Recent articles in various journals have highlighted the challenge mere mortals have matching their metabolic needs with the foods they trust and like.
When to eat
In September 2022, a study from the University of Aberdeen, published in the journal Cell Metabolism, caused a stir by potentially dispelling a food timing myth[1]. It looked at the time of day people ate and whether it had any impact on metabolism and weight management. You see, Back in 2013 another study found that calories ingested at different times of the day had different effects on energy utilisation, leading to differential weight loss, even when consumed at iso-caloric amounts[2]. The Aberdeen scientists wanted to know if that was reproducible.
Whilst the numbers of people tested are modest in both trials, the results of the 2022 randomised and cross-over trial indicates that eating at a certain time or not appeared to make no difference to appetite, or weight loss, although they do note a larger breakfast seems to suppress appetite for longer.
Calories
The staple of all contemporary dietician and media determination of a food’s value is typically wrapped in its caloric value. A calorie is the basic unit of measurement for the amount of energy in an item of food. According to the NHS, the average man needs around 2,500 a day, and the average woman around 2,000. So, in theory, 500 calories of cake has the same effect on your weight as 500 of cauliflower?
This concept as all enlightened nutrition professionals know is deeply flawed. In 2021 researchers from the University of Toronto concluded that around 20 per cent of calories in almonds pass right through our bodies confirming that “a calorie labelled may not be a calorie absorbed”[3].
Equally, the caloric notion excludes a key parameter, that of nutrient density and availability – clearly 500 calories of sweetened fizzy beverage is going to have a different nutrient content to the same caloric value of broccoli. Metabolically their ingestion produces radically different outcomes. Energy density and nutrient density are important terms to understand when making food choices. Foods that are energy-dense contain a higher number of calories per serving, while foods that are nutrient-dense contain a higher level of vitamins, minerals, and other important nutrients with little or no added sugars or fats that raise calories and spike blood sugars after ingesting.
Age-related weight changes
It’s quite common to refer to the expanding waistline and related metabolic disruption as middle age spread – at almost any age!. But a group of researchers from Duke University published their findings in the Journal Science in 2021, and it seems that all is not so clear[4]. The scientists analysed the average calories burned by more than 6,600 people ranging from one week old to age 95 as they went about their daily lives in 29 countries worldwide. The data suggest that our metabolisms. whilst faster as a child. do not really start to decline until after age 60. The slowdown is gradual, only 0.7% a year. But a person in their 90s needs 26% fewer calories each day than someone in their 40s, indicating that metabolic changes are only a small part of the reality of adverse shifts in metabolic health as we age.
Metabolism and the Microbiome
In 2019, the largest ongoing scientific nutrition study of its kind, led by an international team of scientists including researchers from King’s College London revealed that individual responses to the same foods are unique, even between identical twins. The results revealed a wide variation in blood responses to the same meals, suggesting that personal differences in metabolism, caused by factors such as the gut microbiome and exercise, are just as important to our health and waistbands as the nutritional composition of our foods.
In 2020 a further paper explored that variability and related personalisation opportunities to utilise the gut microbiome in predicting person-specific physiological responses (such as glycaemic responses) to food[5]. This paper indicated that whilst the earlier one discussed above ruled out circadian variances, the timing of food intake has a predominant effect on downstream metabolic and immune functions in microbiome-dependent and -independent manners.
The peculiar propensity of the gut microbiome to adapt to dietary perturbation is mirrored by the speed at which this adaptation takes place. Dietary constituents may support or impede the growth of particular microbes and also contain foodborne microbes, directly contributing to the net composition of the microbial genetic pool in the gut.
Other dietary elements act as “immunomodulators” and can indirectly affect the microbiome composition in an immune-dependent manner via the regulation of cellular and secreted immune effectors.
Immunity and the gut
The body’s largest collection of immune cells underlies the single-layer epithelium lining the gastrointestinal tract and monitors the luminal contents, which includes trillions of microbes, their products, and substances from the diet[6].
