Julie Albrecht Consultant Dietitian – Nutritionist B.Sc.(Nut). Grad. Dip. Diet. Sports. Nut. A.P.D

The defining characteristics of T2DM, are insulin resistance, persistent hyperglycaemia and the resultant excessive hepatic glucose production, all of which are improved with weight loss. In the management of diabetes, the type of dietary prescription, energy and macronutrient composition is one of continuous debate throughout the world. It is agreed that diets that generate an energy deficit will result in weight loss and the associated improved metabolic profile.

The prescription of intermittent fasting and the resurgence of low carbohydrate, high fat diets, continue to be topics of debate. The World Health Organization (WHO), along with other national authorities have made recommendation to reduce carbohydrate intake, specifically from rapidly
digestible starches and sugars (2). The effectiveness of a dietary intervention, in facilitating weight loss, improving metabolic profile, cardiovascular risk factors, gut health, safety and patient sustainability are key parameters, when considering the prescription of dietary interventions. These are also best supported by lifestyle modifications that embrace increased levels of physical activity.

Research has demonstrated that reducing carbohydrate intake can result in effective weight loss, improvement in glycaemic control, insulin levels and cardiovascular profiles (1,4). Carbohydrate restriction has been show to improve glycaemic control even in the absence of weight loss (1). When reviewing the literature, the definition of LCHF diets differs, though is generally considered to be less than the Australian and American dietary guideline of 45 – 64% of total energy intake, which equates to 230 -310g carbohydrate per day. Moderate carbohydrate intakes range from 26 -45%,
low carbohydrate high fat (LCHF) is considered <26% of total energy – <130g per day, very LCHF diets, (ketogenic), 20 – 50g per day, <10% of total energy intake (2000 Kcal) (1,2,3).

LCHF, is a dietary prescription that is focused on having individuals select unprocessed foods, primarily cruciferous and green leafy vegetables, raw nuts, seeds, eggs, fish, unprocessed animal meats, dairy products and natural plant oils and fats from avocado, coconut and olives (1). The research that is supportive of LCHF highlights the following benefits:
 Controls energy balance through increased satiety and reduced ad libitum energy intake (1)
 Encourages the consumption of nutrient dense foods (1)
 Encourages weight loss (1)
 Improves glycaemic control, plasma TG, HDL-C, ApoB, saturated fat concentrations (1)
 Reduces the number of small dense LDL particles (1).

A randomized control trial conducted by Tay et al, which compared the low carbohydrate and high carbohydrate diet for the management of diabetes, revealed that both LCLSF and HC diets, produced similar weight loss, body composition changes, improvements in CVD risk markers, mood, quality of life and cognitive function (4). However, the LCLSF diet had more favorable effects on lipid profile, glycaemic control, attenuating
glucose fluctuation. Authors have concluded that the incorporation of a low carbohydrate, healthy fat eating plan (50-70g CHO/day) within a comprehensive lifestyle modification program magnifies therapeutic benefits for improving both acute and chronic, glycaemic control, reducing glycaemic variability and enhancing CVD health (4).

Conversely there is a body of literature, which acknowledges that short term effects of LCHF diets (several weeks to < 2 years), though raises the concern that the long term effects, as there is a lack of data on the long term efficacy, safety and health benefits (2). Authors raise concern regarding the impact of a reduced carbohydrate intake on:
 The intake dietary fibre on quality of bowel movements and the production of short- chain fatty acids by the flora of the large intestine (2)
 The impact on mortality (2)
 The adverse effects on cardiovascular parameters including cholesterol, homocysteine and vascular elasticity (2)
 Adverse effect of a high fat exposure on areas of the brain, cognition, memory, mental wellbeing, Alzheimer’s, autistic behaviour, liver damage, cardiometabolic risks, risks of cancer and osteoporosis (2)
 High fat exposure which induces a low intake of fermentable dietary fibres, may lead to changes in intestinal microbiota which are associated with an increased intestinal permeability resulting in endotoxemia and triggers for inflammation and metabolic disorders (2)

An expert panel including those from the WHO, Dutch Health Council, the German food Council, Nordic Dietary Recommendations and the Scientific Advisory Committee on Nutrition in England have concluded that diets rich in fruit, vegetables, cereals, legumes, but also moderate in fat and
calories, combined with sufficient daily activity constitute the best scenario for maintaining a healthy body weight and for the prevention of chronic lifestyle disease (2). These recommendations encompass:
 The moderation of added/free sugar intake (2)
 The selection of wholegrain wheat products over lower fibre starch products (2)
 A fat intake to be less than 40% of energy intake (2)
 A Carbohydrate intake of over 40% of energy intake which corresponds to more than 180g per day (2)

Authors conclude that a general public evidence based recommendation to support Ketogenic Low Carbohydrate High fat diets and LCHF diets as a preventive measure to help reduce risks of type 2 diabetes is premature (2). The role of long term elevated fat consumption with low carbohydrate
warrants further study before general recommendations can be made (2). The above highlights the benefits of a reduced carbohydrate intake, though questions the safety in the longer term.

So, where to from here, when advising what is the most appropriate dietary prescription for the overweight and diabetic patient. The key here is, to identify a dietary prescription which is effective and sustainable for the individual. This in some instances may be the LCHF or, for others, it may be somewhere between the general recommendations and that of the LCHF or that of the Mediterranean diet. What is unequivocal is that the diet should focus on improving nutrient density through the selection of unprocessed foods encompassing a lifestyle that embraces physical activity.

References:
1. Evidence that supports the prescription of low-carbohydrate high-fat diets: a narrative review., Noakes TD, Windt J. Br J Sports Med 2016:51:133 – 139
2. Overweight and diabetes prevention: is a low-carbohydrate –high fat diet recommendable? Bourns F, European Journal of Nutrition (2018) 57:1301 -1312
3. The effect of low- carbohydrate diet on glycaemic control in patients with Type 2 diabetes mellitus. Wang L etal. Nutrients 2018, 10, 661: 1 -13
4. Comparison of low – and high-carbohydrate diets for type 2 diabetes management: a randomized trial. Tay etal. American Journal of Nutrition 2015 Oct; 102(4): 780-90

Julie Albrecht Consultant Dietitian – Nutritionist B.Sc.(Nut). Grad. Dip. Diet. Sports. Nut. A.P.D

Menopause is the natural part of the progression for females through their mid-life journey, generally occurring between the ages of 50 – 51 years with a transition that can last between 4 – 8 years (10).. Menopause symptoms often have a negative impact on the female quality of life (11),
having a significant effect on a females daily personal, professional and social lives (12). The hormonal changes that occur through the menopause transition also influence health and expression of disease.

Throughout the midlife journey there is an observed gain in percentage body fat and weight and a reduction in lean muscle mass (1). In part this is related to chronological age, though also to ovarian age and resultant changes in hormonal profiles. To determine the impact of hormonal change on body composition, researchers explored the changes in weight and body fat after the final menstrual period (FMP), using data from the Study of
Women’s Health Across the Nation (SWANN) to quantify rate of change in body composition and body weight in relation to the date of FMP. They identified that fat and lean mass increase prior to the menopause transition (1). At the start of the menopause transition (MT) the mean rate of fat
mass gain increases from 1% to 1.7% per year leading to a 6% total gain in fat mass over 3.5 -year long MT, which is an absolute gain 1.6 kg. At the onset of MT women begin to lose lean muscle mass at approximately -0.2% during MT, with the total loss averages 0.5%, which represent and mean
absolute decrease of 0.2 kg. These gains and losses continue until 2 years after the final menstrual period (1). The SWANN study participant exhibited an accelerated increase in fat mass and decrease in lean mass, in a 3.6% cumulative rise in proportion fat mass and 1.9% cumulative decline in proportion lean mass over the course of 3.5 year – long MT. There joint rates of change result in no detectable acceleration in weight or BMI at the onset of MT (1). Researchers have concluded that these accelerated gains in fat mass and losses in lean mass are MT related phenomenon (1).

In relation to the changes in body composition that occurs in menopause, there is mounting evidence that MT related variations in both estradiol(E2) and follicle stimulating hormone (FSH) play a plausible role in the regulation of energy balance(1). Estradiol affects energy homeostasis pathways including the CNS control of food intake and energy expenditure, regulation of adipose tissue lipid storage and metabolism and insulin sensitivity (1). There is evidence in rodent and murine experiments that the overarching mechanism for gain in the absence of estrogen is reduction in resting metabolic rate, decline in physical activity and greater caloric intake (1). There is small body of longitudinal observational studies that have found that REE is less in postmenopausal women (1).

As part of the aging process and decline in gonadal function is the potential increased vulnerability to disease in hormone – responsive tissues, including the brain, bone and cardiovascular system (2). This change in hormonal profile leads to vasomotor symptoms, urogenital atrophy, osteopenia, osteoporosis, psychiatric disorders, sexual dysfunction, skin lesions, cardiovascular disease, cancer, metabolic disorders and obesity (2). The most common metabolic disorders include dyslipidaemia, impaired glucose tolerance, insulin resistance, hyperinsulinaemia, type II diabetes and obesity (2).

The dyslipidaemia seen in menopause is often reflected as an increase in low density low protein, and decline in high density lipoprotein and in some cases and increase in triglyceride levels, conferring a potential increased risk of cardiovascular disease (2). The main features of metabolic syndrome in post menopausal women is obesity with associated hyper-insulinaemia and insulin resistance, which is associated with increased oxidative stress, inflammatory and pro-thrombotic processes (2).

Post menopause there is an increase in the presentation of obesity, with women having a greater amount of whole body fat and intra-abdominal fat compared to pre-menopausal women, which largely drives the increased prevalence of metabolic syndrome (2,3). The intra-abdominal adipocytes
produce adipocytokines, such as leptin, adiponectin, resistin, ghrelin, which control energy balance and appetite and influence insulin sensitivity via endocrine mechanisms (2). They also modulate adipocyte size/number and adipogenesis via paracrine mechanisms, playing major role in the
regulation of fat mass (2). Menopausal women have elevated levels of leptin, and resistin and decreased levels of adiponectin and ghrelin (2). High levels of leptin together with low adiponectin show a positive correlation with insulin resistance markers (2).

Adiponectin has anti-obesity, anti-diabetic, anti-cancer and anti- inflammatory properties. It is cardio-protective and linked to lipid metabolism (4, 6). Adiponectin activates AMP-activated kinase and peroxisome proliferator-activated receptor, increasing free fatty acid oxidation, improving
insulin sensitivity, and reducing triglycerides, which may all influence HDL and LDL concentration (4). Adiponectin appears to induce weight loss by stimulating glucose utilization and fatty acid oxidation in peripheral tissues and affect energy expenditure by targeting CNS and increasing oxygen
consumption and thermogenesis (4,5). Adiponectin also decreases insulin resistance (5).

Given the cascade of hormonal and metabolic changes that occur through MT, supporting women to engage in preventative management strategies to minimise their weight gain and optimise lean muscle mass would be advantageous to minimise their presentation of metabolic disorders. Given adiponectin’s role in this presentation, could be a point of management focus. Adopting a healthy lifestyle behaviours which incorporate healthy eating and activity pattern have been shown to improve metabolic parameters. A two year weight loss diet intervention study undertaken by Wenjie Ma, et al, encompassing four different macronutrient profiles, resulted in a significantly increased adiponectin over 2 years (4). The increase in adiponectin was significantly associated with a reduction in waist circumference and LDL and associated with an increase in HDL(4).These improvements in abdominal fat distribution and lipid metabolism occurred independent of weight change (4). Increases in adiponectin were also reported by Vajihe Izadi etal, in overweight and obese people when undertaken healthy dietary pattern with moderate weight loss (6).
The maintenance of regular physical activity is a key component to the maintenance of muscle mass, bone mass, strength, health and wellbeing. Research undertaken by Kriketos et al, has revealed that exercise increases levels of adiponectin and improves insulin sensitivity (7). Women should be supported to adopt lifestyle behaviours that have them be active on most days, accumulating 150 – 300 minutes of moderate intensity activity each week which should encompass two days of strength training activities (9). The mid-life journey through the menopause transition is often a challenging time for many women. It is an opportunity to engage them to focus on self-care and support them in adopting healthy
lifestyles that optimise their health and well-being.

