Colorectal cancer is affected by your experience in the womb

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Adapted from BMJ: 18 Sept 2021

A longitudinal study of women from Oakland California has been following 19 thousand of their offspring since the early 1960s.

So far 68 people have been diagnosed with colorectal cancer.

Risk factors include: obesity in the mother, weight gain during pregnancy, and a high birthweight. This suggests that uterine life has something to do with why this cancer develops. This could explain why there has been a relatively recent increase in colorectal cancer in younger aged adults. Unfortunately there is little you can do yourself about these factors.

Women’s health initiative: post menopausal women with cardiovascular disease did worse on a “heart healthy” low fat diet

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Adapted from BMJ: Hiding unhealthy heart outcomes in a low fat diet trial: The Women’s health initiative randomised controlled dietary modification trial finds that post menopausal women with established coronary heart disease were at increased risk of an adverse outcome if they consumed a low fat “heart healthy” diet. by Timothy David Noakes. Open Heart. 2021.

The WHI trial was designed to test with the US Department of Agriculture’s 1977 Dietary Guidelines for Americans protects against coronary heart disease (CHD) and other chronic diseases.

The only significant finding was that post menopausal women with CHD randomised to a low fat diet in 1993 were at a 26% greater risk of developing additional CHD events compared to women eating the control diet. In 2017 an additional 5 years of follow up data was published. It found that the risk for this group of women had increased to 47-61%.

The authors sought to explain why this was but author Tim Noakes has looked at the evidence and his opinion is that the women who had consumed 13 years of a low fat/high carbohydrate diet had inadvertently succumbed to the features of insulin resistance. Their risk of type 2 diabetes went up almost eleven fold and metabolic syndrome went up six fold.

Dr Noakes advises that according to the principle of “do no harm” the practice of putting women on low carb diets if they are diagnosed with cardiovascular disease is certainly not evidence based and probably not ethical.

The WHI is one of the most expensive long term dietary intervention trials ever undertaken. It started in 1993. Although the advice was given to cut dietary fat, particularly saturated fat in 1977, the policy had never actually been tested regarding its effects on weight, CHD, cancer and type two diabetes.

The idea was to replace the calories from saturated fat with increased carbohydrates from grains, fruits and vegetables. The effect of this was to lower blood cholesterol concentrations. The trial did not seek to replace saturated fat with polyunsaturated fat as studies of this had been published in 2013 and 2016.

Nutritionists led the first year 18 group sessions followed by individual follow up every 3 months. Feedback was given so as to encourage low fat intake.

A low fat diet was not found to improve rates of breast cancer, colorectal cancer, and only resulted in 0.4 kg weight loss over the first 8 years of the trial. The more women adhered to the low fat diet, the more weight they gained. The women who ate high fat, lower carb diets, the more weight they lost.

Blood sugar started to deteriorate in the first year of the trial for the low fat diet group. Post menopausal women who went on statins were at a 49% increased risk of developing type two diabetes. A prior meta-analysis had found that there was a 9% chance of developing type two diabetes with statin use.

The 2017 report analysed women in subgroups: No CHD or hypertension. Hypertension only. and pre-existing CHD. The idea was to see who may benefit or lose the most from the low fat intervention.

Women with hypertension only had neither benefit or harm from the low fat diet. Women who had no pre-existing hypertension or CHD had a small reduction in CHD risk but this was off set by a higher risk of stroke.

Regarding another study, the ERA trial, women who were on HRT who reported that they ate the most saturated fat over the trial time of three years, found that their coronary atheroma did not progress. In fact there was a modest regression in coronary artery narrowing. Both those who ate the most polyunsaturated fat, and those who ate the highest amount of carbohyrate and therefore the lowest amount of total fat showed worsening of their coronary atheroma.

Statin use was similar in both groups who were randomised to each diet, low fat versus usual. Indeed more than 40 percent of the women in each group were on statins.

Only post menopausal women who do not have CHD or hypertension are safe to eat the low fat diet, the others can expect some negative effects.