The basal tone of the healthy gut immune system is tolerogenic, despite being exposed to trillions of microbes and their products. While this strong tolerogenic capacity is beneficial to us to avoid inflammatory responses to innocuous dietary and commensal antigens in the healthy state, the inability to dampen this tolerogenic capacity could be detrimental in the setting of enteric infection or sustained inflammation and inappropriately dampening this tolerogenic capacity could underlie the pathogenesis of intestinal inflammatory diseases. The commensal mix of bacteria responds to foods and supplementation of probiotics, where the induction of the Tregs provides appropriate immune management. The use of Akkermansia muciniphila as a component of lifestyle changes confers benefits to the immune system as well as metabolic disruption[7].
Therapeutic Intervention.
Inevitably this intersecting mix of conflicting concepts can leave the individual seeking a strategic approach somewhat confused, but there are a few consistent takeaways – the first is that a diet rich in non-processed foods, plants, fibre and modest protein such as in the traditional Mediterranean diet confers multiple advantages, but it may not be enough.
The microbiome is flexible to exogenous challenges and is also responsive to bacterial stimulants or additions. The role of Akkermansia muciniphila in the generation and management of human health is a fast-emerging area of research with real clinical implications.
Reduction in the abundance of Akkermansia has been implicated in the progression of metabolic, autoimmune, and neurodegenerative diseases[8]. Akkermansia plays a role in the regulation of body weight in both rodents and humans[9]. Furthermore, measures which increase Akkermansia abundance in rodent models of type 2 diabetes result in improved glucose control and insulin resistance[10].
Nutrients and Blood Sugar
Foods consumed that are nutrient-dense supply many of the nutrients the body requires to facilitate a graded response to food ingestion, so reducing the risk of inappropriately raised or lowered blood sugar, a key mechanism of metabolic syndrome which includes insulin resistance, obesity, atherogenic dyslipidaemia and hypertension[11][12].
Various supplemental forms of nutrients are known to improve responses to poor food choices including bioflavonoids, such as resveratrol and quercetin, a group of polyphenol compounds found in plants[13]. Berberine is an alkaloid that is extracted from certain botanical herbs, including barberry, goldenseal, and Oregon grape. In clinical trials, berberine supplementation has been shown to lower lipid levels and improve insulin resistance[14]. A supplemental form of a mineral known as chromium picolinate has also been shown to improve body composition and help manage weight[15].
A more traditional way to ensure adequate nutrient intake and especially fat-soluble nutrients such as A,D,E and K is by eating organ meats –a proprietary approach has been to combine key glandular extracts with essential nutrients to enhance response management when exposed to foods that are calorically dense and nutrient-poor and where the response is typically one of post prandial or reactive hypoglycaemia.
References
[1] Ruddick-Collins LC, Morgan PJ, Fyfe CL, Filipe JAN, Horgan GW, Westerterp KR, Johnston JD, Johnstone AM. Timing of daily calorie loading affects appetite and hunger responses without changes in energy metabolism in healthy subjects with obesity. Cell Metab. 2022 Oct 4;34(10):1472-1485.e6.
[2] Jakubowicz D, Barnea M, Wainstein J, Froy O. High caloric intake at breakfast vs. dinner differentially influences weight loss of overweight and obese women. Obesity (Silver Spring). 2013 Dec;21(12):2504-12.
[3] Nishi SK, Kendall CWC, Bazinet RP, Hanley AJ, Comelli EM, Jenkins DJA, Sievenpiper JL. Almond Bioaccessibility in a Randomized Crossover Trial: Is a Calorie a Calorie? Mayo Clin Proc. 2021 Sep;96(9):2386-2397.
