Tag Archives: Diet

Antioxidants and Age-Related Macular Degeneration

It is estimated that around 5% of the general population suffer from age-related macular degeneration (AMD),[1] where extracellular material known as drusen accumulate under the retina at the back of the eye and which can eventually lead to blurred or a loss of vision. It has been suggested that antioxidants may help prevent or delay development of AMD in people who do not suffer the condition by protecting the retina against oxidative stress, but it is unclear as to whether this is the case.

A systematic review in the Cochrane Database by Evans and Lawrenson looked at the effectiveness of antioxidant supplements as treatment in people who already had AMD,[2] and found that taking a multivitamin antioxidant vitamin may delay the progression of AMD when compared to a placebo or no treatment (odds ratio 0.72, 95% CI 0.58-0.90). The authors also conducted a systematic review looking at whether there was an association between taking antioxidant vitamins (carotenoids, vitamin C, vitamin E) or minerals (selenium, zinc) and the development of AMD in people without AMD.[3] Five RCTs were included, with a total of 76,756 individuals without AMD. These studies all looked at the use of various supplements against placebo. Generally, the various studies found that there was no effect of supplements on development of AMD, while in some cases there was evidence of an increased risk (see table below).

Comparison No. of studies Disease Risk Ratio (95% Confidence Interval)
Vitamin E vs. placebo 4 AMD 0.97 (0.90-1.06)
Late-stage AMD 1.22 (0.89-1.67)
Beta-carotene vs. placebo 2 AMD 1.00 (0.88-1.14)
Late-stage AMD 0.90 (0.65-1.24)
Vitamin C vs. placebo 1 AMD 0.96 (0.79-1.18)
Late-stage AMD 0.94 (0.61-1.46)
Multivitamin vs. placebo 1 AMD 1.21 (1.02-1.43)
Late-stage AMD 1.22 (0.88-1.69)

— Peter Chilton, Research Fellow


  1. Owen CG, Jarrar Z, Wormald R, Cook DG, Fletcher AE, Rudnicka AR. The estimated prevalence and incidence of late stage age related macular degeneration in the UK. Br J Ophthalmol. 2012; 96(5): 752-6.
  2. Evans JR, Lawrenson JG. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration. Cochrane Database Sys Rev. 2017; 7: CD000254.
  3. Evans JR, Lawrenson JG. Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration. Cochrane Database Sys Rev. 2017; 7: CD000253.

Improving Access to Fresh Food in Low-Income Areas

In a previous News Blog we looked at a paper that found an association between adherence to the Mediterranean diet (i.e. high consumption of fruit, vegetables, and legumes) and reduction in cardiovascular disease risk.[1] So, it can be argued, that for those in low-income areas there is a need to improve their access to fresh fruit and vegetables. But how best to achieve this? Breck and colleagues, on behalf of the CDC, looked at one possibility in a cross-sectional survey analysis.[2]

Previously, the city of New York had attempted to address the issue by granting new licenses for mobile fruit and vegetable carts in those neighbourhoods with poor availability of fresh food. However, only some of the carts (27%) had the capacity to accept the Supplemental Nutrition Assistance Program (SNAP) benefits (a federal aid program to provide food-purchasing assistance) through use of Electronic Benefit Transfer (EBT) machines.

The authors conducted a survey analysis of 779 adults shopping at four carts in the Bronx neighbourhood of New York over several time periods. After controlling for cofounders, they found that those shoppers who were able to pay using their SNAP benefits purchased significantly (p<0.001) more fruit and vegetables (an average of 5.4 more cup equivalents), than those who were only able to pay with cash. While there are promising results from providing consumers with more ways to pay, there are challenges that could prevent widespread roll out of EBT, chiefly the high initial, monthly, and transaction fees that the cart vendors need to pay. Even when provided with financial support, less than one-third of carts were equipped with EBT machines at the time of this study. Although the study has a number of limitations that means causal inferences cannot be drawn, it can be seen as a possible avenue for future research.

— Peter Chilton, Research Fellow


  1. Chilton P. Diet and Socioeconomic Status. 18 August 2017.
  2. Breck A, Kiszko K, Martinez O, Abrams C, Elbel B. Could EBT Machines Increase Fruit and Vegetable Purchases at New York City Green Carts? Prev Chronic Dis. 2017; 170104.

How Much Fruit and Veg is Enough?

We are often told that we should be eating five (or is it now ten?) portions of fruit and vegetables each day to protect against, amongst other things, cardiovascular disease (CVD).[1] However, such recommendations are generally based on research conducted in people from Europe, the USA, Japan and China. There is little data from countries in the Middle East, South America, Africa or South Asia.

