Time restricted eating...Aligning food timing with circadian rhythms

 If you needed more motivation to start a time restricted eating program...here you go. Another great article from the Institute of Functional Medicine...

Chrononutrition: Food Timing, Circadian Fasting, and Resetting the Body’s Internal Clock

Circadian cycles are part of the body’s internal clock, and disruption to these biological rhythms may result in adverse health outcomes. Aligning meal timing with the body’s circadian cycle for optimal glucose and insulin responsiveness may be effective for improving metabolic health. In the field of chrononutrition, time-restricted feeding has been prominent in research, studied for its benefits on metabolic health and as a means for realigning and supporting the body’s internal clock. How do circadian considerations potentially benefit personalized health interventions for chronic disease treatment or prevention? Timing influences human physiology. Circadian cycles are a property of the body’s internal clock, and disruption to these biological rhythms may result in adverse health outcomes. The field of chronobiology is dynamic and continues to elucidate the associations between circadian rhythms and health implications, from neurodegenerative risks to metabolic dysfunctions.1,2 Chrononutrition is the focused study of the relationship between food, metabolism, meal timing, and the circadian system. Is there metabolic benefit when aligning lifestyle behaviors such as food timing with the body’s internal clock? How do circadian considerations influence personalized health interventions for chronic disease prevention or treatment? Aligning Food Timing With Circadian Rhythms Most cells and tissues of the body show molecular clock activity and express cellular clock genes that contribute to tissue and system function. In metabolic processes, circadian-related components modulate the activation and expression of hormones, enzymes, and signaling pathways.3,4 Aligning meal timing with the body’s circadian cycle for optimal glucose and insulin responsiveness, as well as with hormones such as cortisol and leptin that are also affected by circadian oscillations,3 may be effective for improving metabolic health. A 2023 meta-analysis of nine RCTs (n=485 total participants) compared higher energy consumption earlier in the day with higher consumption later in the day on weight loss and metabolic parameters.5 Researchers reported a significantly greater weight loss in groups with higher energy intakes earlier compared to groups with high energy intake later in the day. In addition, significantly greater reductions in LDL cholesterol, fasting glucose, and insulin resistance (measured by HOMA-IR) were reported in groups with earlier energy intakes compared with later intakes.5 Both glucose tolerance and insulin sensitivity have been shown to be lower in the evening than in the morning,6which may contribute to an increased risk of metabolic dysfunctions for those who habitually eat meals during the evening hours. A 2020 meta-analysis (n=10 acute postprandial studies) investigated whether acute glucose and insulin responses after night-time meals (8 pm–4 am) differed from the responses after day-time meals (7 am–4 pm) in healthy adults.7 Results indicated that after an identical meal, the postprandial glucose and insulin responses were both significantly lower in the day compared to the night.7 Interestingly, specific to carbohydrate intake, a 2022 systematic review of eight randomized clinical trials (n=116 healthy adults) indicated that consumption of carbohydrates at night also led to higher postprandial glycemic values than morning consumption; however, no significant difference between morning and night carbohydrate consumption was found for postprandial insulin values.8 TIME-RESTRICTED FEEDING & CIRCADIAN REALIGNMENT As the field of chrononutrition continues to expand and develop, time-restricted feeding (TRF) has been prominent in research, studied for its benefits on metabolic health and as a means for realigning and supporting the body’s circadian clock.9,10 As a form of circadian fasting, TRF is a dietary pattern that optimizes circadian elements by consuming food and beverage within a shortened window of time during the day, extending a person’s nightly fast to 12 hours or more. A 2022 systematic review of 22 TRF-related randomized controlled trials suggested that among adults with overweight/obesity, TRF may lead to improved insulin resistance and glycemic responsiveness throughout the day.11 Of note, most of the reviewed studies assessed the effects of a 16-hour fast/8-hour feeding regimen (day-time feeding window variable), with only one included study comparing the early TRF (eating between 6 am and 3 pm) with the mid-day TRF (eating between 11 am and 8 pm).11 Synchronizing lifestyle habits such as food timing with circadian biological rhythms has been studied in a range of health areas, including the management of non-alcoholic fatty liver disease,12,13 the reduction of blood pressure,14inflammation,15 reduced cognitive decline,16 and cancer risk.17 Evaluating the feasibility of this therapeutic nutritional approach continues to evolve. A recent pilot study tested the feasibility of implementing TRF in adults with overweight and obesity through a smartphone intervention.18 Fifty participants with a normal eating duration of 14 hours or more were enrolled. After the 90-day TRF trial, the average adherence to logging meal activities and to reducing eating windows was 64% and 47% respectively.18 Of note, 16 of the TRF participants reduced their eating window from an average of 16 hours to approximately 12 hours. In addition, decreases in body weight, waist circumference, and systolic blood pressure were reported.18 Chronotype & Personalized Nutrition It is important to note that some patients may not be suitable candidates for therapeutic fasting treatments due to preexisting conditions. However, for some patients, TRF interventions that optimize circadian elements by encouraging energy intake earlier in the day and increasing the fasting window have the potential to improve metabolic outcomes. As research develops, determining the optimal time period for TRF interventions (early TRF versus mid-day TRF) may be clarified. Ultimately, ideal eating times and habits could be associated with a patient’s chronotype. Genetic variations in clock genes contribute to varied circadian inclinations among individuals and may impact best sleep and meal schedules for any given person. Specific chronotypes, for example, an “early-bird” or “night-owl,” describes not only at what time a