References:
1. Changes in body composition and weight during the menopause transition. Gail A. Greendale, Sheng-Fant Jiang, Arun S. Karlamangla. JCI Insight.
2019;4(5):e124865.https://doi.org/10.1172/jci.insight.124865.
2. Metabolic disorders in menopause. Grzegorz Stachowiak¹, Tomasz Petynski, Magdalena Pertynska-Marczewska. Prz Menopauzalny 2015; 14(1):59-64, JECM June 2016DOI: 10.5114/p,.2015.50000.
3. Effect of menopausal status on lipolysis: Comparison of plasma glycerol levels in middleaged, premenopausal and early post menopausal women., Toth MI, Sites CK, Poehiman ET, Tchemof A., Metabolism 2002
4. Weight-Loss Diets, Adiponectin, and Changes in Cardiometabolic Risk in the 2-Year POUNDS Lost Trial. Wenjie Ma, Tao Huang, Yan Zheng, Molin Wang, George A Bray, Frank M Sacks, and Lu Qi. J Clin Endocrinol Metab. 2016 June; 101(6):2415-2422. Doi: 10.1210/jc.2016-1207.
5. Ghrelin, Leptin, Adiponectin, and Insulin Levels and Concurrent and Future Weight Change in Overweight Postmenopausal Women. Amy C. Soni, MD, Molly B. Conroy, MD, MPH, Rachel H. Mackey, PhD, MPH, and Lewis H. Kuller, MC, Dr PH. Menopause. 2011 March; 18(3): 296-301.
6. Specific dietary patterns and concentrations of adiponectin. Vejihe Izadi and Leila Azadbakht. J Res Med Sci. 2015 Feb; 20(20): 178-184.
7. Exercise Increases Adiponectin Levels and Insulin Sensitivity in Humans. Adamandia D. Kriketos, PHD, Seng Khee Gan, MBBS, FRACP, Ann M. Poynten, MBBS, FRACP, Stuart M. Furler, PHD, Donald J. Chisholm, MBBS, FRACP and Lesley V. Campbell, MBBS, FRACP. Diabetes Care 2004 Feb; 27(2): 629-630. https://doi.org/10.2337/diacare.27.2.629.
8. Effect of diet with or without exercise on abdominal fat in postmenopausal women – a randomised trial. Willemijn A. Van Gemert, Petra H. Peeters, Anne M. May, Adriaan J. H Doornbox, Sjoerd G. Elias, Job Van Der Palen, Wouter Veldhuis, Maaike Stapper, Jantine A. Schuit and Evelyn M. Monninkhof. Gemert et al. BMC Public Health (2019) 19:174. http://doi.org/10.1186/s12889-019-6510-1.
9. Australia’s Physical Activity and Sedentary Behaviour Guidelines and the Australian 24-Hour Movement Guidelines – Australia Government, Department of Health
10. Amanda Griffiths, Sara Jane MacLennan, Juliet Hassard. Menopause and work: An electronic survey of employees’attitudes in the UK. Maturitas 76 (2013) 155-159.
11. Zekiye Karacam, Sibel Erkan Seker. Factors associated with menopausal symptoms and their relationship with the quality of life among Turkish women. Science Direct.
12. Simon FA, Reape NZ. Understanding the menopausal experiences of professional women.Pubmed: 18779760 DOI: 10.1097/gme.0b013e31817b614a.

Sarah Markham BSc (Hons) APD – Consultant Dietitian-Nutritionist

Obesity in women has been linked to number of adverse reproductive outcomes, including delayed time to conception, an increased rate of miscarriage, gestational diabetes, preterm birth and large for gestational age babies, caesarean and instrumental delivery (1). More people are choosing bariatric surgery (BS) as a longterm solution for obesity management and with 80% of bariatric surgery being in women, many of whom are of reproductive age, with pregnancies after BS are becoming far more common (2). A recent systematic review investigating gonadal dysfunction in overweight women found that in 36% of overweight women had PCOS and this resolved in 96% of cases after bariatric intervention (3). Weight loss is documented to have a positive outcome on conception and pregnancy, though weight loss surgery itself and therefore pregnancy after BS is not without risk.

Nutrient deficiencies and electrolyte imbalances are common during the period post BS. Deficiency may be a result of general and procedure specific factors including the type and risk of malabsorption, surgical complications, poor adherence to supplements, food aversion and intolerance, taste disturbance or psychological issues. Pregnancy issues such as nausea and cravings may compound nutritional deficiencies as may the increased nutritional needs for micronutrients such as iron and folate (1).

Given the potential of increased fertility and risk of nutritional deficiencies in this group of women, counselling on contraception, nutrition and the need to plan pregnancy is essential. The literature describes foetal growth restriction (FGR) and Small for gestational age (SGA) infants being twice as likely after BS in comparison with BMI-matched women. This risk is higher with procedures that potentially induce malabsorption such as RYGB (Roux-en-Y Gastric Bypass) when compared with procedures such as AGB (Adjustable Gastric Band) or SG (Sleeve Gastrectomy). It may also be that BS increases the risk for congenital malformations in offspring, but strong epidemiological data are lacking (2). The period after BS is characterized by weight loss which may be rapid after SG and RYGB procedures and slower after AGB. Women are therefore recommended to postpone pregnancy in order to ensure maximal weight loss, weight stabilisation and good nutritional status to support positive clinical outcomes in their pregnancy. A recent review of 14 papers recommended postponing pregnancy until a stable weight is achieved which is typically 12 months after SG or RYGB and 2 years after AGB (2).

The importance of considering good nutrition in this group of women cannot be emphasised enough, as a systematic review identified 27 studies where deficiencies were reported in maternal concentrations of vitamin A, B1, B6, B12, C, D, K, iron, calcium, selenium and phosphorous indicating that vast improvements are required in nutritionally monitoring and care of this group (1). Most studies focus on adherence to micronutrient supplementation, with data available on food intake during pregnancy being scarce. The limited available research suggests that dietary patterns can be improved substantially. It is recommended that pregnant women with a history of BS are given intensive dietetic support, preferably by dietitians who have experience of managing the nutritional complications of bariatric surgery, and that they are closely monitored for nutritional deficiencies (1).

A healthy diet post bariatric surgery differs in food group proportions from that of the non-surgical pregnant population. Greater emphasis is placed on lean protein, fruit and veg and lastly carbohydrate. There is little evidence based specific dietary advice for pregnancy post BS and few published reports on the dietary intakes of this population. Guidelines are therefore based on a combination of post-surgical advice and dietary advice for the pregnancy (2).

Given the risk associated with potential deficiencies in the peri conception period, it is recommended that nutritional supplementation should be optimised preferably 3-6 months prior to conception. The following should be checked every 3 months if planning a pregnancy after BS: serum folate or red cell folate, serum B12 or transcobalamin , serum ferritin, iron studies , full blood count, and serum vitamin A. Additionally every 6 months prothrombin, INR, serum 25-hydroxyvitamin D , calcium, phosphate , magnesium and PTH, serum protein and albumin , renal function and liver tests, serum Vit E , serum zinc, copper and selenium. Vitamin K1 should be monitored if coagulation studies are abnormal (2).

During pregnancy serum levels of many micronutrients and macronutrients will decrease as a result of expanding maternal blood volume and increasing demands of the foetus. The following should be checked each trimester and pregnancy specific ranges used : Serum folate , B12 , ferritin , iron studies including transferrin saturation and FBC , serum vitamin D with calcium, phosphate and magnesium and PTH and serum vitamin A , prothrombin time, INR, serum Vitamin K1, serum protein and albumin , renal function and LFTs. In first trimester vitamin E, zinc, copper and selenium should also be monitored (2).

In their consensus document Shawe et al (2019) noted that there is a lack of evidence on the optimal nutritional monitoring and supplementation in pregnancy after BS. Recommendations were therefore based on the nonpregnant population and supplemented with pregnancy specific data where available. A pregnancy multivitamin will meet most requirements for women considering and during pregnancy post bariatric surgery but additional supplements should be given and doses titrated depending on individual biochemistry. The additional demands of meeting requirements following BS means 1000mcg vitamin B12 will always be required as risk of deficiency is high due to decreased gastric acid and less intrinsic factor (for Bypass and GS procedures). 1200-1500mg calcium is required from both diet and supplements, once again due to reduced gastric acid and absorption (for Bypass and GS procedures). If calcium needs cannot be meet through diet alone, calcium supplements should be in citrated form and it should be taken in divided doses not greater than 600mg/dose to ensure maximal absorption. Calcium should not be taken at the same time as iron supplements as there is competition for absorption. Vitamin D dosages of at least and as high as 6000IU/day, may be needed to achieve target blood levels. In cases of severe Vitamin D deficiency oral doses of up to 50,000IU 1-3 times a week may be required. If Vitamin A levels are low, supplements should be given as Beta-carotene or mixed carotenoids as retinol and retinyl esters have known teratogenicity in high levels (4)(5). Oral supplementation of up to 6000mcg B Carotene per day is recommended and safe until levels normalise (9). If significant vomiting occurs thiamine 300mg daily with B complex or IV thiamine 100mg minimum should be given if oral supplementation not possible (2)(6).

Weight regain following BS is a known problem and it is therefore important to avoid excessive GWG (Gestational Weight Gain) and post-partum weight retention. However insufficient GWG increases the risk of for foetal growth restriction (FGR) and low birth weight (LBW). So far, no specific guidelines for GWG during pregnancy in post bariatric women are available and few studies have focused on the subject (2). Studies have shown that overall women with a history of BS gain less weight during pregnancy compared with women without prior BS especially during the third trimester. Women who conceive within 18 months after surgery also appear to have less GWG in comparison with those who conceive after this period (2). In the case of insufficient or excessive GWG, foetal growth should be closely monitored and diet reviewed. Energy requirements should be individualised on the pre-pregnancy BMI, GWG, and physical activity levels. Beard et al (7) recommend a minimum of 60g protein per day.

All pregnant women are screened for diabetes however, the physiological changes associated with BS mean tolerability (E.g. dumping) and the accuracy of the OGTT should be considered in pregnant women post BS. Women should be managed as per local policy and Hb1c be considered as an alternative to OGTT. Oral glucose tolerance testing (OGTT) is suitable for women with AGB and can be used to screen for diabetes between 24 and 28 weeks.

Breastfeeding in these women should be encouraged for at least 6 months in accordance with general WHO guidelines. Gimenes et al (8) found children born to mothers who had undergone BS and who were breastfed for at least 6 months to have lower fat mass and glucose levels, possibly protecting them from obesity in later life. Some cases of adverse maternal and neo natal outcomes due to micronutrient deficiencies during lactation have been found. It is recommended that women who breast feed after BS have their nutritional status measured closely with additional supplementation prescribed if needed.

Clearly more research is required in the area of pregnancy following BS. It is however clear that this group of women require appropriate nutritional advice and monitoring to ensure positive pregnancy outcomes.

In summary

• Women post BS and of reproductive age women should be given counselling in relation to contraception, pregnancy planning and nutrition.
• Post BS pregnancies are high risk and demand careful management by obstetricians, nutritionists and bariatric surgeons.
• It is recommended to postpone pregnancy after BS until a stable weight is achieved which is typically 12 months after SG or RYGB and 2 years after AGB.
• Supplementation should be started 3-6 months prior to conception and should continue through pregnancy and breast feeding.
• Nutritional biochemistry should be monitored regularly in both the pre and peri pregnancy phase and supplements and diet reviewed according to biochemistry levels
• GWG should be monitored closely and nutritional advice given as needed.
• Techniques for diagnosing gestational diabetes should be tailored to the particular BS that has been performed.
• Guidelines for breastfeeding are in accordance with WHO recommendations and biochemistry monitored and supplements reviewed accordingly.

References

(1) K.Maslin, I.Douek, B. Greenslade and J. Shawe (2019) Nutritional and perinatal outcomes of pregnant women with a history of bariatric surgery: a case series from a UK centre: Journal of Human Nutrition and Dietetics. https://doi.org/10.1111/jhn.12718.

(2) Jill Shawe et al (2019) Pregnancy after Bariatric Surgery: Consensus recommendations for periconception, antenatal and postnatal care, Obesity Reviews.2019;20: 1507-1522.