The PURE study (Prospective Urban Rural Epidemiology) set out to rectify this, recruiting 135,000 participants from 18 countries, ranging from high-income countries, such as Sweden, to low-income countries, such as India.[2] The research team documented the diet of these individuals at baseline (using questionnaires specific to each country), then followed them up for a median of 7.4 years, looking at cardiovascular-related clinical outcomes. As expected higher intakes of fruit, vegetables and legumes were associated with lower incidences of major CVD, myocardial infarction, and mortality (cardiovascular-related and all-cause). However, the hazard ratio for all-cause mortality was lowest for three to four servings (375-400g) per day (0.78, 95%CI 0.69-0.88), with no significant decrease with higher consumption.

It is more likely that consuming around 375g of fruit/vegetables/legumes per day will be within the financial reach of people living in poorer countries, compared to the various recommendations of 400-800g that are often seen in Europe and North America. Before we ditch that extra snack of carrot sticks, however, it is important to note that factors such as food type, nutritional quality, cultivation and preparation are likely to vary between countries, while other clinical outcomes, such as cancer, were not looked at in this study.

The authors are continuing to enrol more participants, and are hoping to re-examine their results in the future.

— Peter Chilton, Research Fellow


  1. Oyebode O, Gordon-Dseagu V, Walker A, Mindell JS. Fruit and vegetable consumption and all-cause, cancer and CVD mortality: analysis of Health Survey for England data. J Epidemiol Community Health. 2014; 68(9): 856-62.
  2. Miller V, Mente A, Dehghen M, et al. Fruit, vegetable, and legume intake, and cardiovascular disease and deaths in 18 countries (PURE): a prospective cohort study. Lancet. 2017.

Should You Keep Drinking Coffee?

It is nice, at last, to find something that is it is really enjoyable and that is good for us. Recent News Blogs have carried articles on the harmful effects of red meat,[1] milk,[2] and alcohol.[3] But what about coffee? A recent article, based on over 500,000 people in ten European countries confirmed the already extensive literature showing that coffee is beneficial for health.[4] In fact, overall death rates were reduced by over 10%. There was a massive (over 50%) reduction in diseases of the digestive system, confirming the well-known beneficial effect of coffee on the liver. The trend was also favourable for heart disease and stroke. Many biochemical markers also moved in a favourable direction, including glycated haemoglobin, and C-reactive protein. The only bit of bad news pertained to ovarian cancer, where a 30% increased risk of death was noted. Reverse causality is always a possibility in non-experimental studies, even if, like this one, they are prospective. However, this is unlikely since the hazard ratios were unaltered if patients who died within eight years of recruitment were excluded.

— Richard Lilford, CLAHRC WM Director


  1. Lilford RJ. An Issue of BMJ with Multiple Studies on Diet. NIHR CLAHRC West Midlands News Blog. 4 August 2017.
  2. Lilford RJ. Two Provocative Papers on Diet and Health. NIHR CLAHRC West Midlands News Blog. 12 December 2014.
  3. Lilford RJ. Alcohol and its Effects. NIHR CLAHRC West Midlands News Blog. 18 August 2017.
  4. Gunter MJ, Murphy N, Cross AJ, et al. Coffee Drinking and Mortality in 10 European Countries. Ann Intern Med. 2017; 167: 236-47.

Diet and Socioeconomic Status

People looking to lose weight and/or get healthy try a wide variety of diets, from fad diets with highly specific restrictions on what can be eaten, to general healthy eating plans. One such nutritional recommendation is the Mediterranean diet, based on the “food patterns typical of Crete… Greece and southern Italy…”,[1] and entails consumption of high amounts of plant foods (fruit, vegetables, cereals, legumes, etc.) and olive oil, moderate amounts of dairy, fish and wine, and low amounts of poultry and red meat. A number of observational studies have shown associations between such a diet and lower incidences of cardiovascular disease (CVD) and associated mortality, cancer, neuro-degenerative disorders, and overall mortality. However, there is uncertainty whether such benefits differ across different socioeconomic groups.