person is naturally inclined to sleep and to be awake but may also influence appetite and physical activity.19,20 Studies continue to investigate the impact of chronotype on disease development,21 and chrononutrition trials are beginning to explore chronotype influences on interventions for improved metabolic health.22 As part of a personalized, lifestyle-based approach, nutritional therapies tailored to the individual patient are crucial for effectiveness and sustainability. Circadian rhythms are just one component to consider when creating and implementing dietary interventions. A variety of factors such as potential underlying nutrient deficiencies, presentation of disease symptoms, food sensitivities, accessibility, and personal preferences may all shape personalized treatments. IFM’s suite of therapeutic food plans are all available for modification based on an individual’s health needs. Learn more about food plan personalization within the IFM framework and creating effective and sustainable nutrition-based strategies to promote health through the online course Therapeutic Food Plans: A Component of Personalized Nutrition. Source: <https://www.ifm.org/news-insights/chrononutrition-food-timing-circadian-fasting-and-the-bodys-internal-clock/?utm_campaign=Newsletter&utm_medium=email&_hsmi=251085985&_hsenc=p2ANqtz-8T_k3YJCFivLIRpT-UCW4IK1x8vKKGfijKRnr4-astzNGhHDqTj9WiCepB_vUcJE-ZK70SXU68vmHZtY9rEmT8JsGpZA&utm_content=251085983&utm_source=hs_email> References: 1) Leng Y, Musiek ES, Hu K, Cappuccio FP, Yaffe K. Association between circadian rhythms and neurodegenerative diseases. Lancet Neurol. 2019;18(3):307-318. doi:1016/S1474-4422(18)30461-7 2) Chaput JP, McHill AW, Cox RC, et al. The role of insufficient sleep and circadian misalignment in obesity. Nat Rev Endocrinol. 2023;19(2):82-97. doi:1038/s41574-022-00747-7 3) Serin Y, Acar Tek N. Effect of circadian rhythm on metabolic processes and the regulation of energy balance. Ann Nutr Metab. 2019;74(4):322-330. doi:1159/000500071 4) Flanagan A, Bechtold DA, Pot GK, Johnston JD. Chrono-nutrition: From molecular and neuronal mechanisms to human epidemiology and timed feeding patterns. J Neurochem. 2021;157(1):53-72. doi:1111/jnc.15246 5) Young IE, Poobalan A, Steinbeck K, O’Connor HT, Parker HM. Distribution of energy intake across the day and weight loss: a systematic review and meta-analysis. Obes Rev. 2023;24(3):e13537. doi:1111/obr.13537 6) Mason IC, Qian J, Adler GK, Scheer FAJL. Impact of circadian disruption on glucose metabolism: implications for type 2 diabetes. Diabetologia. 2020;63(3):462-472. doi:1007/s00125-019-05059-6 7) Leung GKW, Huggins CE, Ware RS, Bonham MP. Time of day difference in postprandial glucose and insulin responses: systematic review and meta-analysis of acute postprandial studies. Chronobiol Int. 2020;37(3):311-326. doi:1080/07420528.2019.1683856 8) de Almeida RS, Marot LP, Latorraca COC, Oliveira RÁ, Crispim CA. Is evening carbohydrate intake in healthy individuals associated with higher postprandial glycemia and insulinemia when compared to morning intake? A systematic review and meta-analysis of randomized crossover studies. J Am Nutr Assoc. Published online March 1, 2022. doi:1080/07315724.2022.2043199 9) Adafer R, Messaadi W, Meddahi M, et al. Food timing, circadian rhythm and chrononutrition: a systematic review of time-restricted eating’s effects on human health. Nutrients. 2020;12(12):3770. doi:3390/nu12123770  10) Zeb F, Wu X, Fatima S, et al. Time-restricted feeding regulates molecular mechanisms with involvement of circadian rhythm to prevent metabolic diseases. Nutrition. 2021;89:111244. doi:1016/j.nut.2021.111244  11) Tsitsou S, Zacharodimos N, Poulia KA, Karatzi K, Dimitriadis G, Papakonstantinou E. Effects of time-restricted feeding and Ramadan fasting on body weight, body composition, glucose responses, and insulin resistance: a systematic review of randomized controlled trials. Nutrients. 2022;14(22):4778. doi:3390/nu14224778  12) Perez-Diaz-Del-Campo N, Castelnuovo G, Caviglia GP, Armandi A, Rosso C, Bugianesi E. Role of circadian clock on the pathogenesis and lifestyle management in non-alcoholic fatty liver disease. Nutrients. 2022;14(23):5053. doi:3390/nu14235053 13) Kord-Varkaneh H, Salehi-Sahlabadi A, Tinsley GM, Santos HO, Hekmatdoost A. Effects of time-restricted feeding (16/8) combined with a low-sugar diet on the management of non-alcoholic fatty liver disease: a randomized controlled trial. Nutrition. 2023;105:111847. doi:1016/j.nut.2022.111847  14) Xie Z, He Z, Ye Y, Mao Y. Effects of time-restricted feeding with different feeding windows on metabolic health: a systematic review of human studies. Nutrition. 2022;102:111764. doi:1016/j.nut.2022.111764  15) Ramos-Lopez O, Martinez-Urbistondo D, Vargas-Nuñez JA, Martinez JA. The role of nutrition on meta-inflammation: insights and potential targets in communicable and chronic disease management. Curr Obes Rep. 2022;11(4):305-335. doi:1007/s13679-022-00490-0  16) Currenti W, Godos J, Castellano S, et al. Association between time restricted feeding and cognitive status in older Italian adults. Nutrients. 2021;13(1):191. doi:3390/nu13010191  17) Palomar-Cros A, Espinosa A, Straif K, et al. The association of nighttime fasting duration and prostate cancer risk: results from the Multicase-Control (MCC) study in Spain. Nutrients. 2021;13(8):2662. doi:3390/nu13082662  18)Prasad M, Fine K, Gee A, et al. A smartphone intervention to promote time restricted eating reduces body weight and blood pressure in adults with overweight and obesity: a pilot study. Nutrients. 2021;13(7):2148. doi:3390/nu13072148  19) Beaulieu K, Oustric P, Alkahtani S, et al. Impact of meal timing and chronotype on food reward and appetite control in young adults. Nutrients. 2020;12(5):1506. doi:3390/nu12051506  20) Sempere-Rubio N, Aguas M, Faubel R. Association between chronotype, physical activity and sedentary behaviour: a systematic review. Int J Environ Res Public Health. 2022;19(15):9646. doi:3390/ijerph19159646  21) Barrea L, Vetrani C, Altieri B, et al. The importance of being a ‘lark’ in post-menopausal women with obesity: a ploy to prevent type 2 diabetes mellitus? Nutrients. 2021;13(11):3762. doi:3390/nu13113762  22) Mazri FH, Manaf ZA, Shahar S, Mat Ludin AF, Abdul Basir SM. Development and evaluation of integrated chrono-nutrition weight reduction program among overweight/obese with morning and evening chronotypes. Int J Environ Res Public Health. 2022;19(8):4469. doi:3390/ijerph19084469 Related Articles CHRONOBIOLOGY: THE DYNAMIC FIELD OF RHYTHM AND CLOCK GENES CIRCADIAN FASTING & PRECURSORS TO HEART HEALTH PERSONALIZING NUTRITIONAL INTERVENTIONS