(3) Jurgen Harreiter et al (2018) Management of Pregnant women after Bariatric Surgey. Journal of Obesity. .org/10.1155/2018/4587064

(4) Endocrine and Nutritional Management of the Post -Bariatric Patient: An Endocrine Society Clinical Practice Guideline. Journal of Clinical Endocrinology and Metabolism, November 2010, 95 (11):4823-4843

(5) Clinical Practice Guideline for The Perioperative Nutritional, Metabolic and Nonsurgical Support of the Bariatric Surgery Patient- 2013 Update: Cosponsored by American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic and Bariatric Surgery: Endocrine Practice Vol19 No2 March/April 2013:337-371

(6) Australian Government Department of Health and Ageing National Health and Medical Research Council : Nutrient Reference values for Australia and New Zealand 2005

(7) Beard JH et al. Reproductive considerations and pregnancy after bariatric surgery: current evidence and recommendations. Obesity Surgery .2008;18(8):1023-1027.

(8) Gimenes et al. Nutritional status of children from women with previous bariatric surgery. Obesity Surgery.2018;28(4):990-995.

(9) WHO.Guideline:Vitamin A supplementation in pregnant women. Geneva, World Health Organisation, 2011.

Julie Albrecht Consultant Dietitian – Nutritionist B.Sc.(Nut). Grad. Dip. Diet. Sports. Nut. A.P.D

Obesity is a life-limiting disease, afflicting 650 million adults world-wide, with predictive models forecasting the prevalence of adult obesity may be as high as 42% by 2030 (2).

Obese individuals have both altered behavioural, metabolic processes and hormone secretions, with altered neuronal mechanisms related to eating behaviour and food and reward processes (5). In reference to behaviour, food reward can be divided into a wanting and a liking component. The liking is the hedonic reaction to pleasure of reward, whereas wanting is the incentive salience linked with the motivation toward a particular item (5). Obese individuals also have an impaired secretion of the incretin hormones, including glucagon-like Peptide (GLP1) (4). During a meal, GLP1 is secreted by intestinal L cells in the duodenum, small bowel and colon and act as a satiety factor and positively influence glucose metabolism (4). Bariatric surgery is currently the most effective way to lose weight, with the highest rates of long term weight loss. The degree of weight loss ranges from 20 – 50% of total body weight, with a greater loss being associated with the mal-absorptive procedures (2).

Bariatric intervention results in altered neuronal responses to food cues, particularly in the reward, gustatory and homeostatic regions, along with the correction of the secretory defect of GLP1 (4,5). A study undertaken by Holsen etal., explored the effects of surgery and the behavioural and neural outcomes at 12 months, which included weight loss, reduction in maladaptive eating, depressed mood, appetite regularity hormones and a reduced desire for palatable food (3).

Further works by Roefs et al., identified that patients who underwent RYGB surgery, have reduced eating pathologies associated with a reduced need for inhibitory processes, higher cognitive control, and increased gustatory activity (5). This indicates that the brain areas involved in the control of temptations to eat are altered in the food reward processes after bariatric surgery. This highlights that the surgery changes in eating behaviour are not only based on a reduction in stomach size, but also on neuronal and psychological processes that relate to eating behaviour (5).

Despite these positive changes, unfortunately, not all patients are able to maintain the weight that they lose. With weight regain, come’s the return of associated metabolic profiles, co-morbidities and the possible behavioural, neuro-hormonal responses and environments that were obstacles to their initial pre-surgery weight loss attempts.

The aetiology associated with weight regain is multifactorial and include pre- operative BMI, nutritional habits, mental health and anatomical changes which result an increased capacity to consume more food volume. In particular, what is commonly seen is that individuals return to the consumption of high fat, high sugar foods and beverages, which are often consumed in a grazing manner, along with a reduced level of physical activity(2).

Obesity is associated with metabolic dysregulation, insulin resistance and possibly neuro-inflammatory changes inducing altered cognitive function (6). Obesity is associated with decreased executive functioning (EF) performance, including attention and set shifting, inhibitory control, abstract reasoning, memory and visuospatial organisation (7). EF is a metacognitive process that allows for the regulation of behaviour towards goal, self –regulation and decision making (7). Recent studies have identified that the short term consumption of high fat +/- high sugar diet triggers neuro-inflammatory processes (6). High fat diets have been demonstrated to impair hippocampus dependent memory function in humans (6). Adults after consuming a high fat diet for five days exhibited significantly reduced focus attention and reduced retrieval speed of information from working and episodic memory, compared with those who consumed a standard diet (6).

Polyphenolic compounds found in colourful fruit and vegetables, particularly berry fruit have potent anti-oxidant and inflammatory activities. An increased intake of fruit and vegetables has been associated with reduced fasting insulin levels (6). Studies in mice have demonstrated that a high fat diet results in an impairment of memory recognition, which was prevented by addition of a blueberry supplement (6).

p>Bariatric surgery results in positive neuro-hormonal changes, which are key determinants in the weight loss journey and outcome. Capitalising on these changes, through establishing lifestyle and eating behaviour patterns that support these is paramount. The adoption of healthy eating behaviours which embrace the consumption of nutrient dense, polyphenol and omega 3 rich foods, limiting the intake of high fat, high sugars foods and beverages is pivotal to long term success.

The establishment and maintenance of new lifestyle behaviours and minimization of behavioural drift is best supported by a multidisciplinary team approach, which acknowledges their success, and addresses the possible psychological, environmental and behavioural factors that may contribute to weight regain.

Teonie Harland, Consultant Dietitian – BHlthSc (Nutr & Diet), APD

Infertility has significant psychological, physical and economic effects on couples (1) with one in six couples experiencing infertility with both male and female factors contributing to these statistics (2). The largest factors affecting fertility in women stems predominantly from anovulation with conditions including polycystic ovary syndrome (PCOS) and diminished ovarian reserve (DOS) (3). Male factors primarily include sperm quality, concentration and motility (4). Evidence supports the significance of nutrition on preconceptions, pregnancy and the first 1000 days (5).
Within both male and female infertility there are replaceable factors such as unhealthy dietary habits, gaining weight and excessive alcohol that negatively affect reproductive health (6).

Obesity plays a significant factor in reproductive disorders . A higher body fat mass in women impacts secretion of gonadotropin due to the increase of aromatisation of androgens to estrogens. The insulin resistance and hyperinsulinemia as a byproduct of obesity leads to hyperandrogenaemia (7). As leptin levels increase, sex hormone binding globulin (SHBG), growth hormone (GH) and insulin like growth factor binding protein (IGFBP) decrease. Leptin inhibits granulosa and thecal cell steroidogenesis directly interfering with ovulation (7). In recent studies with male and female mice,
increasing dietary fat intake resulted in insulin resistance and glucose intolerance however only the female mice developed obesity and hyperleptinemia resulting in a 60% decrease in spontaneous pregnancy rate (7). Weight loss is able to restore infertility in most cases (8).

Male semen quality have been seen to improve with adherence to a healthy diet rich in fish, shellfish, seafood, poultry, cereals, vegetables, fruits, low fat dairy and skimmed milk. However diets rich in a high intake of alcohol, caffeine red and processed meats, full fat dairy, soy foods, potato and sweets are detrimentally associated with the quality and fecundability of semen (4).

A recent female fertility study in mice who consumed a high fat diet identified that the addition of a calcium supplement alleviated reproductive abnormalities (cycle irregularity and subfertility) and resulted in a lower body fat and weight gain (9). When investigating these effects on fertility, it suggested that the estrus cycle was almost restored in the high fat diet fed mice supplemented with calcium. The calcium supplementation was found to restore the follicle stimulating hormone concentration levels to relatively normal. This resulted in a shortened conception time in these mice when compared to high fat fed mice without supplementation and were closely restored to the conception results of the control group (9).
Emerging research investigates the effects of diversity in gut microbiome contributing to obesity development and subsequent insulin resistance. Studies suggest that gut microbiota is significantly altered by high fat diet induced obesity (10). A recent study investigated that the probiotic strains containing Lactobacillus rhamnosus had beneficial effects on body weight, glucose and fat metabolism, insulin sensitivity and chronic systemic inflammation (11). This suggests that the potential for probiotic supplementation to be an additional support in treating obesity related infertility.
When investigating potential lines of treatment, in conjunction with reduced caloric intake and increased physical activity, Saxenda (liraglutide) has proven to significantly lower body weight (6.0%) in overweight and obese patients when compared to placebo. Furthermore, Saxenda reduced fasting glucose and postprandial levels compared to placebo (15). An observational study of 84 overweight or obese women with PCOS treated with liraglutide for 4 weeks had an average weight loss of 9.0kg and a mean BMI decrease of 3.2kg/m2 (16). This research brings the potential for using liraglutide to achieve effective weight loss solutions prior to conception for improved fertility rates.

Complimentary medicines may also play a role; a combination of two herbal medications (Tablet 1 contained Cinnamomum verum, Glycyrrhiza glabra, Hypericum perforatum and Paeonia lactiflora. Tablet 2 contained Tribulus terrestris) in conjunction with diet and physical activity modification resulted in a reduction in oligomenorrhoea (32.9%), Body Mass Index (BMI), Waist Circumference (WC), Fasting Insulin and blood pressure (12). Similarly, research on the effects on inositol found that compared with placebo, it significantly improved ovulation rate and frequency of menstrual cycles (13). The improvement of fertility rates is recurringly related to an improvement in fasting insulin levels in women (14).

Lifestyle modification remains a first line treatment for many infertility conditions. Treatments targeting infertility still center around weight loss as a primary goal, specifically focusing on treatments to reduce fasting insulin levels. Mainstream therapies that concentrate on dietary controlled intake and regular physical activity remain key in optimising fertility however more couples are branching into adjacent therapy lines to compliment the primary treatment. By incorporating a more expanded view of fertility treatment that includes improving microbiome diversity, nutrition herbal supplementation and potential GLP-1 agonists, specifically Saxenda may compliment the weight loss in fertility treatment to achieve a more successful rate of conception. Dietitians guide and support couples to improve their dietary intake, microbiome diversity and metabolic profile to optimise their reproductive health.

