingesting high quantities of protein increases protein losses in the fasted state [23], an effect that could be reduced by distributing intake between three meals.

It should also be of concern that the protein consumed is of high quality. Animal sources, such as meat, poultry, eggs, fish and milk, provide all nine essential amino acids, whereas vegetable proteins like legumes and soy are deficient in one or more [24], limiting the extent to which positive nitrogen balance can be achieved. More specifically, animal proteins are high in leucine, the main regulator of the mTOR signal pathway [19]. As the liver does not degrade branched chain amino acids such as leucine [11], dietary intake determines the response and the extent of translation initiation [19]. It has been found that coingestion of leucine with casein increases synthesis rate [14], and that >3.5g/meal may overcome the high anabolic threshold in the elderly [24]. Nonetheless, it would not be suggested for free leucine supplements to be utilised as this can result in the desynchronization between the leucine signal and rise in amino acids meaning stimulation of anabolism may not be translated into substantial muscle protein synthesis [25].

Finally, Bollwein et al. reported that frail elderly or those with slower walking speed had a dietary pattern featuring more uneven protein distribution, suggesting that the effect on muscle synthesis may result in functional decline [23]. In contrast, although Farsijani et al. observed an association between muscular strength and protein intake distribution, no effect on functional mobility score was observed [3]. Loss of functional ability is thought to be affected by individual differences in the rate of loss of muscle mass, age at which muscle mass declines, and an individual’s peak muscle mass [6], as attained in early life [2]. It may therefore be that the degenerative extent of sarcopenia is determined by lifestyle in middle age [18] and that intervention should be focussed on those aged 40-60 years to maximise lean body mass [14] and prevent muscular decline occurring to a point where functionality is limited.

Impact

To conclude, discussion of the study by Farsijani et al. within wider research has reinforced the conclusion that a more even protein distribution throughout the day is likely to result in improved muscular strength [3] due to greater protein synthesis being observed within the elderly than from a dietary pattern with protein intake skewed towards dinner. It could therefore be recommended that elderly individuals consume a portion of protein at each meal. This should primarily be from high quality protein sources, particularly of animal origin, to supply sufficient quantities of all essential amino acids and provide leucine to regulate mTOR activation. Additionally, it would be advised for each portion of protein to be approximately 30g to meet the anabolic threshold of skeletal muscle. Adults tend to consume three times as much protein at dinner than at breakfast [18] despite protein consumption being essential to alleviate the catabolic state resulting from the overnight fast [19]. This suggests it to be of greatest importance to focus nutritional guidance on ways to incorporate protein into breakfast which could simply involve the inclusion of eggs, milk, yoghurt or wholegrain bread.

The lack of a proven association with functional decline indicates that this recommendation should not be limited to the elderly, and that middle-aged individuals may be able to slow the rate of loss of muscle mass and strength by making such dietary changes. Furthermore, younger individuals may benefit long term from even protein distribution by maximising peak muscle mass to potentially prevent degenerative sarcopenia in later life.

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[1] Rolland, Y., Czerwinski, S., Abellan van Kan, G., Morley, J.E., Cesari, M., Onder, G., Woo, J., Baumgartner, R., Pillard, F., Boirie, Y., Chumlea, W.M.C., Vellas, B. (2008) Sarcopenia: It’s assessment, etiology, pathogenesis, consequences and future perspectives. Journal of Nutrition, Health and Ageing, 12(7), 433-450.

[2] Robinson, S., Cooper, C., Sayer, A.A. (2012) Nutrition and sarcopenia: A review of the evidence and implications for preventive strategies. Journal of Aging Research, Article ID 510801.

[3] Farsijani, S., Payette, H., Morais, J.A., Shatenstein, B., Gaudreau, P., Chevalier, S. (2017) Even mealtime distribution of protein intake is associated with greater muscle strength, but not with 3-y physical function decline, in free-living older adults: The Quebec longitudinal study on Nutrition as a Determinant of Successful Aging (NuAge study). The American Journal of Clinical Nutrition, 106, 113-124.

[4] Beasley, J.M., Shikany, J.M., Thomson, C.A. (2013) The role of dietary protein intake in the prevention of sarcopenia of aging. Nutrition in Clinical Practice, 28(6), 684-690.

[5] Paddon-Jones, D., Rasmussen, B.B. (2010) Dietary protein recommendations and the prevention of sarcopenia. Current Opinion in Clinical Nutrition & Metabolic Care, 15(2), 132-137.

[6] Breen, L., Phillips, S.M. (2011) Skeletal muscle protein metabolism in the elderly: Interventions to counteract the ‘anabolic resistance’ of ageing. Nutrition & Metabolism, 8(68).

[7] Koopman, R., van Loon, L.J.C. (2009) Aging, exercise, and muscle protein metabolism. Journal of Applied Physiology, 106(6), 2040-2048.