Alternate day fasting and it's metabolic benefits

 

Alternate-Day Fasting in Short Term Safe, Has Metabolic Benefits

Alternate-day fasting (ADF) had positive effects on body weight, cardiovascular measures, and molecular markers of aging when assessed in a randomized controlled trial among healthy adults without obesity or diabetes, researchers report in a study published online August 27, 2019 in Cell Metabolism.

ADF is a different approach to control weight than the common caloric restriction (CR) or intermittent fasting (IF) that restricts daily eating to an 8- to 12-hour window. Although ADF is gaining popularity it has not been subject to randomized clinical trials.

Therefore, Slaven Stekovic, PhD, from the Institute of Molecular Biosciences at the University of Graz in Austria, and colleagues conducted a prospective cohort study with an embedded randomized controlled trial to assess the metabolic effects of ADF. The team initially recruited 30 participants who had followed ADF for at least 6 months before the study began and compared them to 60 healthy controls. Thirty members of the control group were then randomly assigned to ADF for 4 weeks and the other 30 participants ate whatever and whenever they wanted during that time.

Specifically, the 30 people who had followed ADF for 6 months or more and the 30 individuals randomly assigned to ADF alternated between 36 hours of not eating and 12 hours of eating whatever they wanted. These two groups were similar in terms of gender distribution, age, body mass index (BMI), and waist-to-hip ratio at baseline.

Before and after the intervention, participants underwent a battery of anthropometric, physiological, hormonal, metabolic, and biochemical measurements that reflect health status and possible effects of ADF. These included measures of body composition and cardiovascular function, caloric expenditure assessed using food frequency and exercise questionnaires, and bone mineral density at the lumbar spine.

