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AAPI’S NUTRITION GUIDE TO OPTIMAL HEALTH: USING PRINCIPLES OF FUNCTIONAL MEDICINE AND NUTRITIONAL GENOMICS than the alternate genotype [15]. This is related to high ghrelin levels, which seem to translate to excessive food intake during the evening, lethargy in the morning and lower overall physical activity [16]. A sample of 3311 adolescents from 9 European countries reveals adolescents with short sleep duration (less than 8 hours) have higher body mass index values, body fat, waist and hip circumference and fat mass index. Additionally, these adolescents with short sleep duration are more sedentary and watch more TV. Finally, the group ate less fish, vegetables and fruits. While it is difficult to say which issue comes first in the equation, it is interesting that sleep is also playing a role in the overall biochemical wellbeing of the adolescent community [17]. Gastrointestinal motility is, also, rhythmic with most people having bowel movements in the early morning and rarely at night. Gastrointestinal disruptions are common in shift workers and time zone travelers. In fact, the CLOCK gene is expressed in the cells of the colon [18]. Individuals with certain CLOCK gene variations may be more susceptible to gastrointestinal dysfunction because of changes in sleep cycle. This latest research on sleep calls attention to the importance and opportunity for the holistic practitioner to integrate sleep into the patient/client assessment and treatment plan. It is fundamentally important to understand harmony in the body and its association with nutrition and wellness and the circadian clock; as chronotherapy, an emerging area of personalized practice in which therapy is administered to readjust the circadian clock, becomes a reality. Caloric Restriction Caloric restriction has been shown to delay aging in rodents, extending lifespan by as much as 50%; as well as, enhancing plasticity and 16 resilience when faced with stress, fitting Machteld Huber’s conceptual definition of health [2, 6, 19, 20]. Increased expression of Sirt1 occurs in the presence of caloric restriction and is considered the key controller of the longevity response. Sirt1 is a deacytlase shown to regulate histone modification (an epigenetic effect) and a vast array of physiological functions; including glucose homeostasis, fat metabolism and apoptosis [21, 22]. Nicotinamide adenine dinucleotide (NAD) cofactors play a critical role in regulating CLOCK and Sirt1 gene expression [23]. Sir1 has also been shown to decrease oxidative stress and increase lipolysis; two pathways that may ultimately prolong life [24-26]. While daily caloric restriction is an effective method to decrease body weight in the short term (and potentially promote longevity in the longterm), many people find it difficult to continue to adhere to a daily restriction. Alternate day diet restrictions offer another option for reducing obesity and risk of other chronic diseases. A 75% energy restriction, on alternate days has been shown to be effective in obese adults, offering a new strategy for weight loss that may promote greater compliance long term. A study of 16 obese subjects who completed a 12-week trial of a 2 week control phase, 4 week alternate day modified fasting (ADMF) ‚in-house‛ and a 4 week ADMF, self-selected feeding phase produced an average total of 5.6 +/- 1.0 kg post-treatment; which correlated with expectations in accordance with daily energy restriction. Significant improvement in hunger was seen after two weeks and no compensatory caloric intake was observed on the alternate feed day with participants taking in an average of 95 +/- 6% of calculated energy needs. Significant decreases were also seen in total body fat, LDL cholesterol and systolic blood pressure[27, 28]. The benefits of alternate day diet restrictions do not need to be limited to caloric restriction. In 2012
AAPI’S NUTRITION GUIDE TO OPTIMAL HEALTH: USING PRINCIPLES OF FUNCTIONAL MEDICINE AND NUTRITIONAL GENOMICS fact, animal research has shown alternate dietary composition restriction produces benefits to metabolic health. ApoE*3Leiden mice, considered to be humanized models for atherosclerosis, were used to evaluate and compare the impacts of 4 diet groups: 1) cholesterol free (CON); 2) high cholesterol (HC); 3) an alternate regimen of low cholesterol every other day (ALT); 4) and a daily regimen with cholesterol intake equivalent to the ALT group (MC). The ALT feeding group (low cholesterol diet every other day) experienced most of the beneficial effects of the CON group (cholesterol free daily); including improvements in hepatic and vascular activation and inflammation. Since this study was a cross-over design, cholesterol levels of the ALT group were similar to the HC group during the HC diet, but dropped rapidly after periods of the CON diet, demonstrating an adaptive response to dietary cholesterol intake (i.e., salutogenesis). Atherosclerosis was reduced by 50% in the ALT group; however, serum cholesterol was still lower in the CON group at study end. Serum Amyloid A (SAA) is a liver-derived inflammation marker, and SAA levels in the ALT group were very comparable to the CON group at study end. NFkappaB, the inflammatory transcription factor that controls SAA, showed a 4-fold increase in the HC group. However, the NF-kappaB levels of the ALT group were again comparable to the CON group; whereas the MC group experienced a 3fold increase. These data demonstrate dietary cholesterol has adverse effects on the liver, such as increased inflammation, and alternate cholesterol feeding may reduce or prevent these effects, particularly in the area of inflammation[29]. The obvious next step is to replicate this study in humans to evaluate the realistic effects of these diet strategies. While alternate day diet restrictions produce many benefits and show physiologic adaptability to the positive effects of diet restriction, they are not perfect; but they hold the promise of greater long-term compliance and 17 success with lifestyle change strategies; and another option for a personalized approach to hyperlipidemia prevention and management. Gut Health The microbiome has its own genome to understand, which needs to adapt to our environment, which affects human gastrointestinal health and wellbeing. Three million genes are present in our intestinal microbiome, which is far greater than the 25,000 genes identified in the human genome [30]! Microdiversity seems to equate to resilience and salutogenesis with less microbial diversity seen at old age. An international comparison of microbiomes was conducted across continents and three enterotypes, groups of microbiota that seem to co-occur, were identified. Further research is needed in order to better elucidate associations between these three distinct groups and clinical and biochemical phenotypes of interest. However, researchers now have a way of grouping the microbiome data to understand how these groups may affect diet response and how other environmental factors interact with these groups to form disease susceptibility phenotypes[31]. Ultimately, we will be able to use enteroptype groups in practice to better understand the health trajectory of our patients. There is a complex and interesting symbiotic interplay between food and nutrition, our microbiota, and its genes. We feed our microbes daily with carbohydrates and, in turn, our microbes facilitate our own carbohydrate digestion and keep our gastrointestinal systems functioning properly. In fact, low carbohydrate intake, including fiber, has been shown to be detrimental to the colonic mucosa, decreasing cancer protective metabolites and increasing hazardous metabolite concentrations, further emphasizing the importance of paying attention to gastrointestinoal function in practice[32]. Probiotic supplements and probiotic 2012
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