References
1. Panth, N., Gavarkovs, A., Tamez, M., & Mattei, J. (2018). The Influence of Diet on Fertility and the Implications for Public Health Nutrition in the United States. Frontiers in public health, 6, 211. doi:10.3389/fpubh.2018.00211
2. Australian Government Department of Health, February 2011. Fertility and Infertility., https://www.health.gov.au/internet/publications/publishing.nsf/Content/womens-health-policy-toc~womens-health-policy-experiences~womens-healthpolicy-experiences-reproductive~womens-health-policy-experiences-reproductive-maternal~womens-health-policy-experiences-reproductivematernal-fert
3. Centre for disease control., Infertility and Public Health, January 2019., https://www.cdc.gov/reproductivehealth/infertility/index.htm
4. Salas-Huetos, A., Bulló, M., & Salas-Salvadó, J. (2017). Dietary patterns, foods and nutrients in male fertility parameters and fecundability: a systematic review of observational studies. Human Reproduction Update, 23(4), 371-389. doi: 10.1093/humupd/dmx006
5. Moore, T., ARefadib, N., Deery, A., Keyes, M., West, S., The First Thousand Days: A Evidence Paper. Centre for Community Child Health. September
2017., https://apo.org.au/system/files/108431/apo-nid108431-436656.pdf
6. Çekici H (2018) Current Nutritional Factors Affecting Fertility and Infertility. Ann Clin Lab Res Vol.6: No.1: 225. doi:10.21767/2386-5180.1000225.
7. Dağ, Z. Ö., & Dilbaz, B. (2015). Impact of obesity on infertility in women. Journal of the Turkish German Gynecological Association, 16(2), 111–117.
doi:10.5152/jtgga.2015.15232
8. Gambineri, A., Laudisio, D., Marocco, C., Radellini, S., Colao, A., & Savastano, S. (2019). Female infertility: which role for obesity?. International
Journal Of Obesity Supplements, 9(1), 65-72. doi: 10.1038/s41367-019-0009-1
9. Zhang, F., Su, H., Song, M., Zheng, J., Liu, F., & Yuan, C. et al. (2019). Calcium Supplementation Alleviates High-Fat Diet-Induced Estrous Cycle
Irregularity and Subfertility Associated with Concomitantly Enhanced Thermogenesis of Brown Adipose Tissue and Browning of White Adipose
Tissue. Journal Of Agricultural And Food Chemistry, 67(25), 7073-7081. doi:
10.1021/acs.jafc.9b0266310.Jiao, N., Baker, S., Nugent, C., Tsompana, M., Cai, L., & Wang, Y. et al. (2018). Gut microbiome may contribute to insulin resistance and systemic inflammation in obese rodents: a meta-analysis. Physiological Genomics, 50(4), 244-254. doi: 10.1152/physiolgenomics.00114.2017
11.Mazloom, K., Siddiqi, I., & Covasa, M. (2019). Probiotics: How Effective Are They in the Fight against Obesity?. Nutrients, 11(2), 258.
doi:10.3390/nu11020258
12.Arentz, S., Smith, C. A., Abbott, J., Fahey, P., Cheema, B. S., & Bensoussan, A. (2017). Combined Lifestyle and Herbal Medicine in Overweight Women with Polycystic Ovary Syndrome (PCOS): A Randomized Controlled Trial. Phytotherapy research : PTR, 31(9), 1330–1340. doi:10.1002/ptr.5858
13.Pundir, J., Psaroudakis, D., Savnur, P., Bhide, P., Sabatini, L., Teede, H., … Thangaratinam, S. (2018). Inositol treatment of anovulation in women with
polycystic ovary syndrome: A meta-analysis of randomised trials. BJOG: An International Journal of Obstetrics and Gynaecology, 125(3), 299-
308. https://doi.org/10.1111/1471-0528.14754
14.Marshall, J. C., & Dunaif, A. (2012). Should all women with PCOS be treated for insulin resistance?. Fertility and sterility, 97(1), 18–22.
doi:10.1016/j.fertnstert.2011.11.036
15.Norvo Nordisk.,Saxenda. (2019) https://www.novonordisk.com.au/content/dam/australia/affiliate/wwwnovonordiskau/Health%20Care%20Professionals/Documents/Saxenda%20pi1%20with%20ARTG%20date.pdf
16.Rasmussen, C. B., & Lindenberg, S. (2014). The effect of liraglutide on weight loss in women with polycystic ovary syndrome: an observational study. Frontiers in endocrinology, 5, 140. doi:10.3389/fendo.2014.00140

Julie Albrecht Consultant Dietitian – Nutritionist B.Sc.(Nut). Grad. Dip. Diet. Sports. Nut. A.P.D

The most recent Global Burden of Disease study continues to place cardiovascular disease (CVD) as the leading cause of death worldwide (1). There continues to be ongoing debate regarding the role dietary fats play in our cardio-metabolic health, along with the role of other dietary components.
In the 1950’s, Ancel Keys, an American scientist, developed a theory which placed dietary saturated fat as the principal promoter of elevated serum cholesterol and heart disease (3). This theory was embraced by the American Heart Association (AHA), who in 1961, recommended that Americans
lower their intake of saturated fat (3). The U.S. federal government also embraced his theory, as it is outlined in the 1977 Dietary Goals (3). Around the same time, John Yudkin, a British physiologist presented a competing theory which argued that sugar was actually more closely related to coronary heart disease (CHD) incidence and mortality (3).

Interestingly, there were observational studies which supported both theories, which is in part because people eat foods, not isolated food constituents (3). When exploring the sources of saturated fat in the diet, they are often also sources of sugar. Often, when one eats a lot of sugar
one also consumes similar amounts of saturated fat. The effect of saturated fat on LDL cholesterol levels and the association of LDL with coronary disease have led to the inference that dietary saturated fat directly promotes the development of coronary heart disease (2).

In decades past the dietary guideline have almost universally advocated reducing the intake of total and saturated fat, replacing saturated fats with polyunsaturated fats and the elimination of trans-fat (2).

In this field of research, some view that the direct evidence on the benefits of lowering cholesterol or LDL cholesterol by changing the fat content of the diet is lacking (2). Meta-analyses and systematic reviews, have placed emphasis on the results of a few trials done 40 – 50 years ago, supplemented by the observations of prospective epidemiological cohort studies (2).

The replacement of saturated fatty acids with polyunsaturated fatty has been part of the US dietary guidelines since the 1970’s. This led to a modest reduction in saturated fat intake and an increase in plant oil consumption, with the intake of polyunsaturated fatty acid increasing from about 3% to 7% of energy intake (2). This was at a time when coronary artery disease mortality fell by close to 75% (2).

This evidence supports the safety of these dietary recommendations, though it difficult to quantify the benefits from changing the type of fats as other dietary and lifestyle factors may also play a pivotal role.

In 2017, the American Heart Association Presidential Advisory strongly endorsed that “lowering saturated fat and replacing it with unsaturated fats, especially polyunsaturated fats, will lower the incidence of CVD” (2). Three months later, the 18 country observational Prospective Rural Urban
Epidemiology (PURE) Study, concluded an opposing view: “Total fat and types of fat were not associated with cardiovascular disease, myocardial infarction, or cardiovascular disease mortality” (2).

When assessing cardiovascular risk, researchers are now investigating the range of LDL particles with different physiochemical characteristics, including size and density (2). These particles and their pathological properties are not accurately measured by the standard LDL cholesterol assay (2). Other atherogenic lipoprotein particles including LDL, intermediate density lipoprotein, very low density lipoprotein and the ratio of serum apolipoprotein B to apolipoprotein A1, have been advocated as alternatives to the assessment and management of cardiovascular disease risk (2).
Blood levels of smaller, cholesterol depleted LDL particles appear to be more strongly associated with cardiovascular risk than the larger cholesterol enriched LDL particle (2). An increased intake of saturated fats can raise plasma LDL levels of the larger LDL particles to a greater extent than the
smaller LDL particle (2). These particles are more susceptible to oxidation, pro-atherogenic, prothrombotic and pro-inflammatory (3). The larger LDL particle may be resistant to oxidation (3). High concentrations of small LDL particles and low concentration of the larger LDL particle has been
associated with greater coronary heart disease (CHD) risk (3). The Quebec Cardiovascular study revealed a three-fold increase in CHD risk in individuals with elevated levels of small-dense LDL, after adjustment for total LDL concentration and other lipid fractions (3). Randomised trial data suggests that eating saturated fat can decrease small dense LDL particles and increase the larger buoyant LDL particle, supporting that the consumption of saturated fats may be favourable with regard to CHD risk (3). Polyunsaturated and monounsaturated fats reduce LDL cholesterol, their effects on cardiovascular disease risk factors that are associated with lipoprotein particles is less clear (2).

In relation to other lipid biomarkers, elevated triglyceride levels and low HDL levels are of continued interest because of their association with insulin resistance and metabolic syndrome (2). Triglyceride level decrease and HDL levels increase when saturated fat, monounsaturated or polyunsaturated fat replace carbohydrate (2). Trans-unsaturated fatty acids are also of interest due to their effect on cardiovascular disease lipid biomarkers, which are associated with cardiovascular disease events (2). Trans fatty acids, such as those in industrially produced hydrogenated oils, when substituted for other macronutrients have been shown to increase levels of LDL cholesterol, and the number of atherogenic particles (LDL, and low density lipoproteins), increasing triglycerides and lowering HDL cholesterol and LDL particle size (2).

Also for consideration is the potential role dietary fatty acid composition may have on cardiovascular disease, specifically through the effects on inflammation, endothelial function, thrombosis, ventricular arrhythmias, and blood pressure, independently of these lipid biomarkers (2).
The intake of dietary carbohydrate should also be considered when exploring the management of our cardio-metabolic health. Researchers have identified that consuming moderate amounts of sugar increase total cholesterol (TC) and triglyceride (TG) (3). Diets high in sugar have been shown to increase TC, TG and LDL and TC / HDL ratio (3). Various metabolic risks, including impaired glucose tolerance, insulin resistance, elevated uric acid levels and altered platelet function have been demonstrated in both human and animal studies, when consuming high sugar diets (3). The effect of
hyperglycaemia, associated with a high sugar diet can lead to glycated LDL, which has been shown to activate platelets and induce vascular inflammation (3). The presence of hyper-insulinaemia may increase CHD risk through a variety of mechanisms; stimulation of smooth muscle cell proliferation, increasing lipogenesis, inducing dyslipidaemia, inflammation, oxidative stress and platelet adhesiveness (3).

The sugars in food are also a heterogeneous group of compounds, with fructose and sucrose -glucose + fructose being of greater concern than glucose or as a polysaccharide in starch (3). Fructose sugars appear to cause a greater derangement, with the elevation of insulin levels, reduced insulin sensitivity, increased fasting glucose concentrations and increased glucose and insulin response to glucose load (3). Fructose, when compared to glucose, increases the oxidation of low density lipoprotein (oxLDL) and the effects of oxLDL on vascular cells causing pathology commonly found in atherosclerosis and CAD (3). These include endothelial cell dysfunction/apoptosis, foam cell formation, abnormal vascular
tone and blood flow, increased cell adhesion molecule expression, pro-clotting and increased intracellular oxidative stress (3). Fructose increases the levels of advanced glycation end products, which may lead to dysfunctional macrophages entering the arterial wall and contribute to atherosclerosis (3). Fructose in the form of sucrose and high fructose corn symptom in processed foods and beverages appears to be potent in producing diet induced leptin resistance (3). Excess fruit or fructose containing sweeteners also increase the risk for non-alcoholic fatty liver disease (NAFLD (3). The
association between CHD and NAFLD is stronger than the link between CHD and smoking, hypertension, male gender, diabetes, high cholesterol or metabolic syndrome (3).

The above is compelling when considering the management of the cardio-metabolic health of our patients. It raises the question of which disease biomarkers we should be monitoring when managing their health. The research highlights that the dietary management of disease risk should
not have a single nutrient focus, though embrace a food matrix. It supports the prescription of a healthy eating lifestyle that embraces nutrient dense whole foods and the minimisation of processed foods and beverages, particularly those high in fats and sugars. This should form the basis of our dietary guidelines.

References
1. Lukas Schwingshackl, Berit Bogensberger, Aleksander Bencic, Sven Knupple, Heiner Boeing, Georg Hoffman., Effects of oils and solid fast on blood lipids: systematic review and network meta-analysis., Journal of Lipid Research., Volume 59, 1771 -1782, 2018.
2. Nita G Forouhi, professor, Ronald M Krauss, professor, Gary Taubes, journalist, Walter Willett, professor. Dietary fat and cardiometabolic health: evidence, controversies and consensus guidance. British Medical Journal, 361: k2139. 2018.
3. James J. DiNicolantionio, PharmD, Sean C. Lucan MD, MPH, MS, James H. O’Keefe, MD, Progress in Cardiovascular Disease58(5): 464 -472; 2016.

The mid-life journey: an opportunity optimise women’s health and well-being.

Julie Albrecht Consultant Dietitian – Nutritionist B.Sc.(Nut). Grad. Dip. Diet. Sports. Nut. A.P.D
Email:julie@foodbodylife.com.au

Menopause is the natural part of the progression for females through their mid-life journey, generally occurring between the ages of 50 – 51 years with a transition that can last between 4 – 8 years (10).. Menopause symptoms often have a negative impact on the female quality of life (11), having a significant effect on a females daily personal, professional and social lives (12). The hormonal changes that occur through the menopause transition also influence health and expression of disease.

Throughout the midlife journey there is an observed gain in percentage body fat and weight and a reduction in lean muscle mass (1). In part this is related to chronological age, though also to ovarian age and resultant changes in hormonal profiles.