No adverse effects were seen among participants in the ADF group. Their caloric intake dropped from baseline by 37.4% (95% CI, –48.3% to –24.4%), compared with 8.2% (95% CI, –32.2% to 3.6%) in the control group.

BMI among the 4-week fasters fell by 1.2 kg/m2 (95% CI, –1.515 to –0.875; P < .0001). The average reduction in belly fat was 14.5% ± 6.4% (P < .0001).
In addition to changes in body mass and composition, researchers noted metabolic trends, which is why they chose to publish in Cell Metabolism rather than a more general journal. "Cell Metabolism is very open to translational findings and there is probably no other intervention that changes the metabolism of an organism as profoundly as fasting," co-author Frank Madeo, PhD, a professor at the Institute for Molecular Biosciences at the University of Graz in Austria, told Medscape Medical News.

Co-author Harald Sourij, MD, a professor at the Medical University of Graz, summarized the metabolic findings: "Overall a number of changes associated with reduced cardiovascular risk and aging were detected, including reduction in inflammatory markers such as sICAM-1, systolic blood pressure, levels of LDL cholesterol, short-chain fatty acids, and triiodothyronine; increase in polyunsaturated fatty acids; and downregulation of potential pro-aging amino acids, such as methionine.”

The metabolic findings suggest that ADF may be safer than CR, which is more widely practiced.

"CR was previously associated with concerns about bone metabolism or immune cell function. Neither in our short-term randomized, controlled study nor in the 6-months ADF cohort did we observe adverse effects on bone mass, total white blood cell count, or abundance of immune cell subtypes, red blood cell counts, or iron metabolism," Sourij told Medscape Medical News.

He cautions though that longer prospective investigations are needed to monitor these parameters over years to rule out potential adverse effects or development of nutrient deficiencies.

The study didn't compare ADF to IF. "Losing 7 pounds within 4 weeks, as in our study, is a strong weight loss effect that will probably not be achieved by shorter fasting periods. ADF has profound positive effects on body weight, cardiovascular parameters, and molecular markers of aging," Madeo concluded.

The apparent safety of ADF may arise from its mimicking eating patterns of our hunter-and-gatherer forebears, explained Madeo. "Our physiology is familiar with periods of starvation followed by food excesses," he said. For example, starvation sets in motion autophagy, in which cells dismantle and recycle damaged parts, such as organelles and proteins, associated with aging. "Autophagy improves the metabolic functions of cells, and it is switched on after 36 hours of fasting," he said.

The autophagy angle may explain the apparent inferiority of CR. "Low-calorie intake hinders the induction of the age-protective autophagy program, which is switched on during fasting breaks," Madeo continued.

But the researchers caution that we don't yet know the consequences, if any, of strict ADF beyond 6 months, and they suggest a robust comparison of "different fasting regimens with each other and across different cohort types," they write. They also warn that constant bombardment with images of food and easy access to it may hamper attempts at ADF for some individuals, and effects may be ephemeral if the pattern of fasting and eating is abandoned.

The investigators stress the importance of identifying patients who likely cannot thrive on ADF. "Appreciable clinical support and a generally healthy lifestyle should be considered before starting ADF," they write.

That caveat is consistent with a 2017 study by John Trepanowski, PhD, of the department of kinesiology and nutrition at the University of Illinois, Chicago, and colleagues that compared ADF, CR, and no intervention among 100 otherwise healthy obese adults. They found no advantage of ADF over CR for adherence, weight loss, weight maintenance, or cardioprotection.

Yoni Freedhoff, MD, associate professor of family medicine at the University of Ottawa, Ontario, Canada, echoes the cautionary comments.

"ADF is already a clinically relevant intervention if employing it allows a person to lose weight and consequently improve weight-responsive medical conditions, but whether or not it has any long-term risks, or benefits beyond those attributable simply to weight loss, will require long-term study. Of course, as with any intervention for a chronic disease, if the intervention is only temporary and ADF as a lifestyle is abandoned following some health improvements, those improvements are likely only to be temporary as well.”

Limitations of the investigation included enrollment of a small sample of highly motivated individuals who were interested in or already doing ADF.

Sourij has reported receiving unrestricted research grants from AstraZeneca, MSD, and Sanofi-Aventis. The other authors and commentator have reported no relevant financial relationships.

Cell Metab. Published online August 27, 2019.

Neurodegenerative disease and the benefits of a Ketogenic diet..

This is another amazing article by the Institute of Functional Medicine on the neurological benefits of the Ketogenic diet.

<https://www.ifm.org/news-insights/neuro-ketogenic-diet-neurodegenerative-diseases/?utm_campaign=Newsletter&utm_medium=email&_hsmi=245039362&_hsenc=p2ANqtz-8OFVUJFm64w8oLXsNBwWC13kWixc75y6fmv7OzIW694J8o1guI_560SS45-MBc6h8ym503er9ecv9dlL-kBy8SOo2pug&utm_content=245039362&utm_source=hs_email>

Ketogenic diet in Neurodegenerative disease... 