[4] Pontzer H, Yamada Y, Sagayama H, Ainslie PN, Andersen LF, Anderson LJ, Arab L, Baddou I, Bedu-Addo K, Blaak EE, Blanc S, Bonomi AG, Bouten CVC, Bovet P, Buchowski MS, Butte NF, Camps SG, Close GL, Cooper JA, Cooper R, Das SK, Dugas LR, Ekelund U, Entringer S, Forrester T, Fudge BW, Goris AH, Gurven M, Hambly C, El Hamdouchi A, Hoos MB, Hu S, Joonas N, Joosen AM, Katzmarzyk P, Kempen KP, Kimura M, Kraus WE, Kushner RF, Lambert EV, Leonard WR, Lessan N, Martin C, Medin AC, Meijer EP, Morehen JC, Morton JP, Neuhouser ML, Nicklas TA, Ojiambo RM, Pietiläinen KH, Pitsiladis YP, Plange-Rhule J, Plasqui G, Prentice RL, Rabinovich RA, Racette SB, Raichlen DA, Ravussin E, Reynolds RM, Roberts SB, Schuit AJ, Sjödin AM, Stice E, Urlacher SS, Valenti G, Van Etten LM, Van Mil EA, Wells JCK, Wilson G, Wood BM, Yanovski J, Yoshida T, Zhang X, Murphy-Alford AJ, Loechl C, Luke AH, Rood J, Schoeller DA, Westerterp KR, Wong WW, Speakman JR; IAEA DLW Database Consortium. Daily energy expenditure through the human life course. Science. 2021 Aug 13;373(6556):808-812. doi: 10.1126/science.abe5017. PMID: 34385400; PMCID: PMC8370708.
[5] Leshem A, Segal E, Elinav E. The Gut Microbiome and Individual-Specific Responses to Diet. mSystems. 2020 Sep 29;5(5):e00665-20.
[6] Gu BH, Kim M, Yun CH. Regulation of Gastrointestinal Immunity by Metabolites. Nutrients. 2021 Jan 7;13(1):167..
[7] Rodrigues VF, Elias-Oliveira J, Pereira ÍS, Pereira JA, Barbosa SC, Machado MSG, Carlos D. Akkermansia muciniphila and Gut Immune System: A Good Friendship That Attenuates Inflammatory Bowel Disease, Obesity, and Diabetes. Front Immunol. 2022 Jul 7;13:934695
[8] Cheng D, Xie MZ. A review of a potential and promising probiotic candidate-Akkermansia muciniphila. J Appl Microbiol. 2021 Jun;130(6):1813-1822.
[9] Depommier C, Everard A, Druart C, Plovier H, Van Hul M, Vieira-Silva S, Falony G, Raes J, Maiter D, Delzenne NM, de Barsy M, Loumaye A, Hermans MP, Thissen JP, de Vos WM, Cani PD. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med. 2019 Jul;25(7):1096-1103.
[10] Perraudeau, F. et al. Improvements to postprandial glucose control in subjects with type 2 diabetes: a multicenter, double blind, randomized placebo-controlled trial of a novel probiotic formulation. BMJ Open Diabetes Res. Care 8, (2020).
[11] Castro-Barquero S, Ruiz-León AM, Sierra-Pérez M, Estruch R, Casas R. Dietary Strategies for Metabolic Syndrome: A Comprehensive Review. Nutrients. 2020 Sep 29;12(10):2983..
[12] Huang PL. A comprehensive definition for metabolic syndrome. Dis Model Mech. 2009 May-Jun;2(5-6):231-7
[13] Rochlani Y, Pothineni NV, Kovelamudi S, Mehta JL. Metabolic syndrome: pathophysiology, management, and modulation by natural compounds. Ther Adv Cardiovasc Dis. 2017 Aug;11(8):215-225
[14] Cicero AF, Baggioni A. Berberine and Its Role in Chronic Disease. Adv Exp Med Biol. 2016;928:27-45
[15] Willoughby D, Hewlings S, Kalman D. Body Composition Changes in Weight Loss: Strategies and Supplementation for Maintaining Lean Body Mass, a Brief Review. Nutrients. 2018 Dec 3;10(12):1876.