To determine the impact of hormonal change on body composition, researchers explored the changes in weight and body fat after the final menstrual period (FMP), using data from the Study of Women’s Health Across the Nation (SWANN) to quantify rate of change in body composition and body weight in relation to the date of FMP. They identified that fat and lean mass increase prior to the menopause transition (1). At the start of the menopause transition (MT) the mean rate of fat mass gain increases from 1% to 1.7% per year leading to a 6% total gain in fat mass over 3.5 yearlong MT, which is an absolute gain 1.6 kg. At the onset of MT women begin to lose lean muscle mass at approximately -0.2% during MT, with the total loss averages 0.5%, which represents a mean absolute decrease of 0.2 kg. These gains and losses continue until 2 years after the final menstrual period (1). The SWANN study participants exhibited an accelerated increase in fat mass and decrease in lean mass, in a 3.6% cumulative rise in proportion fat mass and 1.9% cumulative decline in proportion lean mass over the course of 3.5 year – long MT. Their joint rates of change result in no detectable acceleration in weight or BMI at the onset of MT (1). Researchers have concluded that these accelerated gains in fat mass and losses in lean mass are MT related phenomenon (1).

In relation to the changes in body composition that occurs in menopause, there is mounting evidence that MT related variations in both estradiol(E2) and follicle stimulating hormone (FSH) play a plausible role in the regulation of energy balance(1). Estradiol affects energy homeostasis pathways including the CNS control of food intake and energy expenditure, regulation of adipose tissue lipid storage and metabolism and insulin sensitivity (1). There is evidence in rodent and murine experiments that the overarching mechanism for gain in the absence of estrogen is reduction in resting metabolic rate, decline in physical activity and greater caloric intake (1). There is a small body of longitudinal observational studies that have found that resting energy expenditure (REE) is less in postmenopausal women (1)

A part of the aging process and decline in gonadal function is the potential increased vulnerability to disease in hormone – responsive tissues, including the brain, bone and cardiovascular system (2). This change in hormonal profile leads to vasomotor symptoms, urogenital atrophy, osteopenia, osteoporosis, sexual dysfunction, skin lesions, cardiovascular disease, cancer, metabolic disorders and obesity (2). The most common metabolic disorders include dyslipidaemia, impaired glucose tolerance, insulin resistance, (deleted psychiatric disorders)hyperinsulinaemia, type II diabetes and obesity (2).

The dyslipidaemia seen in menopause is often reflected as an increase in low density low protein, and decline in high density lipoprotein and in some cases an increase in triglyceride levels, conferring a potential increased risk of cardiovascular disease (2)

The main features of metabolic syndrome in post menopausal women is obesity with associated hyper-insulinaemia and insulin resistance, which is associated with increased oxidative stress, inflammatory and pro-thrombotic processes (2).

Post menopause there is an increase in the presentation of obesity, with women having a greater amount of whole body fat and intra-abdominal fat compared to pre-menopausal women, which largely drives the increased prevalence of metabolic syndrome (2,3). The intra-abdominal adipocytes produce adipocytokines, such as leptin, adiponectin, resistin and ghrelin, which control energy balance and appetite and influence insulin sensitivity via endocrine mechanisms (2). They also modulate adipocyte size/number and adipogenesis via paracrine mechanisms, playing a major role in the regulation of fat mass (2). Menopausal women have elevated levels of leptin, and resistin and decreased levels of adiponectin and ghrelin (2). High levels of leptin together with low adiponectin show a positive correlation with insulin resistance markers (2).

Adiponectin has anti-obesity, anti-diabetic, anti-cancer and anti- inflammatory properties. It is cardio-protective and linked to lipid metabolism (4, 6). Adiponectin activates AMP-activated kinase and peroxisome proliferator-activated receptor, increasing free fatty acid oxidation, improving insulin sensitivity, and reducing triglycerides, which may all influence HDL and LDL concentration (4). Adiponectin appears to induce weight loss by stimulating glucose utilization and fatty acid oxidation in peripheral tissues and affect energy expenditure by targeting CNS and increasing oxygen consumption and thermogenesis (4,5). Adiponectin also decreases insulin resistance (5) 

Given the cascade of hormonal and metabolic changes that occur through MT, supporting women to engage in preventative management strategies to minimise their weight gain and optimise lean muscle mass would be advantageous to minimise their presentation of metabolic disorders. Given adiponectin’s role in this presentation, it could be a point of management focus

Adopting healthy lifestyle behaviours which incorporate healthy eating and activity pattern have been shown to improve metabolic parameters. A two year weight loss diet intervention study undertaken by Wenjie Ma, et al, encompassing four different macronutrient profiles, resulted in a significantly increased adiponectin over 2 years (4). The increase in adiponectin was significantly associated with a reduction in waist circumference and LDL
and associated with an increase in HDL(4).These improvements in abdominal fat distribution and lipid metabolism occurred independent of weight change (4). Increases in adiponectin were also reported by Vajihe Izadi etal, in overweight and obese people when undertaking healthy dietary pattern with moderate weight loss (6).

The maintenance of regular physical activity is a key component to the maintenance of muscle mass, bone mass, strength, health and wellbeing. Research undertaken by Kriketos et al, has revealed that exercise increases levels of adiponectin and improves insulin sensitivity (7). Women should be supported to adopt lifestyle behaviours that have them be active on most days, accumulating 150 – 300 minutes of moderate intensity activity each week which should encompass two days of strength training activities (9).

The mid-life journey through the menopause transition is often a challenging time for many women. It is an opportunity to engage them to focus on self-care and support them in adopting healthy lifestyles that optimise their health and well-being.

References:

1. Changes in body composition and weight during the menopause transition. Gail A. Greendale, Sheng-Fant Jiang, Arun S. Karlamangla. JCI Insight. 2019;4(5):e124865.https://doi.org/10.1172/jci.insight.124865.
2. Metabolic disorders in menopause. Grzegorz Stachowiak¹, Tomasz Petynski, Magdalena Pertynska-Marczewska. Prz Menopauzalny 2015; 14(1):59-64, JECM June 2016DOI: 10.5114/p,.2015.50000.
3. Effect of menopausal status on lipolysis: Comparison of plasma glycerol levels in middle-aged, premenopausal and early post menopausal women., Toth MI, Sites CK, Poehiman ET, Tchemof A., Metabolism 2002
4. Weight-Loss Diets, Adiponectin, and Changes in Cardiometabolic Risk in the 2-Year POUNDS Lost Trial. Wenjie Ma, Tao Huang, Yan Zheng, Molin Wang, George A Bray, Frank M Sacks, and Lu Qi. J Clin Endocrinol Metab. 2016 June; 101(6):2415-2422. Doi: 10.1210/jc.2016-1207.
5. Ghrelin, Leptin, Adiponectin, and Insulin Levels and Concurrent and Future Weight Change in Overweight Postmenopausal Women. Amy C. Soni, MD, Molly B. Conroy, MD, MPH, Rachel H. Mackey, PhD, MPH, and Lewis H. Kuller, MC, Dr PH. Menopause. 2011 March; 18(3): 296-301.
6. Specific dietary patterns and concentrations of adiponectin. Vejihe Izadi and Leila Azadbakht. J Res Med Sci. 2015 Feb; 20(20): 178-184.
7. Exercise Increases Adiponectin Levels and Insulin Sensitivity in Humans. Adamandia D. Kriketos, PHD, Seng Khee Gan, MBBS, FRACP, Ann M. Poynten, MBBS, FRACP, Stuart M. Furler, PHD, Donald J. Chisholm, MBBS, FRACP and Lesley V. Campbell, MBBS, FRACP. Diabetes Care 2004 Feb; 27(2): 629-630. https://doi.org/10.2337/diacare.27.2.629.
8. Effect of diet with or without exercise on abdominal fat in postmenopausal women – a randomised trial. Willemijn A. Van Gemert, Petra H. Peeters, Anne M. May, Adriaan J. H Doornbox, Sjoerd G. Elias, Job Van Der Palen, Wouter Veldhuis, Maaike Stapper, Jantine A. Schuit and Evelyn M. Monninkhof. Gemert et al. BMC Public Health (2019) 19:174. http://doi.org/10.1186/s12889-019-6510-1.
9. Australia’s Physical Activity and Sedentary Behaviour Guidelines and the Australian 24-Hour Movement Guidelines – Australia Government, Department of Health 
10. Amanda Griffiths, Sara Jane MacLennan, Juliet Hassard. Menopause and work: An electronic survey of employees’attitudes in the UK. Maturitas 76 (2013) 155-159.
11. Zekiye Karacam, Sibel Erkan Seker. Factors associated with menopausal symptoms and their relationship with the quality of life among Turkish women. Science Direct.
12. Simon FA, Reape NZ. Understanding the menopausal experiences of professional women.Pubmed: 18779760 DOI: 10.1097/gme.0b013e31817b614a

The Neuropsychological Disease Model of Obesity: The Gut- Brain Axis

Julie Albrecht Consultant Dietitian – Nutritionist B.Sc.(Nut). Grad. Dip. Diet. Sports. Nut. A.P.D

Obesity is a worldwide epidemic, with over 650 million adults and 340 million children and adolescents being obese (1).This multifactorial disorder, is the result of the interaction of genetics, host and environment, all which play definitive roles, though none of them satisfactorily explains the aetiology (2). 

Obesity at times has been considered as a consequence of unbalanced feeding conduct, which does not take into account the complexity of its presentation. Recent long term studies reveal a complex scenario which includes neuropsychological and neurobiological factors which involve a different categorization of pathology, proposing that obesity cannot be adequately treated through a simple nutritional plan and associated training and exercise (2). Some researchers are suggesting the adoption of a “behavioural dimension”, developing new approaches that are both preventive and therapeutic, that include obesity within neuropsychological syndromes (2)

There is now increasing evidence which suggests that the microbiome, through different modalities, including interactions through the nervous system, mutual crosstalk with immune and the endocrine systems and the direct synthesis and management of neurochemicals, can impact the hosts’ behaviour (2). The microbiome also plays a crucial role in the gut-brain axis, affecting the bidirectional neurohumoral communication, through the production of neuroactive molecules and regulating the circulating levels of some cytokines (2). The microbiome plays a role in energy homeostasis and it is important to connect the findings relative to metabolic disorders with those concerning neurological and neuropsychological diseases (2). Neurological co-morbidities, such as deficits in memory, learning and executive function, along with anxiety and depression are often seen in the obese individual, with there being some evidence that supports the hypothesis that the brain could be the seat of the initial malfunction leading to obesity (2).

Neurobiological aspects of obesity pathogenesis

The CNS controls, feeding, appetite and energy expenditure, receiving peripheral signals of energy status from gut hormones and adipokines (2). Homeostatic feeding behaviour is regulated by the hypothalamus, whereas the reward related non-homeostatic control of feeding is believed to be influenced by a group of neurons in other neural regions of the brain (2).

The brain regulates the metabolic pathway, where food intake is mainly regulated by the energy needs of the brain based on its ATP disposability (2). The hyperinsulinaemic – hypoglycaemic state, caused by energy deficiency induces the activation of ATP sensitive K channels in the hypothalamus, leading to an increase in hunger feelings, gluconeogenesis stimulation, activation of the stress system and reduction of pancreatic insulin release (2). The energy content of the brain is negatively correlated with BMI, supporting the view point that the brain can regulate body mass by changing food intake and eventually contributing to the obesity pathogenesis (2)

Food intake is also regulated by the reward-related mechanism, through the mesolimbic dopamine (DA) pathways and by stress axis activity. The stress response occurs through the HPA (hypothalamic-pituitary-adrenal) axis activation, ending with cortisol secretion (2). The mesolimbic dopamine release plays a role in perception, with the dysregulation of this process being linked to the development and maintenance of an addiction (2). The unrestricted consumption of tasty hypercaloric food can lead to a state or reward hyposensitivity that is similar to that seen in drug abuse, leading to compulsive like eating behaviours (2). Stress also triggers the release of DA, where people can be susceptible to substances that, via reward processing, motivate individuals to over consume food (2). The consumption of pleasant food further affects reward processing, augmenting the stress-eating cycle (2). The consumption of ‘comfort food’ provides the relief
from the stressful state. There is a hedonic withdrawal that occurs because of the long term exposure to cortisol, then ingrains the reward driven habits (2). The chronically activated dopaminergic reward systems that occur in persistent periods of stress, lead to the development of addiction- like behaviour, where any decrease in dopamine concentration results in the consumption of comfort food, which in the long term can drive weight gain. Chronic stress enhances food intake, a HPA axis hyper-activation that could lead to the evolution of obesity (2).