 Ketosis. It has become one of the most popular words of the 21st century. Often connected to weight loss plans, “ketosis” is also strongly associated with epilepsy: the ketogenic diet was first introduced by clinicians as a treatment for epilepsy in the 1920s. Over the last decade, researchers have been studying the effect of ketosis on other neurological and mitochondrial disorders, with promising results.

In ketosis, the mitochondria burn fat instead of glucose for energy metabolism. Ketosis can be achieved through periods of fasting or by restricting the intake of carbohydrates in the diet, leading the body to break down fatty acids to produce higher-than-normal levels of the so-called ketone bodies—acetoacetate, ?-hydroxybutyric acid, and acetone—through a process called ketogenesis, which occurs principally in the mitochondrial matrix in the liver.1 The “state of ketosis” has been shown to exert a protective action against neurological diseases like Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and more.2-4 In AD and PD, human studies have shown a reduction of disease symptoms in participants following a ketogenic diet.5A therapeutic ketogenic diet has been studied by IFM educator Terry Wahls, MD, IFMCP with the specific aim of reversing the symptoms of multiple sclerosis (MS). Such diets have been shown to stimulate mitochondrial biogenesis, improve mitochondrial function, and reduce oxidative stress.2,3,6,7 Dr. Wahls has used ketogenic diets in her clinical practice for a wide variety of health issues that result from mitochondrial disease. In the following IFM video, Dr. Wahls talks about the importance of diet for patients with neurological disease symptoms like fatigue.

(Video Time: 2 minutes) Terry Wahls, MD, is a clinical professor of medicine at the University of Iowa, where she teaches internal medicine residents, sees patients in a therapeutic lifestyle clinic, and conducts clinical trials. Dr. Wahls is a patient with secondary progressive multiple sclerosis. She restored her health using a diet and lifestyle program she designed specifically for her brain. 

Neuroprotection & Ketogenic Therapies

In 2004, the first randomized controlled trial of the ketogenic diet with medium-chain triglycerides in humans with AD or mild cognitive impairment (MCI) showed that higher ketone values were associated with greater improvement in paragraph recall.8 Subsequent studies have demonstrated that ketone bodies act as neuroprotective agents by raising ATP levels and reducing the production of reactive oxygen species in neurological tissues, together with mitochondrial biogenesis, which may help to enhance the regulation of synaptic function.1,6 Caloric restriction, in and of itself, has also been suggested to exert neuroprotective effects, including improved mitochondrial function, decreased oxidative stress and apoptosis, and inhibition of pro-inflammatory mediators such as the cytokines tumor necrosis factor-? and inflammatory interleukins.1

In a 2017 Ketogenic Diet Retention and Feasibility Trial, 15 patients with AD were put on a medium-chain triglyceride–supplemented ketogenic diet: approximately 70% of energy as fat, including the MCT, 20% of energy as protein, and less than 10% of energy as carbohydrates. Researchers observed that in a state of ketosis, the mean score on the Alzheimer’s Disease Assessment Scale cognitive subscale improved significantly during the diet and reverted to baseline after the washout.9

Results from a 2020 systematic review of 10 randomized controlled trials indicated that among adults with MCI and/or AD, adherence to an acute or long-term (45-180 days) ketogenic therapy (ketogenic diet, MCT-based, or ketogenic formulas/meals) improved both acute and long-term cognition.10 Specifically, one of the reviewed studies from 2019 examined the effect of an MCT–based ketogenic diet on the cognitive function of 20 Japanese patients with mild-to-moderate AD.11 At eight weeks, the patients showed significant improvement in their immediate and delayed logical memory tests, and at 12 weeks, they showed significant improvements in a digit-symbol coding test and immediate logical memory test, tests which evaluate verbal memory and cognitive processing speed.11

A study of 150 migraine patients found that the ketogenic diet may be a rapid-onset effective prophylaxis for both episodic and chronic migraine.12 Researchers speculate that the ketogenic diet restores brain excitability and metabolism to counteract neuroinflammation in migraine patients.2 Although the ketogenic diet is seen by many as a promising therapy for diverse neurological diseases, the long-term effects of this kind of diet in humans remains uncertain.2

To this end, some researchers have begun to study the effects of intermittent metabolic switching (IMS).13,14 This entails repeating cycles of a metabolic challenge that induces ketosis (fasting and/or exercise) followed by a recovery period (eating, resting, and sleeping), which may optimize brain function and resilience throughout the lifespan.13This metabolic switching may impact multiple signaling pathways that promote neuroplasticity and resistance of the brain to injury and disease.13 Although IMS may enhance brain function and stress resistance, the research is still new and seen mainly in animal models. The question of what specific IMS regimen(s) is ideal for brain health throughout the life course is also unknown.13

Future research should help us better understand how ketogenic therapies work and what effects they have on mitochondrial function and neurological disorders. Ketogenic diets may prove to be another tool functional medicine clinicians can use to help improve outcomes for patients with neurodegenerative disorders. To learn more, visit IFM’s Bioenergetics Advanced Practice Module (APM).