Bonaccio et al. carried out a prospective analysis of nearly 19,000 Italians to see the effect of the Mediterranean diet on CVD.[2] While there was an overall reduction in CVD risk associated with adherence to the diet (HR=0.85, 95% CI 0.73-0.99), this was not seen across all socioeconomic groups – only in those who were educated to a postgraduate or higher level (HR=0.43, 0.25-0.72) and in those with a high (>€40,000) household income (HR=0.39, 0.23-0.66). Those with less education (HR=0.94, 0.78-1.14) and lower income (HR=1.01, 0.79-1.29) had no significant association. Why such a difference? Subgroup analysis of people with similar adherence to the diet showed that there were a number of differences in the diet of those with high compared to low education, and those with high compared to low income. These included consumption of organic vegetables (which would have higher antioxidants and lower levels of pesticides), monounsaturated fatty acids (found in avocado, nuts, olives, etc.), micronutrients, and whole-grain bread, as well as greater dietary diversity.

So perhaps it is more important to make sure the food you are eating is of high quality and varied, than just simple healthy eating. Of course, access to high quality food of high nutritional value is not easy for poor people.

— Peter Chilton, Research Fellow


  1. Willett WC, Sacks F, Trichopoulou A, Drescher G, Ferro-Luzzi A, Helsing E, Trichopoulos D. Mediterranean diet pyramid: a cultural model for healthy eating. Am J Clin Nutr. 1995; 61(6): 1402S–6S.
  2. Bonaccio M, Di Castelnuovo A, Pounis G, et al. High adherence to the Mediterranean diet is associated with cardiovascular protection in higher but not in lower socioeconomic groups: prospective findings from the Moli-sani study. Int J Epidemiol. 2017.

An Issue of BMJ with Multiple Studies on Diet

This News Blog often contains information about diet and health. For example, we have cited evidence that salt is enemy number one [1]; trans-fats are unremittingly bad news [2]; and large amounts of sugar are harmful.[3] After that the risks become really rather small – relative risks of about 20%. Fruit, and more especially vegetables, are good news. Milk is an unhealthy drink in adults (never intended for that purpose and galactose is harmful, unless removed during a fermentation process).[4] Three further studies of diet were included in a single recent issue of the BMJ.[5-7]

The first study by Etemadi, et al. looked at meat consumption in a large cohort of people (n= 536,969) who gave detailed dietary histories.[5] The evidence corroborates other studies in showing that red meat is harmful, increasing relative risk of death by about 20% in high meat eaters compared to moderate meat eaters. The difference is greater if the comparison is made with people who obtain almost all of their meat in the form of fish and chicken. The causes of death that showed greatest increases in risk with high red meat consumption were cancer, respiratory disease and liver disease. Surprisingly, perhaps, increased risk from stroke was nugatory. The increased risk in unprocessed meat is probably related to haem iron, and in processed meat to nitrates/nitrites – there are all pro-oxidant chemicals. Of course this is an association study, so some uncertainty remains. The main problem with meat, as the BMJ Editor points out,[8] is the harmful environmental effects; apparently animal husbandry contributes more to global warming than burning fossil fuels. I take the environmental effects seriously – perhaps we will one day vilify meat farmers more vociferously than we currently vilify tobacco farmers. After all, individuals don’t have to smoke, but cannot protect themselves from the harmful effects of pollution.

Meanwhile, for those who are interested, the other two relevant articles in this issue of the BMJ looked at avoiding gluten in people who do not have celiac disease (no benefit and evidence points towards harm),[6] and the beneficial effect of a low salt and fat diet on gout.[7]

— Richard Lilford, CLAHRC WM Director


  1. Lilford RJ. Effects of Salt in Diet. NIHR CLAHRC West Midlands News Blog. 17 October 2014.
  2. Lilford RJ. On Diet Again. NIHR CLAHRC West Midlands News Blog. 23 October 2015.
  3. Lilford RJ. How Much Sugar is Too Much? NIHR CLAHRC West Midlands News Blog. 25 September 2015.
  4. Lilford RJ. Two Provocative Papers on Diet and Health. NIHR CLAHRC West Midlands News Blog. 12 December 2014.
  5. Etemadi A, Sinha R, Ward MH, Graubard BI, Inoue-Choi M, Dawsey SM, Abnet CC. Mortality from different causes associated with meat, heme iron, nitrates, and nitrites in the NIH-AARP Diet and Health Study: population based cohort study. BMJ. 2017; 357: j1957.
  6. Lebwohl B, Cao Y, Zong G, Hu FB, Green PHR, Neugut AI, Rimm EB, Sampson L, Dougherty LW, Giovannucci E, Willett WC, Sun Q, Chan AT. Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: prospective cohort study. BMJ. 2017; 357: j1892.
  7. Rai SK, Fung TT. Lu N, Keller SF, Curhan GC, Choi HK. The Dietary Approaches to Stop Hypertension (DASH) diet, Western diet and risk of gout in men: prospective cohort study. BMJ. 2017; 357: j1794.
  8. Godlee F. Red meat: another inconvenient truth. BMJ. 2017; 357: j2278.

