There are physiological reasons why your brain feels full up after a day’s work

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Adapted from Medscape, Why our brains wear out at the end of the day, F Perry Wilson Aug 15 2022

We can all recognise from our own experience that as a long day goes on, our performance on mental tasks gets worse. In chess players for example, as the game goes on over several hours, they take longer to make decisions, and they make more mistakes. This is known as cognitive fatigue.

It has been found that the cognitive control centre in the brain is in the left, lateral, prefrontal cortex.(LLFC).

The LLFC is responsible for higher level thinking. It is what causes you to be inhibited. It shuts down with alcohol and leads to impulsive behaviours. It has reduced activity in functional MRI studies as you become more and more cognitively fatigued. The LLFC helps you think through choices. So how does cognitive fatigue happen? As a matter of interest the role of glucose has already been studied and it has been found that this does NOT vary in non- diabetic subjects.

Researchers did experiments with people to induce cognitive fatigue. They had to look at letters and indicate whether the letter was if it was a consonant or a vowel if it was red or if it was upper or lower case if it was green.

Both groups did this for six hours, but one group had much less switching around than the other, so that there was an “easy” group and a “hard” group. They all sounded terribly tedious to me!

The hard group made more mistakes than the easy group, but of course the task was harder to start with. The hard group got a little bit more tired at the end, but both groups were pretty fatigued. The hard group took longer to respond all through the testing hours, but they didn’t take longer by the end of the task. So, overall, there was no clear indicator that could determine who had done the easy tasks or the hard tasks.

The researchers then started adding a new game after the six hours. The subjects were told that they would now play a “reward game”. For instance:

Would you rather have a 25% chance of earning $50 or a 95% chance of earning $17.30?

Would you rather earn $50 but your next task session will be hard or earn $40 and your next task session will be easy?

It has been previously shown that as people become more fatigued they will tend to pick the low- cost choice over the high- win choice. Perhaps we all recognise that after a difficult workday we may be more likely to go with the flow and do something easy rather than the “best” thing. We often don’t feel we have much decision- making power left. I know this is a factor for prescribing more antibiotics on a Friday afternoon.

Interestingly pupil dilatation is a physiologic measure that demonstrates when your brain is “full up”.

When you are interested in something your pupils dilate a little. In the hard group, as time went on, pupil dilatation stopped and constricted in some people. In the easy group however, the dilatation continued through the tasks.

By doing a very fancy labelled hydrogen MRI on the subjects they looked at differences in brain metabolites in the LLPC area of the brain during the tasks.

They found that the level of glutamate and glutamic acid rose in the LLPC but not other metabolites and not in other parts of the brain. They also found that the glutamate leaked from inside the cells to outside the cells.

It is statistically significant that the higher the levels of glutamate in the LLPC, the more likely you are to just make the easy decision as opposed to really think things through.

Perhaps a good night’s sleep is clearing out the excess glutamate in the LLPC and allowing you to perform well the next day.

My comment: The hours pilots and air traffic controllers work are highly regulated because of the effect of fatigue on decisions and performance. Yet, this does not extend to GPs and hospital doctors to anything like the same extent. It is considered important for lorry drivers. For all drivers and for all students, particularly before exams, it is a good idea to recognise that we are all human. Tiredness isn’t something that you can really overcome with will power.

Beta blockers and diuretics are not the best choices for hypertension

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Adapted from Medscape 2 Sept 2022. Hypertension: Real world efficacy of beta blockers versus other anti-hypertensives by Vinod Rane BS Pharm

Patients with hypertension who were treated with ACE inhibitors, Sartans and Calcium Channel blockers such as Amlodipine and Lercanipide had a lower risk of all- cause mortality than those treated with beta blockers.

The risk of all- cause mortality was no different between beta blocker users and those using diuretics.

Cardiovascular mortality was lowest in those treated with ACE inhibitors compared to beta blockers, Sartans, calcium channel blockers and diuretics.