Related Articles

NEURODEGENERATIVE DISEASE: IMPROVING OUTCOMES THROUGH NUTRITION

EMERGING CONCEPTS: TYPE 2 DIABETES AND THE KETOGENIC DIET

ALZHEIMER’S RISKS, INFLAMMATION, AND LIFESTYLE INTERVENTIONS: AN INTERVIEW BETWEEN NEUROLOGIST DAVID PERLMUTTER, MD, AND IFM EDUCATOR KRISTI HUGHES, ND, IFMCP

FASTING AND MITOCHONDRIAL HEALTH

References

1. Paoli A, Rubini A, Volek JS, Grimaldi KA. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur J Clin Nutr. 2013;67(8):789-796. doi:10.1038/ejcn.2013.116
2. Paoli A, Bianco A, Damiani E, Bosco G. Ketogenic diet in neuromuscular and neurodegenerative diseases. Biomed Res Int. 2014;2014:474296. doi:10.1155/2014/474296
3. Branco AF, Ferreria A, Simões RF, et al. Ketogenic diets: from cancer to mitochondrial diseases and beyond. Eur J Clin Invest. 2016;46(3):285-298. doi:10.1111/eci.12591
4. Pavón S, Lázaro E, Martínez O, et al. Ketogenic diet and cognition in neurological diseases: a systematic review. Nutr Rev. 2021;79(7):802-813. doi:10.1093/nutrit/nuaa113
5. Wlodarek D. Role of ketogenic diets in neurodegenerative diseases (Alzheimer’s disease and Parkinson’s disease). Nutrients. 2019;11(1):E169. doi:10.3390/nu11010169
6. Yang H, Shan W, Zhu F, Wu J, Wang Q. Ketone bodies in neurological diseases: focus on neuroprotection and underlying mechanisms. Front Neurol. 2019;10:585. doi:10.3389/fneur.2019.00585
7. Brocchi A, Rebelos E, Dardano A, Mantuano M, Daniele G. Effects of intermittent fasting on brain metabolism. Nutrients. 2022;14(6):1275. doi:10.3390/nu14061275
8. Reger MA, Henderson ST, Hale C, et al. Effects of beta-hydroxybutyrate on cognition in memory-impaired adults. Neurobiol Aging. 2004;25(3):311-314. doi:10.1016/S0197-4580(03)00087-3
9. Taylor MK, Sullivan DK, Mahnken JD, Burns JM, Swerdlow RH. Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer’s disease. Alzheimer’s Dement. 2017;4:28-36. doi:10.1016/j.trci.2017.11.002
10.  Grammatikopoulou MG, Goulis DG, Gkiouras K, et al. To keto or not to keto? A systematic review of randomized controlled trials assessing the effects of ketogenic therapy on Alzheimer disease. Adv Nutr. 2020;11(6):1583-1602. doi:10.1093/advances/nmaa073
11.  Ota M, Matsuo J, Ishida I, et al. Effects of a medium-chain triglyceride-based ketogenic formula on cognitive function in patients with mild-to-moderate Alzheimer’s disease. Neurosci Lett. 2019;690:232-236. doi:10.1016/j.neulet.2018.10.048
12.  Barbanti P, Fofi L, Aurilia C, Egeo G, Caprio M. Ketogenic diet in migraine: rationale, findings and perspectives. Neurol Sci. 2017;38(Suppl 1):111-115. doi:10.1007/s10072-017-2889-6
13.  Mattson MP, Moehl K, Ghena N, Schmaedick M, Cheng A. Intermittent metabolic switching, neuroplasticity, and brain health. Nat Rev Neurosci. 2018;19(2):63-80. doi:10.1038/nrn.2017.156
14.  Mishra S, Singh B. Intermittent fasting and metabolic switching: a brief overview. Biomed Pharmacol J. 2020;13(3). doi:10.13005/bpj/2030

We consume toxic chemicals without knowing it...

 

Toxic Chemicals We Consume Without Knowing It

Akash Goel, MD

February 23, 2023 <

https://www.medscape.com/viewarticle/988444?ecd=wnl_infocu1_broad_broad_persoexpansion-both_20230311&uac=149193PV&impID=5235753#vp_1>

If the pandemic served as a window into our health, what it revealed was a US population that is not only sick but also seemingly only getting sicker. Life expectancy is falling precipitously. Three fourths of Americans are overweight or obese, half have diabetes or prediabetes, and a majority are metabolically unhealthy. Furthermore, the rates of allergic, inflammatory, and autoimmune diseases are rising at rates of 3%-9% per year in the West, far faster than the speed of genetic change in this population.