Exercise and Energy Expenditure: Not What You Think?

Each week I burn up to 1,500 kcals in my two hours of intense ‘spinning’. So you might have thought (like me) that I could indulge in 1,500 kcals worth of extra puddings. Well you (like me) would have thought wrong, at least according to careful animal and human studies described by Pontzer in this month’s Scientific American.[1] Apparently, short of being an absolute coach potato or an extreme sportsman like Mark Spitz, the rest of us burn the same number of Calories per day, adjusted for mass, irrespective of how much we exercise. Apparently the body compensates for activity by consuming less Calories at rest. Says Pontzer, “exercise to stay healthy, but restrict Calories to control weight

Richard Lilford, CLAHRC WM Director


  1. Pontzer H. The Exercise Paradox. Scientific American. February 2017.


More on Fats and Their Effect on Cholesterol, Heart Disease, and Death

The accumulating evidence on the lack of association between eating saturated fat and heart disease has featured in previous posts.[1] [2] An intriguing re-analysis of an RCT carried out in nursing homes and hospitals for mental illness has recently been published in the BMJ.[3] In this trial saturated fats were replaced in the diet by polyunsaturated fats. The now familiar story was confirmed; yes, the polyunsaturated fat is associated with lower cholesterol levels, but no, there was no hint of a decrease in heart attack or all-cause mortality in the low fat group. The authors then carried out a systematic review, finding five RCTs examining the same hypothesis. They provided strikingly similar results; the meta-analysis corroborated the nursing home study. One intriguing point made in an accompanying editorial [4] is that the climate was so heavily slanted towards the fat and cholesterol hypothesis that the trial, which ended in 1973, was not published until 1989. But opinion has eventually caught up with the evidence and US dietary guidelines have finally removed dietary cholesterol and fat from the list of foods that should be avoided.[5] But note this point – the fact that saturated fats are no worse than polyunsaturated fats does not mean that there are not yet better sources of calories. And, yes, plants are better than meat, butter, etc. They are boring to eat, of course, but they are probably the best source for most of our calories.

— Richard Lilford, CLAHRC WM Director


  1. Lilford R. More on Diet. NIHR CLAHRC WM News Blog. 14 August 2015.
  2. Lilford R. On Diet Again. NIHR CLAHRC WM News Blog. 23 October 2015.
  3. Ramsden CE, Zamora D, Majchrzak-Hong S, et al. Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73). BMJ. 2016; 353: i246.
  4. Veerman JL. Dietary fats: a new look at old data challenges established wisdom. 2016; 352: i1512.
  5. US Department of Health and Humans Services and US Department of Agriculture. 2015-2020 Dietary Guidelines for Americans. 8th Washington, D.C.: USDA, 2015



Golden Rice Controversy

Genetically modified rice – called ‘golden rice’ – can increase yields and, since it produces beta-carotene, can prevent the sequelae of vitamin A deficiency that is common in those with a predominantly rice-based diet. For an interesting article on the controversy over use of this GM crop in Bangladesh, and its potential costs-benefit, please read Uttam Deb’s article from the Copenhagen Consensus Center.[1]

— Richard Lilford, CLAHRC WM Director


  1. Deb U. Returns to Golden Rice Research in Bangladesh: An Ex-ante Analysis. Bangladesh Priorities, Copenhagen Consensus Center, 2016.


Caution should be Exercised when Synthesising Evidence for Policy

Policy should be formulated from all the available evidence. For this reason systematic reviews and meta-analyses are undertaken. However, they are often not conclusive. Indeed, there have been notable articles published in the BMJ over the last two years which are critical of the evidence or conclusions of reviews that have been conducted to inform important contemporary public health decisions.

A key theme that often emerges from articles critical of reviews is that only evidence from randomised controlled trials (RCTs) is strong enough to support policy decisions. For example, Teicholz [1] claimed that a number of important RCTs were ignored by a recent report explaining changes in dietary guidance in the US. This claim has since been refuted by a large number of prominent researchers.[2] Kmietowicz [3] argued that there were flaws in a meta-analysis of observational patient data that supported the stockpiling of anti-flu medication for pandemic influenza, casting doubt on the decision to stockpile. An upcoming analysis of clinical trial data was instead alluded to, despite these trials only examining seasonal flu. Recently, McKee and Capewell,[4] and later Gornall,[5] criticised the evidence underpinning a comprehensive review from Public Health England [6] on the relative harms of e-cigarettes. They noted that it “included only two randomised controlled trials” and that there were methodological weaknesses and potential conflicts of interest in the other available evidence. McKee and Capewell make the claim that “the burden of proof that it is not harmful falls on those taking an action.” However, this is illogical because any policy choice, even doing nothing, can be considered an action and can cause harm. This claim therefore merely translates to saying that the policy chosen should be that best supported by the evidence of its overall effects.