Adapted from Sue Hughes Medscape August 26 2022 TIME: Cardiovascular events similar with evening or morning dose of blood pressure medications.

A five year trial looking at outcomes in those who took their blood pressure medications at night or in the morning showed no difference.

Previous studies have concluded that there could be a benefit to taking anti-hypertensives at night. Dundee researchers headed by Professor Tom MacDonald looked at hard outcomes which included vascular deaths, and non-fatal heart attacks and strokes.

They found “not a smidge of difference” between the two groups.

The study also showed that falls, fractures, or dizzy spells were no more common between the groups. The main thing he said was to take the medications every day at the same time and pick the time that suits you best.

The group tested had an average age of 65, 14% had diabetes,4% smoked,13% had prior CVD and the mean blood pressure at entry was 135/79. The patients were recruited from both primary and secondary care. The duration of follow up was between 5 and 9 years.

My comments: I am aware of the controversies regarding day and night time anti-hypertensives. Some doctors think that blood pressure control is better if drugs are taken at night and some think compliance is better if they are taken in the morning. I take my medication twice a day by splitting the dosage. That way I get good 24 hour coverage and if I forget a dose there is another one coming along in 12 hours or so.

Self- compassion can help students

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Adapted from Human Givens Vol 29 No 1 2022

Over two thirds of university students don’t get enough sleep and this has knock on adverse effects on cognitive function and mental health.

Students have been found to get very stressed and blame themselves for poor academic performance. This leads to anxiety, depression and poor sleep quality. Researchers wanted to find out if treating yourself with kindness and understanding when you are having difficulties improves sleep quality.

Almost 200 students in the University of Manitoba completed questionnaires measuring self- compassion, sleep quality, and emotional regulation.

The researchers found that self- blame was the most important factor which affected low- self compassion. This also affected sleep quality the most. Students who avoided self- blame were also less likely to resort to other unhelpful cognitive strategies when under stress, such as denial, rumination, not making an action plan, catastrophising and assigning negative judgements.

Food factors affecting children

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Adapted from BMJ 20 Nov 21 Vegan diets have mixed effects on children’s health

Dr Malgorzata Desmond from Great Ormond Street Institute of Child Health has studied the effects of a vegan diet in children.

The positive side is that children on vegan diets had less body fat and had a healthier cardiovascular profile but there were also disadvantages.

The vegan children were on average 3cm shorter, had around 5% less bone mineral content and were three times as likely to be deficient in vitamin B12 than meat and dairy eating children.

The findings were from a study of 187 healthy 5 to 10 year olds in Poland. The groups were 63 vegetarians, 52 vegans and 72 meat eaters.

Dr Desmond said that she was also surprised to find that much of the vegan children’s diet came from processed food. She suggests that vegan parents consider giving B12 and Vitamin D supplements to their children.

Adapted from Chang K JAMA Pediatr 14 Jun 2021

Researchers from the Avon Longitudinal Study of Parents and Children Birth Cohort studied children born in the early 1990s from age 7 to 24 years. Three day food and beverage diaries were completed when the children were 7, 10 and 12. Over 17 years BMI, weight, waist circumference and body fat were measured. This is the first study to look at longitudinal associations between ultra processed food intake and health outcomes.

The foods they were looking at included for example: frozen pizzas, mass produced bread, fizzy drinks and ready meals. The groups were split into quintiles for analysis.

The lowest quintile ate 23% of their diet from ultra processed foods and the highest 68%.

The children in the higher consumption groups got fatter quicker. By the age of 24, compared to the lowest ultra processed group, they had a higher BMI by 1.2 kg/m2, higher body fat by 1.5%, were 3.7 kg heavier and had a waist circumference 3.1 cm bigger.

Author Professor Christopher Millet said: We often wonder why obesity rates as so high among UK children and this study gives information why. One in five children are consuming 78% of their calories from ultra processed food.

He suggests that measures to reduce the promotion of these foods and to encourage the eating of normal foods are urgently needed in the UK and globally.