The Women’s health study (WHS) was established between 1992 and 1995 at Harvard Medical School to look into the effects of aspirin and vitamin E on the risks of developing CHD or cancer in women who started off with neither condition.

The study showed no benefit for either treatment.

A 21 year follow up programme of over 2,800 of these women evaluated more than 50 different clinical, lipid, inflammatory and metabolic factors.

Results showed that the development of Type two diabetes, and not high cholesterol levels were important factors in the development of CHD. Hypertension gives a 4.58 fold increase in CHD. Obesity gives a 4.33 fold risk. These factors as well as type two diabetes and metabolic syndrome were more predictive of CVD than smoking.

A Lipoprotein Resistance Score was developed looking at various factors particularly VLDL and HDL and a high level produced a 6.4 fold risk of cardiovascular disease. This is worsened in insulin resistance. LDL scores only gave a 1.38 fold risk of CVD by comparison.

The Progression of Early Subclinical Atherosclerosis Study looked at HbA1c in people who did not have type two diabetes. The higher the HbA1c, the higher the risk of CVD and the risk even started below HbA1c levels of 5.5%.

Women who had low HDL levels was associated with a higher breast cancer incidence and all cause mortality after breast cancer as well as an increased risk of cancer specific and all cause mortality.

The Recovered Minnesota Coronary Experiment (RMCE) study found that people randomised to eat more polyunsaturated fat in place of saturated fat were at a 22% higher risk of death with each 0.78 mmol/L reduction in blood cholesterol. This effect was worse in the over 65s.

The Recovered Sydney Diet Heart Study (RSDHS) showed that replacement of dietary saturated fat with linoleic acid was also associated with raised all cause mortality with increased deaths from cardiovascular disease and coronary heart disease.

Lawrence ( Lawrence GD Perspective: the saturated fat- unsaturated oil dilemma: relations of dietary fatty acids and serum cholesterol, atherosclerosis, inflammation, cancer and all cause mortality. Adv Nutr. 2021; 12: 647-56) concluded: PUVAs are unstable to chemical oxidation and their oxidation products are harmful in a variety of ways. They can initiate inflammation that can have dire health consequences. If saturated fats are replaced by carbohydrates in the diet there would be no significant improvement in serum cholesterol and it can result in a more atherogenic lipoprotein profile. …It appears that saturated fats are less harmful than the common alternatives.

This set of findings from four different studies effectively ends the debate about which diet should be eaten to lower the risk of CVD, especially in those with insulin resistance.

Two diets shown to prevent the clinical features of IR leading to type two diabetes are the restricted low calorie diet developed by Lim et al (Lim et al. Reversal of type two diabetes; normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetalogica 2011;54:2506-14.) and the ad libitum low carbohydrate higher healthy fat ketogenic diet.(Hite AH et al. In the face of contradictory evidence: report of the dietary guidelines for Americans Committee. Nutrition 2010;26:915-24.)

It is the ethical responsibility of those who manage those with cardiovascular disease or diabetes or other insulin resistance that they should NOT prescribe the never proven and now disproven low fat “heart healthy” DGA diet.

It is really hard to lose weight!

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A survey of overweight adults from six countries in western Europe found that most strategies didn’t work.

The analysis was lead by diabetologist Dr Marc Evans from Cardiff said, ” It is important that we tackle Europe’s growing obesity problem to reduce hospitalisation from the multiple illnesses that result. Our survey results show that most adults with obesity are actively trying to address this, but most are unsuccessful whatever strategy they choose”.

The study looked at 1,850 adults from the UK, France, Germany, Italy, Spain and Sweden. All had BMIs of 30 or more. A quarter of the participants reported no ill effects from being overweight and the others commonly reported high blood pressure, lipid abnormalities and type two diabetes. 78.6% of them had tried to lose weight the previous year.

The most common methods used were: Calorie controlled or restricted diet 71.9%, an exercise programme 21.9%, drug treatment 12.3%, joining a gym 12%, using a digital health app 9.7%, alternative treatments 8.1%, weight loss service 7%, and cognitive behavioural therapy 2.1%.