Of course, diet and lifestyle are major factors behind such trends, but a grossly underappreciated driver in what ails us is the role of environmental toxins and endocrine-disrupting chemicals. In years past, these factors have largely evaded the traditional Western medical establishment; however, mounting evidence now supports their significance in fertility, metabolic health, and cancer.

Although several industrial chemicals and toxins have been identified as carcinogens and have subsequently been regulated, many more remain persistent in the environment and continue to be freely used. It is therefore incumbent upon both the general public and clinicians to be knowledgeable about these exposures. Here, we review some of the most common exposures and the substantial health risks associated with them, along with some general guidance around best practices for how to minimize exposure.

Microplastics 

"Microplastics" is a term used to describe small fragments or particles of plastic breakdown or microbeads from household or personal care products, measuring less than 5 mm in length.

Plastic waste is accumulating at alarming and devastating proportions — by 2050, it is estimated that by weight, there will be more plastic than fish in the oceans. That translates into hundreds of thousands of tons of microplastics and trillions of these particles in the seas. A recent study demonstrated that microplastics were present in the bloodstream in the majority of 22 otherwise healthy participants.

Since the 1950s, plastic exposure has been shown to promote tumorigenesis in animal studies, and in vitro studies have demonstrated the toxicity of microplastics at the cellular level. However, it is not well known whether the plastic itself is toxic or if it simply serves as a carrier for other environmental toxins to bioaccumulate.

According to Tasha Stoiber, a senior scientist at the Environmental Working Group (EWG), "Microplastics have been widely detected in fish and seafood, as well as other products like bottled water, beer, honey, and tap water." EWG states there are no formal advisories on fish consumption to avoid exposure to microplastics at the moment.

Pressure also is mounting for a ban on microbeads in personal care products.

Until such bans are put in place, it is advised to avoid single-use plastics, favor reusable tote bags for grocery shopping rather than plastic bags, and opt for loose leaf tea or paper tea bags rather than mesh-based alternatives.

Phthalates 

Phthalates are chemicals used to make plastics soft and durable, as well as to bind fragrances. They are commonly found in household items such as vinyl (eg, flooring, shower curtains) and fragrances, air fresheners, and perfumes.

Phthalates are known hormone-disrupting chemicals, exposure to which has been associated with abnormal sexual and brain development in children, as well as lower levels of testosterone in men. Exposures are thought to occur via inhalation, ingestion, and skin contact; however, fasting studies demonstrate that a majority of exposure is probably food related.

To avoid phthalate exposures, recommendations include avoiding polyvinyl chloride plastics (particularly food containers, plastic wrap, and children's toys), which is identifiable by the recycle code number 3, as well as air fresheners and fragranced products.

The EWG's Skin Deep database provides an important resource on phthalate-free personal care products.

Despite pressure from consumer advocacy groups, the US Food and Drug Administration has not yet banned phthalates in food packaging.

Bisphenol A (BPA) 

BPA is a chemical additive used to make clear and hard polycarbonate plastics, as well as epoxy and thermal papers. BPA is one of the highest-volume chemicals, with roughly 6 billion pounds produced each year. BPA is traditionally found in many clear plastic bottles and sippy cups, as well as in the lining of canned foods.

Dioxins and Polychlorinated Biphenyls (PCBs) 

Dioxins are mainly the byproducts of industrial practices; they are released after incineration, trash burning, and fires. PCBs, which are somewhat structurally related to dioxins, were previously found in products such as flame retardants and coolants. Dioxins and PCBs are often grouped in the same category under the umbrella term "persistent organic pollutants" because they break down slowly and remain in the environment even after emissions have been curbed.

Tetrachlorodibenzodioxin, perhaps the best-known dioxin, is a known carcinogen. Dioxins also have been associated with a host of health implications in development, immunity, and reproductive and endocrine systems. Higher levels of PCB exposure have also been associated with an increased risk for mortality from cardiovascular disease.

Notably, dioxin emissions have been reduced by 90% since the 1980s, and the US Environmental Protection Agency (EPA) has banned the use of PCBs in industrial manufacturing since 1979. However, environmental dioxins and PCBs still enter the food chain and accumulate in fat.

The best ways to avoid exposures are through limiting meat, fish, and dairy consumption and trimming the skin and fat from meats. The level of dioxins and PCBs found in meat, eggs, fish, and dairy are approximately 5-10 timeshigher than they are in plant-based foods. Research has shown that farmed salmon is likely to be the most PCB-contaminated protein source in the US diet; however, newer forms of land-based and sustainable aquaculture probably avoid this exposure.