Adapted from Medscape ECO 2021 Parental emotional distress linked to excess weight and fat in offspring 14 May 2021

So are the parents who supply ultra processed food to their children just too overwhelmed to home cook?

Around a third of children in the UK live with at least once parent who experiences significant emotional distress. More than a third of UK children also become overweight or obese by the age of then years.

In the UK Millenium Cohort Study, 19 thousand families born between 2000 to 2002 were tracked. Only two parent households were included in the analysis into parental distress.

Distress in mothers was associated with higher BMIs in girls from the ages of 5 to 14. Distress in fathers was associated with higher BMIs in both girls and boys, compared to undistressed parents.

Supplements for neuropathy, retinopathy, cancer and migraine reduction

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Adapted from Medscape 17 Nov 20, 13 June 21, 20 June 2022 and 26 July 22

Vitamin D

Vitamin D deficiency was significantly associated with an increase in sight threatening diabetic retinopathy (STDR). There was no association seen between vitamin D deficiency and non- sight threatening diabetic retinopathy (NSTDR).

UK researchers conducted a meta-analysis of 12 studies which had enrolled over 9 thousand patients who had type one and type two diabetes who did not have diabetic retinopathy.

Vitamin D deficiency was significantly associated with an increased risk of STDR (OR 1.8 95%)

My comment: For UK residents, particularly in Scotland, it is a good idea to supplement with vitamin D and vitamin K2 at least over our long winter if not all year round. There are many articles about this in previous blog posts which you can search for.

Melatonin

A short- term study of just over 100 patients was undertaken to see if the addition of melatonin to prescribed pregabalin for painful diabetic neuropathy made any difference compared to placebo plus pregabalin.

The groups were split evenly and 6mg of melatonin was tested over an eight -week period compared to an identical placebo.

Sleep improved in both groups but more so with melatonin. Pain also improved for each group and again this was more so in the melatonin group.

On the other hand day- time sleepiness was more pronounced for the melatonin group as was transient dizziness. More patients discontinued in the melatonin group compared to placebo.

My comment: In the UK melatonin is only available on prescription and except for ADHD patients, usually children, it is only given short term to those who have insomnia mainly due to expense. It is available cheaply and widely in supermarkets and pharmacies in the USA and Canada however. For sufferers of painful diabetic neuropathy who live in North America there doesn’t seem much to lose by a trial of treatment. Apart from aiding sleep, which has a host of benefits on its own, Melatonin is an important anti-oxidant. The authors of the study Shokri M et al have not offered an explanation of how they think the melatonin works to reduce pain in the excerpt in Medscape. The full report is at: Shokri M et al, Adjuvant use of melatonin for relieving symptoms of painful diabetic neuropathy: results of a randomised, double blinded, controlled trial. Eur J Clin Pharmacol. 2021 Jun 13.

Ginger

Patients treated with ginger reported significantly less pain, nausea and vomiting compared to placebo in a meta-analysis of 13 RCTs.

Ginger has already been found to improve the pain of osteoarthritis, period pain and muscle pain but had previously given conflicting results regarding migraine.

227 patients were analysed. There were no side effects from the ginger compared to placebo.

My comments: Again, what would you have to lose by trying this if you are a migraine sufferer?

Resistant starch

There is a familial condition called Lynch Syndrome where there is a genetic susceptibility to bowel and other cancers. Recently it has been found that apart from aspirin, resistant starch supplements reduce bowel cancer in this population if taken long term.

Resistant starch is found in oats, breakfast cereal, cooked and cooled pasta or rice, peas and beans and some other starchy foods.

Lead author John Mathers, professor of human nutrition at Newcastle University explains that although resistant starch is a carbohydrate, it is not absorbed in the small intestine and ferments in your large intestine, thereby giving your gut bacteria a good feed. He thinks that it works to reduce bowel cancer by changing the gut bacteria metabolism of bile acids to reduce the kind that damage DNA and eventually cause cancer.