Public health decisions should be made on the basis of all the currently available evidence. What then are reasons one might write off a piece of evidence entirely? One might object to the conclusions reached from the evidence on an ideological basis, or one might view the evidence as useless. In the latter case, this opinion could be reached by taking a rigid interpretation of the ‘hierarchy of evidence’. RCTs may be the only way of knowing for sure what the effects are, but this is not tantamount to concluding that other evidence should be rejected. RCTs are often, correctly in our view, regarded as an antidote to ideology. However, it is important not to let matters get out of hand so that RCTs themselves become the ideology.

In a recent paper, Walach and Loef,[7] argue that the hierarchy of evidence model, which places RCTs at the top of a hierarchy of study designs, is based on false assumptions. They argue that this model only represents degrees of internal validity. They go on to argue that as internal validity increases, external validity decreases. We don’t strictly agree: there is no necessary decoupling between internal and external validity. However we do agree that in many cases, by virtue of the study designs, RCTs may provide greater internal validity and other designs greater external validity. Then how could we know, in the case of a discrepancy between RCTs and observational studies, which results to rely on? The answer is that one would have to look outside the studies and piece together a story, i.e. a theory, and not ignore the observational evidence as recognised by Bradford-Hill’s famous criteria.

The case of chorion villous sampling, a test to detect foetal genetic abnormalities, serves as a good example of how different forms of evidence can provide different insights and be synthesised. Observational studies found evidence that chorion villous sampling increased the risk of transverse limb deformities, which was not detected in any of the RCTs at the time. To make sense of the evidence and to understand whether the findings from the observational evidence were a result of random variation in the population or perhaps poor study design, knowledge of developmental biology, teratology, and epidemiology were required. It turned out that the level of the transverse abnormality – fingers, hands, forearm, or upper arm – corresponded to the embryonic age at which the sampling was conducted and also to the development of the limb at that point. This finding enabled a cause and effect conclusion to be drawn that explained all the evidence and resulted in recommendations for safer practice.[8] [9]

Knowledge gained from the scientific process can inform us of the possible consequences of different policy choices. The desirability of these actions or their consequences can be then assessed in a normative or political framework. The challenge for the scientist is the understanding and synthesising of the available evidence independently of their ideological stance. There often remains great uncertainty about the consequences of different policies. In some cases, such as with electronic cigarettes, there may be reason to maintain the current policy if, by doing so, the likelihood of collecting further and better evidence is enhanced. However, in other cases, like stockpiling for pandemic influenza, such evidence depends on there being a pandemic and by then it is too late. Accepting only RCT evidence or adopting an ideological stance in reporting may distort what is reported to both key policy decision makers and individuals wishing to make an informed choice. It may even be potentially harmful.

— Richard Lilford, CLAHRC WM Director
— Sam Watson, Research Fellow


  1. Teicholz N. The scientific report guiding the US dietary guidelines: is it scientific? BMJ. 2015; 351: h4962.
  2. Centre for Science in the Public Interest. Letter Requesting BMJ to Retract “Investigation”. Nov 5 2015.
  3. Kmietowicz Z. Study claiming Tamiflu saved lives was based on “flawed” analysis. BMJ. 2014; 348: g2228.
  4. McKee M, Capewell S. Evidence about electronic cigarettes: a foundation built on rock or sand? BMJ. 2015; 351: h4863.
  5. Gornall J. Public Health England’s troubled trail. BMJ 2015;315:h5826
  6. McNeill A, Brose LS, Valder R, et al. E-cigarettes: an evidence update: a report commissioned by Public Health England. London: Public Health England, 2015.
  7. Walach H & Loef M. Using a matrix-analytical approach to synthesizing evidence solved incompatability problem in the hierarchy of evidence. J Clin Epidemiol.  2015; 68(11): 1251-1260
  8. Olney RS. Congenital limb reduction defects: clues from developmental biology, teratology and epidemiology. Paediatr Perinat Epidemiol. 1998; 12: 358–9.
  9. Mowatt G, Bower DJ, Brebner JA, et al. When and how to assess fast-changing technologies: a comparative study of medical applications of four generic technologies. Health Technol Assess. 1996; 1: 1–149.