The results were that 78% of those who attempted to lose weight did not lose 5% or more of their initial weight and some weighed more than this afterwards.

For those who tried calorie controlled or restricted diets 26.5% of people did lose weight but 17.1% of them gained weight.

For those who undertook an exercise programme 33.3% lost weight but 15.5% gained weight.

The gym goers lost weight 27% of the time but 32.4% gained. (We don’t know if this was muscle gain or fat gain though)

It seems that apart from baratric surgery few interventions achieve long term weight loss but an article in iScience published in 2021 found that health effects of obesity were considerably reduced or eliminated by having moderate or high levels of cardiorespiratory fitness. It argued that it might be better to emphasise the benefits of physical activity than stress weight loss as being the most important goal.

Meanwhile results from 80 thousand participants in the UK Biobank cohort show that more time spent in moderate to vigorous activity is associated with lower mortality. It doesn’t matter if you do these higher levels of activity in one go or in multiple bouts.

Healthy life expectancy falls for those in less affluent areas in the UK

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Adapted from BMJ 30 April 2022

The National Office for Statistics from 2018 to 2020 show that men born in the poorest areas of the UK are expected to live ten years less than men from the most affluent areas. Poor men can expect to live a healthy life till the age of 52 and die around the age of 73. Wealthy men may expect to live in good health till they are 67 and die around the age of 83.

Women in the poorest areas can expect 19 fewer years in health compared to wealthier women. They can expect to be healthy in poor areas till they are 52 and this is 71 for wealthy women. Women in poor areas can expect to die around the age of 70 and wealthy women around the age of 86.

There has been a bit of a decrease in life expectancy generally in the last few years, pre-covid. David Finch of the Health Foundation says that improvement in incomes is needed to cope with the rising cost of living, secure jobs and decent housing.

My comment: What goes on at the doctor’s surgery and hospitals is just the tip of the iceberg regarding health. Housing, employment, a good diet, access to green spaces, social interaction, education, good transport, reduced pollution, clean water, freedom from violence, and good health behaviours such as diet and exercise habits, known collectively as the social determinants of health are much more important. Policies that will improve these factors are necessary to improve the situation. I would argue that living a healthy life is more important than an extra few years in a nursing home.

Fibromyalgia likely due to autoimmune attack

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From Geobel A et al Journal of Clinical Investigation 1 Jul 2021

Many of the symptoms in fibromyalgia syndrome (FMS) are caused by antibodies increasing the activity of pain sensing nerves throughout the body according to new research led by the Institute of Psychiatry, Psychology and Neuroscience at King’s College London.

This is at odds of the currently held view that the condition arises centrally in the brain.

The researchers injected mice with antibodies of people who have FMS and saw that the mice rapidly developed increasing sensitivity to pressure and cold as well as reduced movement grip strength.

In contrast, mice who were injected with antibodies from healthy people were unaffected.

The injected mice recovered from their symptoms after a few weeks once they had cleared the antibodies from their systems. The researchers wonder if treatments that would reduced antibodies in patients with FMS could become an effective treatment.

Dr David Andersson, the lead investigator said, ” Treatment for FMS is currently focused on gentle aerobic exercise, and drug and psychological therapies designed to manage pain, although these have been proven to be ineffective in patients. There is an enormous unmet clinical need. Our work has uncovered a whole new area of possible therapeutic options and should give real hope to fibromyalgia patients”.

Eggs really are good for you!

For any lingering controversy regarding eggs and cholesterol and heart disease, this new study reveals a considerable association between egg eating and a reduction in cardiovascular disease.

Meta-Analysis Am J Med

. 2021 Jan;134(1):76-83.e2. doi: 10.1016/j.amjmed.2020.05.046. Epub 2020 Jul 10.