The CAPP2 trial has been following almost one thousand Lynch Syndrome people for between ten and twenty years. They have been taking over this time either: placebo or aspirin or resistant starch. The resistant starch dose is the daily equivalent of eating one unripe banana.

At the end of the first two years there was no difference in effect between the placebo and resistant starch groups on bowel cancer, but cancers in other parts of the body were reduced by 60% in the resistant starch group. The reduced cancers were in the upper gut and included oesophageal, gastric, biliary, pancreatic and duodenal cancers.

Aspirin meanwhile reduced bowel cancer rates by 50% and there was no effect in the placebo group.

Professor Burn said, 30g daily of resistant starch appears to have a substantial effect in Lynch syndrome on non- colorectal cancers and Aspirin works to reduce bowel cancer.

My comments: I wondered if there were resistant starch supplements available but didn’t find any. Eating the sorts of food recommended gave me terrible wind and I gave up!

Genetic discoveries for Motor Neurone Disease and Joint Replacement failures

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Adapted from Medscape 20 June 2022 and 24 June 2022

Throughout my professional career, doctors have never known why some people develop Motor Neurone Disease. This is a devastating condition which leaves the brain intact but weakens the musculature of the body so that most people will have progressive weakness leading to respiratory failure and usually a death from pneumonia within a few years.

Andrew Crosby from Exeter University and others report that a specific gene TMEM63C, affects lipid and cholesterol processing pathways inside brain cells. The area of metabolic dysfunction is between the endoplasmic reticulum and mitochondria.

Dr Julien Prudent PhD states that it is necessary for different organelles within our cells to communicate together by exchanging lipids for example is critical to ensure cellular homeostasis to prevent disease.

There are also other genes known to cause Motor Neurone Disease. It is hoped that more effective diagnostic tools and treatments will eventually have an effect on the impact of the condition in people’s lives.

In another study scientists have discovered a genetic link that shows why some patients develop pain and early failure of their joint replacements.

Cobalt chrome (CoCr) is used in about 70% of artificial joints that are implanted throughout the world.

When a joint replacement fails it causes pain, tissue damage and repeat surgery.

Dr David Langton from Newcastle University explains that a large percentage of joint failures are caused when wear and tear cause small particles from the joint implant to be released into the blood stream and stimulate an immune response in the body. The action is similar to when a person with an organ transplant rejects it. Up until know the reason why some joints are rejected has been unpredictable and unknown.

It has been found that people with some HLA genotypes are at greater risk of CoCr metal sensitivity. This amounts to 10% of the European population.

A collaboration between centres in Newcastle, New York and Perth Australia have produced a machine learning tool called Orthotype which can predict which patients are at higher risk of joint rejection prior to surgery by scanning the patient’s genotype.

In future a great deal of patient misery and expense could be prevented by routine blood testing prior to joint replacement to allow the surgeon to choose the best implant for the individual patient.

At the moment about 10% of the UK population will undergo at least one joint replacement. This number is expected to increase if our weight problems increase too.

NICE: SGLT2 inhibitors will have an increased role in type two diabetes management

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Adapted from BMJ 18 June 2022: Type 2 diabetes: summary of updated NICE guidance

When type 2 patients eventually get their diabetes checks, they can expect a few changes to management if their practices are keeping up with NICE guidelines.

Instead of looking at the 10 year risk for cardiovascular disease, type 2 diabetics over the age of 40 will be assessed for lifetime risk. This is usually a pathway to the initiation of statins, if they are not already being taken. If the cardiovascular risk is raised you will also be considered for an SGLT inhibitor.

If you have chronic heart failure or have already been diagnosed with atherosclerosis you will be considered for an SGLT2 inhibitor. These give a proven cardiovascular benefit.

SGLT2 inhibitors work well with Metformin if a glucose lowering drug is needed.

Modifiable risk factors for diabetic ketoacidosis should be assessed before prescribing SGLT2 inhibitors.