[8] Loenneke, J.P., Pujol, T.J. (2011) Sarcopenia: An emphasis on occlusion training and dietary protein. Hippokratia, 15(2), 132-137.

[9] Calvani, R., Miccheli, A., Landi, F., Bossola, M., Cesari, M., Leeuwenburgh, C., Sieber, C.C., Bernabei, R., Marzetti, E. (2013) Current nutritional recommendations and novel dietary strategies to manage sarcopenia. The Journal of Frailty & Aging, 2(1), 38-53.

[10] Boirie, Y. (2009) Physiopathological mechanism of sarcopenia. Journal of Nutrition, Health and Aging, 13, 717-723.

[11] Layman, D.K., Anthony, T.G., Rasmussen, B.B., Adams, S.H., Lynch, C.J., Brinkworth, G.D., Davis, T.A. (2015) Defining meal requirements for protein to optimize metabolic roles of amino acids. The American Journal of Clinical Nutrition, 101(6), 1330S-1338S.

[12] Rose, A.J., Richter, E.A. (2009) Regulatory mechanisms of skeletal muscle protein turnover during exercise. Journal of Applied Physiology, 106(5), 1702-1711.

[13] Dickerson, R.N. (2016) Nitrogen balance and protein requirements for critically ill older patients. Nutrients, 8(4), 226.

[14] Paddon-Jones, D., Campbell, W.W., Jacques, P.F., Kritchevsky, S.B., Moore, L.L., Rodriguez, N.R., van Loon, L.J.C. (2015) Protein and healthy aging. The American Journal of Clinical Nutrition, 101(6), 1339S-1345S.

[15] Dorrington, N. (2017) Amount and source of protein affects risk of osteoporosis in older adults. URL: https://studentnutritionist.blogspot.co.uk/2017/02/sufficientprotein-is-essential-for_18.html [9th July 2017]

[16] Paddon-Jones, D., Leidy, H. (2014) Dietary protein and muscle in older persons. Current Opinions in Clinical Nutrition and Metabolic Care, 17(1), 5-11.

[17] Farsijani, S., Morais, J.A., Payette, H., Gaudreau, P., Shatenstein, B., Gray-Donald, K., Chevalier, S. (2016) Relation between mealtime distribution of protein intake and lean mass loss in free-living older adults of the NuAge study. The American Journal of Clinical Nutrition, 104(3), 694-703.

[18] Mamerow, M.M., Mettler, J.A., English, K.L., Casperson, S.L., Arentson-Lantz, E., Sheffield-Moore, M., Layman, D.K., Paddon-Jones, D. (2014) Dietary protein distribution positively influences 24-h muscle protein synthesis in healthy adults. Journal of Clinical Nutrition, 144(6), 876-880.

[19] Layman, D.K. (2009) Dietary guidelines should reflect new understandings about adult protein needs. Nutrition & Metabolism, 6(12).

[20] Gaffney-Stomberg, E., Insogna, K.L., Rodriguez, N.R., Kerstetter, J.E. (2009) Increasing dietary protein requirements in elderly people for optimal muscle and bone health. Journal of the American Geriatrics Society, 57(6), 1073-1079.

[21] Katsanos, C.S., Kobayashi, H., Sheffield-Moore, M., Aarsland, A., Wolfe, R.R. (2005) Aging is associated with diminished accretion of muscle proteins after the ingestion of a small bolus of essential amino acids. The American Journal of Clinical Nutrition, 82(5), 1065-1073.

[22] Kim, I-Y., Shutzler, S., Schrader, A., Spencer, H., Kortebein, P., Deutz, N.E.P., Wolfe, R.R., Ferrando, A.A. (2014) Quantity of dietary protein intake, but not pattern of intake, affects net protein balance primarily through differences in protein synthesis in older adults. The American Journal of Physiology: Endocrinology and Metabolism, 308(1), E21-E28.

[23] Bollwein, J., Diekmann, R., Kaiser, M.J., Bauer, J.M., Uter, W., Sieber, C.C., Volkert, D. (2013) Distribution but not amount of protein intake is associated with frailty: A cross-sectional investigation in the region of Nürnberg. Nutrition Journal, 12(109).

[24] Murphy, C., Phillips, A.M., Oikawa, S.Y. (2016) Dietary protein to maintain muscle mass in aging: A case for per-meal protein recommendation. The Journal of Frailty & Aging, 5(1), 49-58.

[25] Dardevet, D., Rémond, D., Peyron, M-A., Papet, I., Savary-Auzeloux, I., Mosoni, L. (2012) Muscle wasting and resistance of muscle anabolism: The “anabolic threshold concept” for adapted nutritional strategies during sarcopenia. The Scientific World Journal, Article ID 269531.