Association Between Egg Consumption and Risk of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis

Chayakrit Krittanawong 1Bharat Narasimhan 2Zhen Wang 3Hafeez Ul Hassan Virk 4Ann M Farrell 5HongJu Zhang 5W H Wilson Tang 6Affiliations expand

Abstract

Introduction: Considerable controversy remains on the relationship between egg consumption and cardiovascular disease risk. The objective of this systematic review and meta-analysis was to explore the association between egg consumption and overall cardiovascular disease events.

Methods: We systematically searched Ovid MEDLINE, Ovid Embase, Ovid Cochrane Database of Systematic Reviews, Scopus, and Web of Science from database inception in 1966 through January 2020 for observational studies that reported the association between egg consumption and cardiovascular disease events. Two investigators independently reviewed data. Conflicts were resolved through consensus. Random-effects meta-analyses were used. Sources of heterogeneity were analyzed.

Results: We identified 23 prospective studies with a median follow-up of 12.28 years. A total of 1,415,839 individuals with a total of 123,660 cases and 157,324 cardiovascular disease events were included. Compared with the consumption of no or 1 egg/day, higher egg consumption (more than 1 egg/day) was not associated with significantly increased risk of overall cardiovascular disease events (pooled hazard ratios, 0.99; 95% confidence interval, 0.93-1.06; P < .001; I² = 72.1%). Higher egg consumption (more than 1 egg/day) was associated with a significantly decreased risk of coronary artery disease (pooled hazard ratios, 0.89; 95% confidence interval, 0.86-0.93; P < .001; I² = 0%), compared with consumption of no or 1 egg/day.

Conclusions: Our analysis suggests that higher consumption of eggs (more than 1 egg/day) was not associated with increased risk of cardiovascular disease, but was associated with a significant reduction in risk of coronary artery disease.

Keywords: Acute myocardial infarction; Cardiovascular disease; Egg consumption; Meta-analysis; Stroke; Systematic review.

Over 40s can benefit from red light therapy

Adapted from Shinhmar H et al. J Gerontol A Biol Sci Med Sci 29 Jun 2020

It sounds like a hoax, but staring at a deep red light for three minutes a day has been found by researchers to significantly improve declining eyesight in people aged over 40.

This is the first study of its kind in humans and it was conducted in the UK.

At around the age of 40, human retinal cells start degenerate increasingly rapidly and this causes visual deterioration.

It had already been discovered that retinal photoreceptors in animals improved if they were exposed to 670 nm deep red light.

For the study 24 people aged between 28 and 72 with no retinal disease were recruited. The gender balance was equal. The function of their rods and cones on the retina were tested. Then they were given a special pen torch which emitted the deep red light and they were told to use this for three minutes a day for two weeks.

The light had no effect in the under 40s but after this colour sensitivity improved by up to 20 per cent, particularly in the blue parts of the spectrum, which is particularly affected by ageing. Rod sensitivity also improves. This helps people to see in low levels of light.

Lead author Professor Glen Jeffrey said,” Our study shows that it is possible to significantly improve vision that has declined in aged individuals using simple brief exposures to light wavelengths that recharge the energy system that has declined in the retina cells, rather like re-charging a battery.”

My comment: I am very shortsighted and as a result of my eye shape I have very poor night vision. If these little torches were made available I would definitely use one.

Blood pressure difference between arms can be a risk factor for cognitive decline…as well as other things.

From Systolic inter-arm blood pressure difference and cognitive decline in older people, a cohort study. Christopher E Clark. BJGP July 2020

 

A prospective study was done in 1,113 Italians whose average age was 66.4 years. Even a difference of only 5 degrees between the arms was associated with a greater level of cognitive decline.

My comment: In UK GP practices, only one arm is used to check the blood pressure. In my case, it was the arm that was nearest to the desk. Perhaps we should check both ? Inter-arm BP differences are both associated with cardiovascular disease, and this in turn affects dementia. Then of course, is the question, what can you do about it? For a further discussion of the subject here is Pharmacist Antonio Bess from Diabetes in Control.