Such factors are: Alcohol limit above 14 units a week, use of illegal drugs, use of other medicines, concurrent illness, injury or planned surgery, very low carbohydrate or ketogenic diet.

There is a decision aid available at:

https://bit.ly/hba1c-nice

NICE: Keep your waist size below half of your height

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Adapted from BMJ 16 April 2022

To reduce the chances of your developing type two diabetes, it is best to keep your belly measurement to less than half of your height. You don’t need a tape measure. A bit of string will do.

NICE say that BMI may still be useful to define overweight and obesity, although it does have considerable limitations in muscular people and in old age. As it is not a direct measure of belly fat which is the driver for diabetes, hypertension and cardiovascular disease it must be interpreted cautiously.

In people of south Asian, Chinese, other Asian, Middle Eastern, black African or African-Caribbean backgrounds NICE are now stating that a BMI of 23 can be considered as overweight and 27.5 can be considered as obese.

These parameters may be important when treatments are being limited by BMI category.

Adapted from Medscape May 25 2022. Why is long term weight loss so difficult? It’s biology, not willpower! by Donna Ryan MD.

When people lose weight changes occur in food regulation hormones and subjective hunger increases. This drives an increase in food intake. The hormones that make you feel full after a meal reduce and the ones that make you hungry increase. Reduced energy expenditure also occurs and this also drives weight regain.

Even when both diet and exercise strategies are applied, regain of more than half of the lost weight occurs by 2 years and 80% of lost weight is regained by 5 years.

People who defy these norms report that they do very high levels of physical exercise, eat low calorie and low- fat diets, have very high degrees of eating restraint, and have low levels of disinhibition. They also tend to weigh themselves several times a week. So, they work really, really hard at it, and can never let up.

The medications that reduce weight work if they are taken for long enough, but on discontinuation, weight gain returns.

What would you like to drink?

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This question is a lot trickier health wise than you think. There has been new research on a variety of beverages that show various harms and benefits.

Coffee

A study from Cambridge suggests that coffee in itself is not a dangerous drink but that thermal damage to the oesophagus is the problem that can result in a higher risk of oesophageal cancer.

In the UK we drink 98 million cups of coffee each day. There are 67 million adults and children in the UK at present to put this into context.

Tea

Green tea is known to confer some health benefits and a recent prospective study has shown benefit for black tea drinkers too. Half a million UK participants in the Biobank cohort were assessed. There is a moderately reduced all-cause mortality reduction in those who have two or more black teas a day. There also was a reduction in mortality from cardiovascular disease, ischaemic heart disease and stroke. There was no effect on cancer mortality or respiratory disease. Surprisingly given the coffee study, there seemed to be no effect from the temperature of the drink or the addition of milk or sugar.

It is thought that substances in the tea improve endothelial function and this is the cause of the effect.

Pre-meal whey protein drink

A small whey protein pre-meal drink taken 10 minutes before meals, significantly reduces mean blood glucose concentration and for diabetic subjects, the amount of time they spend in normal blood sugar ranges.

A placebo RCT was done on 18 people who had type two diabetes who had never been treated with insulin. They were given a 100ml drink containing 15.8g of protein to be taken ten minutes before breakfast, lunch and dinner.

The protein drinkers significantly reduced the prevalence of hyperglycaemia over the day, increased the amount of time in the normal blood sugar range by around 2 hours extra a day, and reduced the 24 hour glucose concentrations. There was no effect on night time blood sugar levels. The acceptability levels of this were high at 98%.

The researchers at Newcastle University say that the protein seems to slow down the speed of gastric emptying and stimulating hormones that reduce the spike in blood sugars.

Alcohol containing drinks

Alcohol is a major preventable risk factor for cancer. About 4-5% of cancers are alcohol related. A new study suggests that reducing alcohol intake reduces the risk of getting an alcohol related cancer in a Korean study.