Obesity and neurological co- morbidities

Clinical studies have identified an association between obesity and neurological disorders, concerning both the central and peripheral nervous system, including cognitive dysfunction, dementia, decline in memory, propensity to risk taking, increase in lower extremity diseases (LED), neuropathy in type I diabetes, peripheral arterial disease (PAD) and asymptomatic neuropathy (2).

Obesity and its neurological co-morbidities are established through an inflammatory state, linked to a high intake of saturated fat, simple sugars, excessive food intake and gut microbiota (GM) dysbiosis (2). The microbiotic dysbiosis contributes to the leaky gut syndrome, allowing the translocation of gut peptides and bacterial products, resulting in the increase in peripheral inflammatory tone, inducing neuro-inflammation (2). The dysfunctional obese tissue leads to an increase in the circulation of inflammatory cytokines, adipokines and FFA. FFA contribute to the development of metabolic syndrome and have a detrimental effect on the CNS and PNS. Neuro-inflammation and lipotoxic FFA impact the CNS, and can lead to dementia, cognitive dysfunction, anxiety and depression and in the PNS lead to peripheral neuropathies (2)

The Microbiota- Gut-Brain Axis

The gut-brain axis is a complex bi-directional system, which allows for the intimate connection between the brain and the gut in which the central and enteric nervous systems communicate, involving the endocrine, immune and neuronal pathways (2). The gut microbiota regulates the communication and function of the axis, with the introduction of the concept of the microbiota-gut-brain (MGB) axis, underlining the pivotal role the GM plays in the development of metabolic and neurological disease (2). The microbiota is a community of microbes, including bacteria, archaea, viruses and fungi that reside in a habitat, establishing with the host a mutually beneficial relationship. The microbiota maintains gut integrity, harvests energy, provides protection against pathogens and regulates the immune system (2). There are more than 1000 bacterial species in the human gastrointestinal tract, which are mainly located in the distal ileum and colon and are dominantly from the Bacteroidetes and Firmicutes phyla (2). The composition of the gut microbiota is dynamic and susceptible to rapid changes in response to external factors, such as diet, stress, smoking, infections or deviation from a healthy state (2). Changes in GM composition and function, namely dybiosis can lead to the development of various diseases and can contribute to the disruption of the molecular dialogue between the gut and brain (2).

The MGB axis is composed of the CNS, Autonomic nervous system (ANS), the neurons of the enteric nervous system (ENS) and the HPA –axis and the GM. Signals from the brain can influence the motor, sensory and secretory modalities of the gastrointestinal tract (GIT), regulate the inflammatory process and influence the GM structure. Visceral messages from the GIT can influence brain function. Under stressful conditions, HPA axis activation results in cortisol release which alters the gut permeability and barrier function, affecting GM composition (2). The gut microbiome can also influence brain function through modulating various brain transmitters, and circulating cytokines that can exceed the blood brain barrier (2).

Microbiome and energy harvest

Research undertaken on the germ free (GF) mouse models provided the first information about the role bacterial flora had in the pathophysiology of obesity. The colonization of GF mice with an obese microbiota induced an increase in total body fat. When eutrophic GF mice received faecal microbiota from obese woman, metabolic complications associated to obesity were observed (2).

Increased energy harvest via colonic fermentation and SCFAs’ production is the most direct process the ”obese –
microbiota” can affect body weight balance, where SCFAs’ can provide up to 10% of total daily caloric intake. SCFAs are an energy substrate for host tissue and also operate as a signalling molecule in the host metabolism (2).

Microbial metabolites can also influence the composition of bile acid species. A reduced amount of bile acid in the intestine has been associated with inflammation and microbiota overgrowth (2). Present evidence suggests that the consumption of fermentable carbohydrate and the supplementation of SCFA results in positive effects on host physiology and energy homeostasis. SCFA’s have different and parallel metabolic processes that affect energy homeostasis, highlighting the need for more studies in order to elucidate the impact of SCFAs (2)

Microbiome and the brain

Several studies suggest that the mutual interplay between the gut microbiome and the CNS via the MGB axis, plays a pivotal role in the occurrence of metabolic disorders, such as diabetes, obesity and also in the development of eating and stress related neuropsychiatric disorders including anxiety and depression (2). The gut microbiota controls eating behaviour by several mechanisms, including changes to taste receptors, regulation of reward pathways, production of toxins that alter mood and deviating neurotransmission by the vagus nerve (2). The vagus nerve plays an important role in the MGB axis as it connects the 100 million neurons of the enteric nervous system to the “nucleus tractus soliatries”. This information is delivered to the hypothalamus, which modulates energy balance, appetite and dietary intake (2). Signals from the commensal micro-organisms are also part of this information, which links the cognitive and emotional nucleus of the CNS with peripheral and gut activity, finally leading to host eating control (2).

The microbiome produces neuroactive metabolites, such as tryptophan, serotonin, gamma-aminobutyric acid GABA, endocannabinoid ligands and ghrelin, which are exact analogs of the mammalian hormones implicated in behaviour and mood signalling (2). The association of microbiota dysbiosis and mood alteration and anxiety has been demonstrated in a few cross-sectional studies, due to an alteration in tryptophan metabolism (2).

The role of microbiome driven inflammation

Immune mediators are important messengers of the complex dialogue that occurs in the gut-brain axis and consequently it mechanistically links the function’s impairments in both the brain and gut, demonstrated by the association between chronic gut inflammation and psychological morbidity (2). In the obese patients, a chronic low grade inflammatory state is maintained, along with peripheral inflammation, the activation of the innate immune components and the loss of intestinal barrier integrity, which can lead to neuro-inflammation (2). Recent studies have demonstrated that dysbiosis and inflammation may concur to the development of various diseases, including obesity and depression disorders (2). It has been clearly confirmed that the gut microbiome can, qualitatively and quantitatively, shape the host immune responses, both in the gut and in systemic tissues (2).

Obesity–associated dysbiosis is characterised by an incredible inflammatory potential microbiota, which activates innate and adaptive immunity in the gut and beyond, increasing inflammatory tone and production of pro-inflammatory cytokines A dysbiotic microbiota (high sugar diet-associated) alters the vagal gut communication, producing an inflammatory state that increases gut permeability (2). Microbiota with enhanced pro-inflammatory activity has been demonstrated to be able to promote intestinal inflammation, including colitis and metabolic syndrome (2).

Gut permeability can be considered the direct consequence of the dysbiotic microbiota-driven local inflammation (2). The leaky gut and the associated inflammation can lead to peripheral insulin resistance and hyperglycaemia, supporting the development of obesity. The increased inflammatory cytokines in the peripheral system can affect the BBB integrity, contributing to the development of mood disorders (2).

The above presents some insight with regard to the complex interplay between the gut, brain, and microbiota and the potential complex role they play in the presentation of obesity, its development and associated co-morbidities.

It raises the importance of encouraging patients to consume diet which reduces intake of saturated fats and simple sugars and is rich in nutrient dense food that support brain and gut health. 

The gut and gluten intolerance
Julie Albrecht Consultant Dietitian – Nutritionist B.Sc.(Nut). Grad. Dip. Diet. Sports. Nut. A.P.D

Non coeliac gluten sensitivity (NCGS), a new syndrome of gluten intolerance, was first reported 30 years ago. The syndrome occurs primarily in adults and was first identified in children in 2012. It is more common in females and young middle aged adults and some thoughts have the incidence higher than coeliac disease and wheat allergy with estimated number 0.63 – 6% of the population. A full appreciation of the prevalence is unknown, generally because of self –diagnosis and management with a gluten free diet (GFD) (1).

The diagnosis of NCGS, is attributed to patients who have an intolerance to gluten, though do not develop antibodies that are typical to coeliac disease (CD), no lesion in the duodenal mucosa nor have a wheat allergy (WA). The commencement of a GFD, results in a complete regression of symptoms (1).

Fifty percent of patients with NCGS have genes encoding – DQ2/DQ8 molecules in their HLA system. The presence of HLA – DQ2 genes is frequently observed in patients with NCGS and those with diarrhoea predominant irritable bowel syndrome (IBS) (1).

Histologically in the patient with NCGS, the gastrointestinal tract and intestinal permeability are normal and histological lesions are minor, with lymphocytic infiltrations in mucosa rated at Marsh 0 or I. Comparatively, in partial or subtotal villous atrophy with crypt hyperplasia, typical of coeliac disease the histological lesions are rated Marsh III and IV. Histologically, mildly inflamed mucosa (Marsh I), is observed more frequently than CD (1).

The pathogenesis of this disorder is poorly recognised, with NCGS mainly demonstrating an upregulation of the primary and no upregulation of the secondary immune response. It has not been determined of what grain ingredients are responsible for the symptoms of the disease. Some studies suggest wheat amylase trypsin inhibitor may play a major role as a trigger of the innate immune response leading to NCGS. It is believed this role can be played by the poorly absorbed fructo-oligosaccaharides and fructans (FODMAP). In all NCGS patients, their IBS like symptoms are significantly improved by reducing their FODMAP intake (1).

The characteristic presentation of the NCGS patient encompasses both gastrointestinal and systemic symptoms, including abdominal pain, nausea, bloating, flatulence and constipation / diarrhoea. Systemic, include headaches, joint and muscle pain, muscle contractions, leg and arm numbness, chronic fatigue, foggy mind, body mass loss, erythema, eczema, anaemia, chronic ulcerative stomatitis and in some instances, difficulties with attention span and depression. In children, symptom expression includes abdominal pain, diarrhoea and  tiredness (1). In patients who present with irritable bowel syndrome (IBS) and respond well to GFD, may have one of the three diseases – WA, CD, NCGS. Some IBS patients can develop NCGS, demonstrating a high
level of Ig A–AGA and gluten sensitive diarrhoea, though with no enteropathy as seen in CD (1).

In reference to diagnosis, it is recommended to exclude CA and WA. There is no laboratory test to assist in the diagnosis, as Ig G antigliadin antibody (AGA) only occurs in 50% of patients with NCGS. Diagnosis is confirmed by provocation test, with symptoms occurring in several hours to days. Objectively, these are vomiting and diarrhoea, and subjectively abdominal pain, nausea, headache and fatigue. A food challenge with wheat should be undertaken after three weeks of maintaining a gluten-free diet (1). Ongoing management encompasses the maintenance of a gluten free diet at a level that prevents the presentation of symptoms.

Reference:

1. Non coeliac sensitivity – A new disease with gluten intolerance., Clinical Nutrition., 34(2015), 189 -194

Consultant Dietitian. BHlthSc (Nutr & Diet), APD. Julie Albrecht and Associates.

Families with children with Autism Spectrum Disorder (ASD) can often struggle with finding direction and guidance to assist in improving their behavioural symptoms. Currently in Australia with 1 in 150 people being diagnosed with ASD more often parents and health professionals question the most effective treatment in improving the severity of these behavioral symptoms to help adjust their children to a ‘normal’ lifestyle (1). These symptoms include; extreme sensitivity to colours and textures particularly to foods, inability to communicate in social settings, constant movements and often an inability to adapt from normal routines or rituals. The current proven treatments for ASD include, psychiatric medications, social therapy, behavioural therapy, nutritional and dietary intervention. However currently there is no mainstream treatment targeting the behavioural and social/communication barriers(2).

Nutritional interventions continue to be an emerging area in improving various neurological conditions. It is currently known that ASD can affect eating patterns, behaviours and even sensory choices which can severely impact the individual’s food variety and volume and hence there macro and micronutrient intake which can severely impact the child’s development and growth. By improving the child’s micronutrient and macronutrient profile we aim to also improve their behavioural severity (2).

There is strong evidence to suggest that vitamin D and omega-3 long chain polyunsaturated fatty acids (PUFAS) assist in reducing the autistic behavioral symptom severity. The active form of vitamin D has been shown to have an important role in the neuronal structure, function, differentiation and connectivity of a developing brain. Therefore, deficiency of vitamin D may be linked to an exacerbation of the symptoms of autism and increased behavioral problems. This has been further emphasised by a study conducted in Italy through the seasons where adults with autism experience enhanced behavioural symptoms within the autumn and winter months and improved expression of behavior within summer. Surprisingly though little attention has been payed to these findings (3).

