Aging and caloric restriction
Ref.: Brandhorst S, Choi IY, Wei M et al. A periodic diet that mimics fasting promotes multi-system regeneration, enhanced cognitive performance, and health span. Cell Metab 2015; 22:86-99
Caloric restriction (CR) is a concept which has shown beneficial effects on health and delaying ageing in different cell and animal models. The main mechanism are reducing a) oxidative damage to proteins, DNA and lipids; b) inflammation; c) dysfunctional proteins and organelles; and d) blood glucose levels, insulin, and IGF-1. In real life chronic CR by up to 40% of daily caloric intake seems not an option for most people. A different way to intervene in nutritional behaviour is intermittent fasting (fasting two day a week or alternate day fasting) and prolonged fasting (PF), where fasting was performed three or more days every two or more weeks.
Brandhorst et al. now published a study where they tested PF first in yeast cells and then in 16 month old mice. In this model they show that beneficial effects expressed – besides other parameters – in lowering blood glucose, insulin, C-reactive protein, IGF-1, white blood cells counts, body weight and increasing autophagy rates and immune system regeneration can be achieved.
In a third step they performed a pilot study in humans to analyse effects of a fasting mimicking diet (FMD). The intervention group consisted of 19 persons (7 females, age 41.8 ± 4.9, 12 males, age 42.5 ± 3.5, range 19.8-67.6 y; ethnicity: Whites 58, Hispanics 18.5, Asian 18.5, Blacks 5 %). The plant-based diet consisted of 1,090 kcal on day 1 (10 % protein, 56 % fat, 34 % carbohydrate) and 725 kcal on day 2-5 (9 % protein, 44 % fat, 47 % carbohydrate) and additional micronutrient supplementation. The study runs for 3 month and include an FMD cycle every 30 days. After 5 days of FMD normal food habits are allowed. Measurements were taken at the end of the first FMD cycle and 5 to 8 days after normal feeding after the last cycle (mean time 75.2 ± 2.7 days in the FMD group, 74.5 ± 6.0 days in the control group).
The measurements revealed a significant decrease in fasting blood glucose and insulin at both time points, while significant elevated serum ketone bodies and IGFBP-1 normalized again. Body weight was reduced significantly at both measurements, while trunk fat showed only a trend to decline. Body weight adjusted lean body mass goes up significantly and bone mineral density, measured in the pelvis, was unchanged. Seven out of 8 persons with elevated CRP in the FMD group showed a normalized CRP while the 11 without prior elevation remained normal. As surrogate marker for regeneration of mesenchymal stem and progenitor cells lin¯cd184+CD45¯ cells are measured which showed an increase without significance and go down again after re-feeding.
I think that this study gives us a deeper insight into the mechanism of dietary interventions and show a potential for stressing the body in that way, that a positive adaptation could be achieved. This seems clear for persons at younger and middle ages and at a (relative) healthy state, but has to be replicated in larger, randomized studies. As we have no knowledge for young old (up to 70/75 y) and old people > 75 y, even those who are frail or have Sarcopenia, those with heart failure or COPD, and even those with multimorbidity (and therefore also polypharmacy), and so on, an FMD intervention maybe associated with adverse effects, including the exacerbation of previous malnutrition and worsening function. The next step should be a carefully designed pilot study with healthy older persons. Such a study may include two other arms: firstly, an arm where strength and endurance training is the only intervention, and secondly an arm, where FMD is a combined with strength and endurance training to show if training alone mimics similar effects or if additional training will be a beneficial add-on.