Those who drink three or more alcohol containing drinks a day are at particular risk of cancer. The heavier drinkers at the outset have the most to gain by cutting down. Some cancers are much more likely from alcohol than others. More than 45 % of mouth and throat cancers are drink related, 25% of laryngeal cancers, 12% of female breast cancers, 11% of colorectal cancers, 10.5% of liver cancers and 7.7% of oesophageal cancers.

Health screenings in Korea were done in 2009 and 2011. The average age was 53 years and they were followed up for just over six years. Over that time, new cancers were seen in 7.7 per thousand of the 4.5 million people screened.

Those who increased their alcohol consumption had a higher increase in cancers. Those who lowered their alcohol intake lowered their risk. The risks were dose related.

Fruit juice, fizzy pop and diet soda

Drinks sweetened with sugar but not natural juices or artificially sweetened drinks were related to a higher risk of inflammatory bowel disease in people who drank more than one a day, in a study of more than 120,000 people.

66% of the people did not drink any sugar sweetened beverages a day but those who consumed more than one such drink a day had a higher BMI and consumed higher amounts of total energy and sugar.

The participants were followed up over ten years. There was a significant increased risk for Crohn’s disease but not for Ulcerative Colitis in the sugary drink consumers. Diet drinks or natural fruit or vegetable drinks had no effect.

All the subjects were over the age of 40 so the effect on the younger population was not studied. Dr Hasan Zaki said that this would be of interest to study because children consume a lot of sugary drinks and the incidence of inflammatory bowel disease in children increased by a third between 2007 and 2016.

My comment: I was pleased to see the beneficial effects of black tea because I drink about 4 pints of it a day. I do like a glass or two of wine with my dinner, but maybe I should cut this down and have a tomato juice or just plain water instead? The pre-meal protein drink looks interesting. I would expect that it would reduce the amount of food consumed at each meal as it should blunt the person’s appetite. I wonder what the longer term effects on weight would be?

Would you eat earlier to improve your blood sugar control?

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Adapted from Diabetes in Control Sept 18 2021: Effects of earlier dinner times on glycaemic control by Andy Dao, Pharm D candidate, University of South Florida.

Growing up you may have heard from your family that eating close to bedtime isn’t a good idea. Eating later has indeed been shown to cause weight gain and metabolic dysfunction. Type 2 diabetes develops 10% more commonly in those who work shifts for instance. It is though that hormonal disruption of the circadian rhythm is the problem.

A recent study looked at how blood sugars were affected by eating earlier than 6pm or after 9pm over the whole 24 hour day. Adults over 20 wore blood sugar monitors over three days in this experiment. They were assigned to have their last meal of the day by 6pm or after 9pm. They had to eat or drink nothing but water after this meal. They were given identical meals three times a day. How they felt, what exercise they took and how well they slept were all assessed.

12 subjects completed the tests. Each group were of comparable height, weight and BMI.

There were significant reductions in blood sugar levels in the early diners in mean blood sugars throughout the whole day, night and early morning. Post prandial levels were also better in the evening for the early diners compared to the late diners but not for breakfast and lunch post prandial levels which were the same regardless of the evening mealtime.

The early diners did report more hunger and capacity to eat in the evenings than the later diners. There was no difference in sleep or physical activity.

So, if you do eat earlier, you can expect improved blood sugars all day long, and perhaps less likelihood of getting diabetes. The downside is more evening hunger. This study was done in healthy non-diabetic people and it would be interesting to see what the results in diabetic subjects would show.

Comment: Sitting down at 5 to 5.30 pm just wouldn’t work well for me, yet this is what we did in my childhood, and we didn’t eat snacks in front of the television after this. In my own house we have dinner at 7.30pm. This however is because I didn’t usually get home before 6.30 pm or even 7pm for many years so an earlier mealtime was not possible for me. I also tend to watch television from 8 pm for about 40 minutes or so before bath and bed. I couldn’t abide eating after 9pm as a regular thing, yet this is very common in Italy. I do think that I would be reaching for the oatcakes and cheese or more if I was in front of the television having eaten at 6pm.