Pesticides 

The growth of modern monoculture agriculture in the United States over the past century has coincided with a dramatic surge in the use of industrial pesticides. In fact, over 90% of the US population have pesticides in their urine and blood, regardless of where they live. Exposures are thought to be food related.

Approximately 1 billion pounds of pesticides are used annually in the United States, including nearly 300 million pounds of glyphosate, which has been identified as a probable carcinogen by European agencies. The EPA has not yet reached this conclusion, although the matter is currently being litigated.

A large European prospective cohort trial demonstrated a lower risk for cancer in those with a greater frequency of self-reported organic food consumption. In addition to cancer risk, relatively elevated blood levels of a pesticide known as beta-hexachlorocyclohexane (B-HCH) are associated with higher all-cause mortality. Also, exposure to DDE — a metabolite of DDT, a chlorinated pesticide heavily used in the 1940s-1960s that still persists in the environment today — has been shown to increase the risk for Alzheimer's-type dementia as well as overall cognitive decline.

Because these chlorinated pesticides are often fat soluble, they seem to accumulate in animal products. Therefore, people consuming a vegetarian diet have been found to have lower levels of B-HCH. This has led to the recommendation that consumers of produce should favor organic over conventional, if possible. Here too, the EWG provides an important resource to consumers in the form of shopper guides regarding pesticides in produce.

Per- and Polyfluoroalkyl Substances (PFAS) 

PFAS are a group of fluorinated compounds discovered in the 1930s. Their chemical composition includes a durable carbon-fluoride bond, giving them a persistence within the environment that has led to their being referred to as "forever chemicals."

PFAS have been detected in the blood of 98% of Americans, and in the rainwater of locations as far afield as Tibet and Antarctica. Even low levels of exposure have been associated with an increased risk for cancer, liver disease, low birthweight, and hormonal disruption.

The properties of PFAS also make them both durable at very high heat and water repellent. Notoriously, the chemical was used by 3M to make Scotchgard for carpets and fabrics and by Dupont to make Teflon for nonstick coating of pots and pans. Although perfluorooctanoic acid (PFOA) was removed from nonstick cookware in 2013, PFAS — a family of thousands of synthetic compounds — remain common in fast-food packaging, water- and stain-repellent clothing, firefighting foam, and personal care products. PFAS are released into the environment during the breakdown of these consumer and industrial products, as well as from dumping from waste facilities.

Alarmingly, the EWG notes that up to 200 million Americans may be exposed to PFAS in their drinking water. In March 2021, the EPA announced that they will be regulating PFAS in drinking water; however, the regulations have not been finalized. Currently, it is up to individual states to test for its presence in the water. The EWG has compiled a map of all known PFAS contamination sites.

To avoid or prevent exposures from PFAS, recommendations include filtering tap water with either reverse osmosis or activated carbon filters, as well as avoiding fast food and carry-out food, if possible, and consumer products labeled as "water resistant," "stain-resistant," and "nonstick."

In a testament to how harmful these chemicals are, the EPA recently revised their lifetime health advisories for PFAS, such as PFOA, to 0.004 parts per trillion, which is more than 10,000 times smaller than the previous limit of 70 parts per trillion. The EPA also has proposed formally designating certain PFAS chemicals as "hazardous substances."

Aging Gracefully

 There is so much discussion around aging and so many people fear it and also look upon it as a negative.

Aging is inevitable and actually a privilege not granted to everyone. I love the following article written in the Daily Om regarding aging gracefully...

Aging Gracefully

As we cultivate our life, our beauty becomes as much about what we are creating and doing as it is about our appearance. We tend to associate youth with beauty, but the truth is that beauty transcends every age. Just as a deciduous tree is stunning in all its stages—from its full leafy green in the summer to its naked skeleton during winter and everything in between—human beings are beautiful throughout their life spans. The early years of our lives tend to be about learning and experiencing as much as we possibly can. We move through the world like sponges, absorbing the ideas of other people and the world. Like a tree in spring, we are waking up to the world. In this youthful phase of life, our physical strength, youth, and beauty help open doors and attract attention. Gradually, we begin to use the information we have gathered to form ideas and opinions of our own. As we cultivate our philosophy about life, our beauty becomes as much about what we are saying, doing, and creating as it is about our appearance. Like a tree in summer, we become full, expressive, beautiful, and productive. When the time comes for us to let go of the creations of our middle lives, we are like a tree in autumn dropping leaves, as we release our past attachments and preparing for a new phase of growth. The children move on, and careers shift or end. The lines on our faces, the stretch marks, and the grey hairs are beautiful testaments to the fullness of our experience. In the winter of our lives, we become stripped down to our essence like a tree. We may become more radiant than ever at this stage, because our inner light shines brighter through our eyes as time passes. Beauty at this age comes from the very core of our being—our essence. This essence is a reminder that there is nothing to fear in growing older and that there is a kind of beauty that comes only after one has spent many years on earth.