Cognitive Decline: Just Life, or a Preventable Disease?
Feb 22, 2020

Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Antonio Bess, Pharm D Candidate, Florida Agricultural & Mechanical University School of Pharmacy

Cognitive decline is associated with many diseases and medications, but the exact mechanisms are not clearly understood.
Diabetes, obesity, and declining cognitive function are all associated with increased prevalence with increasing age.

Diabetes is a known risk factor for eye, kidney, neurological and cardiovascular diseases, but its effect on declining cognitive function has been in question. Previous studies have found associations between patients who have diabetes and poor glycemic control and significantly faster cognitive decline. Other studies have demonstrated a pattern in which diabetes, high blood pressure, and high body mass index in midlife predict dementia in late life.

In this prospective study, individuals were followed for up to ten years to find associations between indices in diabetes, insulin resistance, obesity, inflammation, and blood pressure with cognitive decline. The indices of interest were measured separately among those with and without central obesity.
The Monongahela‐Youghiogheny Healthy Aging Team is a population‐based cohort of participants recruited randomly from 2006 to 2008, who were 65 and older, and were from a group of small towns in southwestern Pennsylvania. The study is focused on the epidemiology of cognitive decline and dementia in an area that still has not recovered economically from the collapse of the steel industry in the 1970s.

Participants were analyzed at study entry, and annual follow up. To measure cognitive function, participants were given a panel of neuropsychological tests tapping the domains of attention/processing speed, executive function, memory, language, and visuospatial function. At study entry and annually, BP, BMI, waist‐hip ratio, and depressive symptoms  were measured.
Key variables at the time of blood draw, including age, sex, race (white vs. nonwhite), education (high school [HS] or less vs. more than HS), APOE*4 allele carrier status, mCES‐D score, BMI, WHR, systolic BP (SBP), and the following laboratory assay variables: CRP, glucose, HbA1c, insulin, HOMA‐IR, resistin, adiponectin, and GLP‐1 were all reviewed to identify predictors of cognitive decline.
Among 1982 participants who were recruited and underwent full assessment at baseline from 2006 to 2008, only 478 individuals were able to provide fasting blood samples. Of this group of individuals, the median age was 82 years; 66.7% were women; 96.7% were white, and 49.0% had more than HS education.

Compared to the 1504 original participants without fasting blood data, at baseline, these 478 were significantly younger (74.6 vs. 78.6 years; P < .001); more likely to be women (66.7% vs. 59.2%; P = .004); more likely to be of European descent (96.7% vs. 94.1%; P < .001); more likely to have at least HS education (49.0% vs. 38.6%; P < .001); but about equally likely to be APOE*4 carriers (19.3% vs. 21.5%; P = .350).
In unadjusted analysis in the sample as a whole, faster cognitive decline was associated with greater age, less education, APOE*4 carriage, higher depression symptoms (mCES‐D score), and higher adiponectin level. HbA1c was significantly associated with cognitive decline.

After stratifying by the median waist-hip ratio, HbA1c remained related to cognitive decline in those with higher waist-hip ratios. Faster cognitive decline was associated, in lower waist-hip ratio participants younger than 87 years, with adiponectin of 11 or greater; and in higher waist-hip ratio participants younger than 88 years, with HbA1c of 6.2% or greater. Higher adiponectin levels predicted a steeper cognitive decline in the lower waist-hip ratio group.
Abdominal obesity plays a crucial role in cognitive decline in those with diabetes. The microvascular disease may play a more significant role than macrovascular disease. Midlife obesity contributes to cognitive decline but there was no midlife data in this study. Future studies should include a large minority, midlife population. Adiponectin levels need to be carefully assessed as well.

Practice Pearls:
In individuals younger than 88 years old, central obesity can lead to faster cognitive declines.
Obesity, diabetes, and aging contribute to cognitive decline, so it’s hard to distinguish the most significant risk.
Adiponectin may be a novel independent risk factor for cognitive decline and should be reviewed.