Furthermore Omega-3 long chain polyunsaturated fatty acids mainly DHA are crucial for the normal development and function of the brain including auditory and visual processing. Research shows that children with ASD have increased omega-6 to omega-3 ratio and low blood concentration of omega-3 PUFAS which could be due to a low dietary intake or a difference in the fatty acid membranes. The research had been limited in this area of application until a more recent double blind, placebo control trial identified that vitamin D and Omega-3 supplementation reduced irritability symptoms with ASD with vitamin D supplementation reducing hyperactivity symptoms in these children (4).

Gluten and casein-free diets have been targeted as a nutritional treatment to assist with ASD behavioral and gastrointestinal symptoms. Anecdotally children with autism have an allergy or high sensitivity to peptides and proteins in foods with gluten and casein. This has shown no statistical significance in improving the verbal or non-verbal communication within the autistic population (5). Despite these findings this dietary modification continues to be followed with many parents and families reporting improvements in behaviour expression. It is essential with these children that despite their higher risk of macro and micronutrient deficiencies that these modifications are followed safely and with the advice of a qualified dietitian.

A promising research avenue involves the gut microbiome, specifically affecting the communication to the brain and an individual’s neurological health (6). Humans with ASD as well as Alzheimer’s and Parkinson’s are known to have increased likelihood of chronic gastrointestinal symptoms including diarrhea, pain, indigestion and constipation as a common co-occurring medical condition suggesting the potential presence of a gut-brain axis (7).

More researchers are investigating the connection with the gut-brain axis through new trials whereby they transfer healthy microbiota via Fecal Microbiota Transplantation (FMT) to individuals lacking certain gut bacteria which was first investigated in Australia. This trial required 8 weeks of active treatment with positive effects being seen up to 2 years following the trial. These trials suggest that increasing the diversification of bacteria (increasing the numbers of Bifodobacterium, Desulfovibrio and Prevotella species) resulted in an average reduction of the Gastrointestinal Symptom Rating Scale by 58% compared to baseline. Considering this link between the gut and brain, improving the microbiome diversity by antibiotics, probiotic, pre-biotics and FMT could be a viable therapy option (8).

With such findings, the application of these within the ASD population will be the largest challenge. To implement vitamin D, omega-3 and Probiotic food or supplement interventions, the key factors that need to be considered within the population is not what to take, it is how to take them (3) (4) (8). The role of a dietitian is to assess the behavioral and food aversions that will influence the child’s ability to trial new foods and supplements and work with the child and their families to counsel, guide and persist in small steps to achieve the ultimate goal; to improve ASD behvioural symptoms in children.

My approach to guiding children and their families initially begins with building a range of foods across various colours and textures using the SOS approach to feeding which focuses on the six major steps to eating. I delve into the multiple senses and feeding therapy to introduce tolerance and variety with new foods. In combination with managing food sensitivity/selectivity I also work on solving gastrointestinal issues and managing weight and deficiencies to progress children to having a healthier, happier relationship with food.

References
1. Australian Government, Australian Institue of Health and Welfare. (2015). Autism in Australia. https://www.aihw.gov.au/reports/disability/autism-inaustralia/contents/autism
2. Arnold, G., Hyman, S., Mooney, R., & Kirby, R. (2003). Plasma Amino Acids Profiles in Children with Autism: Potential Risk of Nutritional Deficiencies. Journal Of Autism And Developmental Disorders, 33(4), 449-
454. https://doi.org/10.1023/a:1025071014191
3. Sathe, N., Andrews, J., McPheeters, M., & Warren, Z. (2017). Nutritional and Dietary Interventions for Autism Spectrum Disorder: A Systematic Review. Pediatrics, 139(6). https://doi.org/10.1542/peds.2017-0346
4. Mazahery, H., Conlon, C., Beck, K., Kruger, M., Stonehouse, W., & Camargo, C. et al. (2016). Vitamin D and omega-3 fatty acid supplements in children with autism spectrum disorder: a study protocol for a factorial randomised, double-blind, placebo-controlled trial. Trials, 17(1). https://doi.org/10.1186/s13063-016-1428-8
5. Elder, J., Shankar, M., Shuster, J., Theriaque, D., Burns, S., & Sherrill, L. (2007). The Gluten-Free, Casein-Free Diet In Autism: Results of A Preliminary Double Blind Clinical Trial. Journal Of Medical Speech-Language
Pathology, 15(4), 337-345. https://doi.org/10.1007/s10803-006-0079-0 
6. Ersoz Alan, B., & Gulerman, F. (2019). The Role of Gut Microbiota in Autism Spectrum Disorder. Turkish Journal Of Psychiatry. https://doi.org/10.5080/u23560
7. Xu, M., Xu, X., Li, J., & Li, F. (2019). Association Between Gut Microbiota and Autism Spectrum Disorder: A Systematic Review and MetaAnalysis. Frontiers In Psychiatry, 10. https://doi.org/10.3389/fpsyt.2019.00473
8. Kang, D., Adams, J., Coleman, D., Pollard, E., Maldonado, J., & McDonoughMeans, S. et al. (2019). Long-term benefit of Microbiota Transfer Therapy on autism symptoms and gut microbiota. Scientific
Reports, 9(1).https://doi.org/10.1038/s41598-019-42183-0

Gastrointestinal disorder – The role of the mast cells

Julie Albrecht Consultant Dietitian – Nutritionist B.Sc.(Nut). Grad. Dip. Diet. Sports. Nut. A.P.D Email:julie@foodbodylife.com.au

Mast cells have been identified as a major player in gastrointestinal disorders (2). Mast cells are a multifunction immune cell, and have a crucial role in both innate and adaptive immunity, participating in host defence, tissue repair, wound healing and angiogenesis (2). They play an important immuno-regulatory function, particularly at the mucosal barrier between the body and the environment (1).

The gastrointestinal tract and its intestinal mucosa, have a large interface with the inner and outer environments, constantly exposed to luminal contents (1, 4). The function of this intestinal barrier is to protect the body from harmful luminal content and control mucosal permeability, only allowing small amounts of antigens and bacteria to cross the epithelium, while preventing the passage of potentially harmful substances (4).

The maintenance of the intestinal barrier is fundamental for homeostasis and disturbance of this barrier by an uncontrolled mechanism may lead to enhanced mucosal permeability and passage of luminal antigens and or microorganisms across the intestinal epithelium, potentially inducing disturbances in the epithelial – neuro-hormone interactions that facilitate the development of inflammation in the gut (4). Impaired epithelial barrier function has been largely implicated in the origin and development of many digestive and non-digestive diseases (4).

A variety of research methodologies have identified an increased number of MC in the intestinal mucosa of patients with altered barrier function, in inflammatory intestinal diseases and functional gastrointestinal disorders (4).

MC are long-lived granulated immune cells, that reside in all vascularised tissue in the body, and preferably reside in mucosal interfaces, including the skin, respiratory, genito-urinary and gut mucosa, hence are in close contact with the environment, with the potential to react against infectious organisms, harmful substances and other environmental challenges (4).

Mast cells (MC) have a great variety of receptors and respond to different stimuli including microbial, neural, immune, hormonal, metabolic and chemical triggers, thereby exerting antimicrobial, neurological, immune and metabolic functions (4). In the intestinal mucosa, mediators released by MC affect epithelial integrity and viability, blood flow, coagulation, and vascular permeability, wound healing and fibrosis and facilitate neuro-immune , which promote peristalsis and pain perception (4).

MC have the ability to react to a great variety of stimuli and secrete biologically active products with pro-inflammatory, anti-inflammatory and or immunosuppressive properties (4). They play a prominent role in IgE mediated allergic inflammation and in a variety of intestinal and non-intestinal disease including gastrointestinal inflammation, functional gut disorders, infections, auto-immune disease, atherosclerosis and carcinogenesis (4).

MC play a fundamental role in the regulation of mucosal integrity and epithelial barrier activity and the maintenance of neuro-immuno interaction which support the gut brain axis (4).

MC can be activated by a variety of different mechanisms, including IgE and non-Ig E mediated and Ig G triggers, microbial agents and endogenous factors from cell damage and endogenous stimuli, including neurotransmitters, neuropeptides, neurotrophins and gaseous neurotransmitters (3,4).

MC, when activated release biologically active products including proteases, biogenic amines, proteoglycans, lysosomal enzymes, certain cytokines, growth factors and granule membrane associated proteins (4).

Piecemeal and anaphylactic degradation are the two main mechanisms of secretion of mast cell mediators (4). Digestive diseases involving piecemeal degradation, including inflammatory bowel disease, irritable bowel syndrome and functional dyspepsia, have been the most studied (4).

The intestinal barrier functions as an effective defensive system involving intra –and extracellular elements which closely interact to promote the correct functioning of the epithelium, immune response and acquisition of tolerance against food antigens and the intestinal microbiota (4). The loss of epithelial integrity facilitates penetration into the mucosa, triggering immunological responses, increasing epithelial permeability and promoting inflammation (4).

Abnormality of the intestinal barrier has been identified in the origins and development of many digestive (coeliac disease, IBD, IBS and food allergy) and non-digestive diseases (schizophrenia, diabetes, sepsis and others) (4).

A network of interactions among the microbiota, epithelial cells and immune and nervous system control the intestinal barrier (4). The bilateral communication between the central and enteric nervous systems, regulates ion secretion, epithelial tightness, immune function and peristalsis and hence regulation of the intestinal barrier (4).

MC, contribute to barrier function through a neuro-immune mechanism which has been evidenced in different experimental settings (4). Stressors, both physical and psychological, acute and chronic have been shown to increase ion secretion and epithelial permeability, resulting in a disturbance of barrier homeostasis, with these effects being avoided in “mast cell knock out” rats and in humans treated with a mast cell stabilizing agent (4).

Epithelial function and integrity is regulated by a variety of molecules released by the MC, including tryptase, chymase, histamine and cytokines (4). Tryptase is an enzyme contained in the mast cell and has been largely implicated in epithelial permeability, promoting tight junction disruption, increasing intestinal permeability and cell damage (4). Chymase is mainly implicated in extracellular degradation impacting epithelial integrity (4). Histamine is a mast cell mediator in the gastrointestinal tract, mediating immunological responses, visceral nociception, modulation of intestinal motility, gastric acid secretion through activation of it receptor H1-H4 (4). Histamine’s role in epithelial dysfunction is mediated by H1 receptors, directly stimulating chloride secretion (4). A large variety of cytokines are produced by MC, many of which have a direct impact on the intestinal epithelial barrier, which can result in the disruption of the tight junction, modulation of epithelial paracellular permeability , regulation of intestinal function and increasing intestinal permeability associated with genetic profile identified in intestinal anaphylaxis leading to tight junction disruption (4). Cytokine IL20 has been shown to have anti-inflammatory effects developing a protective role in the intestinal barrier function (4).

MC, are involved in gastrointestinal and systemic manifestation of food allergy (4). MC are the main effector participant in allergic response involving the gastrointestinal tract, where the immune response can be IgE mediated, non IgE mediated or mixed (4). MC activation increases intestinal permeability, along with contribution to the initiation of food allergic inflammation (4). MC have a pro-inflammatory role and modulate the allergic sensitization and downregulation of allergic inflammation (4).

Human and experimental studies have identified the role of MC in IBD, where increased numbers of MC were identified in tissue specimens in Ulcerative Colitis and Crohn’s Disease patients (4). Altered gut-brain axis and a potential role in neural inflammation have also been identified in IBD patients (4).

A chronic inflammatory disorder of the small intestine, Coeliac disease, caused by an intolerance to gluten, has an identifiable increased number of MC and the mediator histamine in the small intestine (4).

In the functional gut disorder, IBS, research to date, has not been able to identify a biomarker. However, low grade inflammatory infiltrate, with an increased number of MC and T –lymphocytes have been identified in the mucosa of the small and large intestine (4). Studies have identified common findings including altered intestinal barrier with increased epithelial permeability and disruption of tight junction (4). The associated loss of functional integrity may facilitate the flux of antigens, including from food, microorganisms and toxins, resulting in stimulation of immunological responses, further increasing the paracellular epithelial permeability and promoting low – grade inflammation (4). In the small intestine of IBS – diarrhoea patients, tryptase has been implicated in intestinal barrier deregulation, gastrointestinal motor abnormalities and visceral pain (4). In the IBS
patient, there is a correlation between the severity of pain and the number of colonic mast cells in proximity to nerves (4). MC support a local neuro-immune interaction between the brain and the gut, mediating the response to psychological stress, with recent research identifying the relationship between stress episodes and the initiation / exacerbation of functional gut disorders (4). This relationship has been support by studies identifying an improvement in gastrointestinal symptoms after the administration of the mast cell stabilizer disodium chromoglycate or ketotifen, H1 receptor antagonist, leading to a reduced visceral perception, particularly in hypersensitive IBS patients (4).

Functional dyspepsia, is one of the most common functional gut disorders, with a prevalence of 10 – 20%, characterised by symptoms including epigastric pain, sensation of fullness, nausea, early subjective satiety and abdominal bloating (4). Studies have identified and increased number of MC and eosinophils in the duodenum, though no biomarker has been identified (4). The identified higher number of mast cells with an activated phenotype does not appear to correlate with the impaired mucosal barrier integrity observed in the duodenal mucosa, though evidence still suggest MC activation may play a role (4).

Mast Cell Activation Syndrome (MCAS) is a chronic multisystem disease of abnormal MC activation, leading to inflammatory and allergic symptoms (2). The most common symptoms include abdominal pain, nausea both, cyclical and chronic, vomiting, heart burn, alternating diarrhoea and constipation (2, 4). Other symptoms may include, tingling and burning, apthous ulcers, globus, abdominal bloating, and dysphagia (2). In these individual symptoms are often refractory to targeted medications (2).

MCAS involves a constitutive and reactive abnormal activation and release of mediators which have harmful effects locally and distantly (2). CD-117 immuno-histochemical staining is used to detect MC within the GI tract mucosa obtained via endoscopic biopsy, with the general protocol to obtain 8 specimens from the second part of the duodenum (2). In most MCAS patients, researchers have identified ≥20 MC per hpf from the duodenum and ileum (2).

Mast cells play a major role in the maintenance of intestinal barrier and the neuro-immune interaction which supports the gut –brain axis. Studies have identified the role of MC in IBD, IBS and functional dyspepsia and MCAS.

Emerging research has identified treatment which encompasses the identification and avoidance of MC triggers and the control of mast cell mediator production and action. First line management encompasses the avoidance of potential triggers which may include stress, heat and alcohol (2). Researched clinical experience also identified dietary interventions, encompassing the avoidance of gluten, dairy protein, histamines and moderating FODMAP load as part of first line management (2).

First line pharmacotherapy is offered in a stepwise fashion, introducing one medication at a time to determine the benefit (2). This initial intervention could encompass the use of histamine receptor antagonists, which block receptors on MC and other cells throughout the body which are responsible for symptoms (2). These medications could include non- sedating H1 – receptor antagonists, Ceterizine and Fexofenadine, and H-2 receptor antagonist, Famotidine, Nizatidine (2)

Other, over the counter agents for consideration, could include vitamin C, vitamin D and Quercetin. Vitamin C – 500mg as sustained release, can assist in stabilising mast cell and reduce histamine formation and chemical degradation of released histamine (2). Quercetin, a plant based flavonoid, assists in decreasing the production of anti-inflammatory mediators such as prostaglandins (2). Vitamin D, may play a role in the down regulation of MC receptors and dose is dependent on patient serum level (2).

Second line intervention may encompass the introduction of a disodium chromoglycate, acting as a mast cell stabilizer (2). Third line pharmacotherapy may include a second generation H 1 receptor antagonist with an anti-inflammatory effect, Ketotifen and the fourth line, therapy Omalizumab (2), with the latter two pharmacotherapy interventions having application in the patient with refractory gastrointestinal and systemic symptoms (2).

Disorders of the gastrointestinal tract are often complex in their symptom presentation, with stabilising mast cells constituting a promising tool in their management. Frist line therapy encompasses the identification of triggers and dietary modification, to optimise patient outcomes. The skills and expertise of a dietitian with extensive experience are paramount to achieving the best outcome for our patients.

References:

1. Mast Cells in Gastrointestinal Disease. David B. Ramsay, MC, Sindu Stephen, MC, Marie Brown, MC, EdD, MPH, Lysandra Voltaggio, MC, and David B, Doman, MC, FACP, FACG. Gastroenterology & Hepatology Volume 6, Issue 12, December 2010.
2. Mast Cell Activation Syndrome: A Primer for the Gastroenterologist. Leonard B. Weinstock, Laura A Pace, Ali Rezaie, Lawrence B. Afrin, Gerhard J. Molderings. Digestive Diseases an Sciences. https://doi.org/10.1007/s10620-020-06264-9.
3. Mast Cell Activation Syndromes. Cem Akin, MD, PhD, Ann Arbor, Mich. 2017 American Academy of Allergy, Asthma & Immunology. http://dx.doi.org/10.1016/j.jaci.2017.06.007. 
4. Intestinal Mucosal Mast Cells: Key Modulators of Barrier Function and Homeostasis. Merce Albert-Bayo, Irene Paracullellos, Ana M. Gonzalez-Castro, Amanda Rodriguez-Urrutia, Maria J. Rodriguez-Lagunas, Carmen Alonso-Cotonor, Javier Santos and Maria Vicario. Cells 2019. 8., 135;doi:10.3390/cells8020135.

Roux-en-Y Gastric Bypass and Type 2 Diabetes

By Teonie Harland
Consultant Dietitian – Nutritionist
BHlthSc (Nutr & Diet)

Obesity and its potency of co-morbidities, in particular Type 2 Diabetes Mellitus (T2DM) is a burden on the country. With 4.9% of Australians diagnosed with T2DM, the mounting evidence of bariatric procedures to achieve reduction in obesity and reversal of such comorbidities is increasing in commonality(1). Despite reversal being a possibility, it is not a goal in diabetes guidelines nor is it readily advised by the health industry(2)(3).

The Roux-en-Y Gastric Bypass (RYGB) procedure is most advocated for its anti-diabetic effect however, this achievement of almost instantaneous normoglycemia post bariatric procedure is not yet fully understood. All bariatric surgeries initiate caloric restriction postoperatively, however the mechanism, alteration in beta cell function and gut hormones vary thus yielding different response to glycemic index(3). Studies demonstrated that there was greater control of diabetes in RYGB rather than low calorie intake alone in comparison to
weight matched controls(4)(5).The findings suggest that caloric reduction alone does not achieve improved insulin sensitivity and that a combination of responses allows the outcome. After bariatric surgery glucagon-like peptide-1 (GLP-1) receptor stimulation in the gut reduces circulating glucose and thus plays an integral role in maintaining glucose tolerance in T2DM4). The GLP-1 receptor blockade blunted post-prandial response of B-cell
after RYGB having greater impact following surgery when compared to pre-operatively(5)(6). This raises the suggestion that GLP-1 plays a greater role in glucose tolerance and insulin secretion following surgery. Insulin resistance improves between 4-14 days following surgery in both diabetic and non-diabetic patients. Since T2DM creates damage to B-cells function, measuring it is a possible indicator for success of T2DM remission(5)(6)(7).

The secondary hunger appetite regulating hormone peptide YY (PYY) has similar effects to that of GLP-1. The mechanism of PYY induces satiety along with slowing gastric emptying, increasing gastric acid secretion and promoting insulin release. These factors are driven by the dietary consumption of fat and protein. PYY produced by islet cells alongside neuropeptide Y (NYP) receptors exhibit Y1 activation causing the proliferation of B-cells.
This protects them from cell death thereby suggesting that PYY modulates B-cell mass. The secretion of GLP-1 and PYY are higher in post RYGB patients compared to patients preRYGB and also higher than individuals of normal weight, overweight, obese and other weight loss surgeries(8). Following RYGB at 1 year post-surgery those who were considered to have good weight loss had higher PYY levels.

RYGB procedures offers T2DM patients a 76% chance of normoglycemia. However 10% of patients who achieved diabetes remission report relapse between 5 and 16 years postoperatively(4). The combination of pre surgical screening and dietary control can assist with the success rate of post-surgical normoglycemia. The Royal College of General Practitioners (RACGP) recommend screening for patients with Type 2 Diabetes with a c-peptide test alongside full blood count and glucose levels(9). This used in combination with the very low
calorie diet can predict effectiveness of undergoing bariatric surgery. When assessing weight loss achievements post-surgery there was no difference in weight lost even with the comorbidity of T2DM(1)(4).

There continues to be no standardised recommendations for carbohydrate intake requirements for post-surgical RYGB. Even further to this there is no dietary line for treatment for insulin dependent T2DM patients. This irregularity presents the potential for hypoglycemic events post-surgery and the requirements for close contact with the patient and their health care team. The dramatic change on insulin sensitivity post-surgery raises
the question for the need for not only insulin dependent patients but all diabetic patients to monitor blood glucose levels immediately prior to and post-surgery to ensure the effective oral medication and subsequent carbohydrate control due to such varied insulin sensitivity response from 4-28 days post-surgery.

In combination with current first line recommendations of pre-surgical screening, the assessment of B-cell function may provide screening benefit to patients with the comorbidity of T2DM. Further to this orally controlled type 2 diabetics may require blood glucose monitoring post-surgery to ensure glucose stability as insulin sensitivity improves with increasing B-cell function, GLP-1 and PYY receptor activation. This in combination with achieving a 5% total body weight loss prior to surgery and control of carbohydrate intake
under the guidance of a dietitian will further enforce the effectiveness of intervention. The screening and treatment of underlying eating habits or possible eating disorders is essential to identify and treat prior to the consideration of a bariatric procedures all ensuring their longterm success and T2DM reversal.

References

1. Cadena-Obando, D., Ramírez-Rentería, C., Ferreira-Hermosillo, A., Albarrán-Sanchez, A., Sosa-Eroza, E., Molina-Ayala, M., & Espinosa-Cárdenas, E. (2020). Are there really any predictive factors for a successful weight loss after bariatric surgery?. BMC Endocrine Disorders, 20(1). doi: 10.1186/s12902-020-0499-4
2. Smith, F., Holman, C., Moorin, R., & Fletcher, D. (2008). Incidence of bariatric surgery and postoperative outcomes: a population‐based analysis in Western Australia. Medical Journal Of Australia, 189(4), 198-202. doi: 10.5694/j.1326-5377.2008.tb01981.x
3. Vetter, M., Ritter, S., Wadden, T., & Sarwer, D. (2012). Comparison of Bariatric Surgical Procedures for Diabetes Remission: Efficacy and Mechanisms. Diabetes Spectrum, 25(4), 200-210. doi:10.2337/diaspect.25.4.200
4. Lau, R.G., Radin, M., Brathwaite, C., & LouisRagolia (2013). Understanding the Effects of Roux-en-Y Gastric Bypass (RYGB) Surgery on Type 2 Diabetes Mellitus. doi: 10.5772/56398
5. Kashyap, S., Gatmaitan, P., Brethauer, S., & Schauer, P. (2010). Bariatric surgery for type 2 diabetes: Weighing the impact for obese patients. Cleveland Clinic Journal Of Medicine, 77(7), 468-476. doi:10.3949/ccjm.77a.09135
6. Knop, F., & Taylor, R. (2013). Mechanism of Metabolic Advantages After Bariatric Surgery: It’s all gastrointestinal factors versus it’s all food restriction. Diabetes Care, 36(Supplement_2), S287-S291.
doi: 10.2337/dcs13-2032
7. Kassem, M., Durda, M., Stoicea, N., Cavus, O., Sahin, L., & Rogers, B. (2017). The Impact of Bariatric Surgery on Type 2 Diabetes Mellitus and the Management of Hypoglycemic Events. Frontiers In Endocrinology, 8. doi: 10.3389/fendo.2017.00037
8. Beckman, L., Beckman, T., & Earthman, C. (2010). Changes in Gastrointestinal Hormones and Leptin after Roux-en-Y Gastric Bypass Procedure: A Review. Journal Of The American Dietetic Association, 110(4), 571-584. doi:10.1016/j.jada.2009.12.023
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Retrieved 28 February 2021, from https://www.racgp.org.au/afp/2017/july/bariatric%E2%80%93metabolic-surgery-a-guide-for-the-primary-care-physician