Ganguli, Mary, et al. “Aging, Diabetes, Obesity, and Cognitive Decline: A Population‐Based Study.” Journal of the American Geriatrics Society, John Wiley & Sons, Ltd, Feb. 2020, p. jgs.16321, doi:10.1111/jgs.16321.
Ganguli, Mary, et al. Aging, Diabetes, Obesity, and Cognitive Decline: A Population-Based Study. 2020, pp. 1–8, doi:10.1111/jgs.16321.
Tuligenga, Richard H., et al. “Midlife Type 2 Diabetes and Poor Glycaemic Control as Risk Factors for Cognitive Decline in Early Old Age: A Post-Hoc Analysis of the Whitehall II Cohort Study.” The Lancet Diabetes and Endocrinology, vol. 2, no. 3, Elsevier Limited, Mar. 2014, pp. 228–35, doi:10.1016/S2213-8587(13)70192-X.
Cukierman, T., et al. “Cognitive Decline and Dementia in Diabetes – Systematic Overview of Prospective Observational Studies.” Diabetologia, vol. 48, no. 12, Springer, 8 Dec. 2005, pp. 2460–69, doi:10.1007/s00125-005-0023-4.

Antonio Bess, Florida Agricultural and Mechanical University College of Pharmacy

Dietary gluten in pregnancy is related to an increased risk of type one diabetes in the child

Adapted from Antvorskov JC et al. Association between maternal gluten intake and type one diabetes in offspring. BMJ 22 September 2018

This research was based on a study of Danish women’s food frequency questionnaires completed 25 weeks after their first pregnancies ended. The incidence of diabetes in the children was then noted from January 1996 till May 2016 from the Danish Registry of Childhood and Adolescent Diabetes. After certain exclusions had been made over 63,500 were analysed.

The mean gluten intake per day was 13g ranging from 7g to more than 20g per day.

The incidence of diabetes in the child increased proportionately according to gluten intake. The women who had  20g or more intake had double the type one diabetes in their offspring compared to those who ate 7g or less.

As type one diabetes has risen seemingly inexplicably over the last few decades, there has been a lot of consideration into possible environmental triggers. Gluten is a storage protein found in wheat, rye and barley.  In animal studies, a wheat free diet in the mother has been found to dramatically reduce the incidence of diabetes in the child.

It has been suggested that gluten can affect gut permeability, gut microbiotica and cause low grade inflammation.

Although there is this association between gluten and type one diabetes it could be that other factors, for example the advanced glycation products from the baking process, that are to blame.  Unwanted additives to grain  could also be a factor eg mycotoxins, heavy metals, pesticides and fertilisers.

Mothers who eat a lot of gluten may similarly feed their children a lot of gluten. They also may pass gliadin from wheat into the breast milk.

Although this research suggests that high amounts of gluten may be problematic in pregnancy, further research will need to be done before dietary recommendations are likely to be changed.

Wondering if fasting is worth the pain?

Carbohydrate restriction regulates the adaptive response to fasting
S. Klein and R. R. Wolfe 
Department of Internal Medicine, University of Texas Medical Branch, Galveston.
The importance of either carbohydrate or energy restriction in initiating the metabolic response to fasting was studied in five normal volunteers.

The subjects participated in two study protocols in a randomized crossover fashion. In one study the subjects fasted for 84 h (control study), and in the other a lipid emulsion was infused daily to meet resting energy requirements during the 84-h oral fast (lipid study).

Glycerol and palmitic acid rates of appearance in plasma were determined by infusing [2H5]glycerol and [1-13C]palmitic acid, respectively, after 12 and 84 h of oral fasting.

Changes in plasma glucose, free fatty acids, ketone bodies, insulin, and epinephrine concentrations during fasting were the same in both the control and lipid studies.

Glycerol and palmitic acid rates of appearance increased by 1.63 +/- 0.42 and 1.41 +/- 0.46 mumol.kg-1.min-1, respectively, during fasting in the control study and by 1.35 +/- 0.41 and 1.43 +/- 0.44 mumol.kg-1.min-1, respectively, in the lipid study.

These results demonstrate that restriction of dietary carbohydrate, not the general absence of energy intake itself, is responsible for initiating the metabolic response to short-term fasting.