Stop Taking Those Supplements: Just Stop

There is a strong natural human instinct to take precautions to delay the death the lies ahead for us all. So strong is this instinct that we are predisposed to believe in all sorts of measures with a superficial, but fundamentally facile, theoretical basis. Food supplements are such a measure.

So yet another study shows that they do no good, and in some cases they likely increase the very risks that they are designed to prevent.[1] A recent article by Chen and colleagues follows up a cohort of over 30,000 adults who completed a nutrition questionnaire yearly for six years. A healthy diet was associated with lowered cancer mortality risk, but supplements were not, and could even raise risks. With respect to minerals, NEVER take supplements, because it is the balance between metal couples (sodium/potassium; magnesium/calcium; copper/zinc) that is important. So it is not surprising that calcium supplements were harmful in the above study.

Studies of this type are subject to personal and recall bias but, in my opinion, these work against the findings. People who take care of their health usually have better outcomes than people at large, and recall bias is augmented if the bad endpoint materialises, whereas the overall results in this study were null.

— Richard Lilford, CLAHRC WM Director

Reference:

1. Chen F, Du M, Blumberg JB, et al. Association Among Dietary Supplement Use, Nutrient Intake, and Mortality Among U.S. Adults. Ann Intern Med. 2019; 170: 604-13.

Can Diet Help Maintain Brain Health?

A recent study in the journal of Neurology looked at the long-term effects high fruit and vegetable intake had on a person’s cognitive function.[1] The authors were able to research and follow-up 27,842 US men over a 26 year period. These men were middle-aged (mean age of 51 years) and were or had been health professionals.

Every four years, from 1986 to 2002, they completed questionnaires looking at their eating habits, and then completed subjective cognitive function questionnaires in 2008 and 2012. Logistic regression of the data found significant individual associations between higher intakes of vegetables (around six servings a day compared to two), fruits (around three servings a day compared to half) and fruit juice (once a day compared to less than once a month) and lower odds of moderate or poor subjective cognitive function. These associations remained significant after adjusting for non-dietary factors and total energy intake, though adjusting for dietary factors weakened the association with fruit intake. Daily consumption of orange juice (compared to less than one serving per month) was associated with much lower odds of poor subjective cognitive function, with an adjusted odds ratio of 0.53 (95% CI 0.43-0.67). Meanwhile the adjusted odds ratios for vegetables were 0.83 (05% CI 0.76-0.92) for moderate, and 0.66 (0.55-0.80) for poor subjective cognitive function. The authors also found that high intake of fruit and vegetables at the start of the study period was associated with a lower risk of poor subjective cognitive function at the end of the study. Although the study does not prove a causal link, the fact that the association lasted the length of the study support the idea that vegetable and fruit consumption may help avert memory loss.

— Peter Chilton, Research Fellow

Reference:

1. Yuan C, Fondell E, Bhushan A, Ascherio A, Okereke OI, Grodstein F, Willett WC. Long-term intake of vegetables and fruits and subjective cognitive function in US men. Neurology. 2018.

Changes in Mealtimes Leading to Eating Less

People have long looked for a method of dieting that is effective and easy to undertake. A recent pilot study in the Journal of Nutritional Sciences may offer a new alternative.[1] For ten weeks participants were required to both delay their usual breakfast time and bring forward their evening meal time by an hour and a half – there were no other restrictions on what food they could consume, or what exercises they needed to do. When compared to a control group they found that the participants in the intervention group reduced their daily energy intake (p=0.019), with an associated reduction in adipose levels (p=0.047). Further, there was also a significant difference in fasting glucose levels, though the authors note that this was mainly due to an increase in control participants compared to baseline. Questionnaire results suggest that the reduction in energy intake may have been due to less time for snacking, and/or still feeling full from the previous meal. Unfortunately the majority of participants found that the restrictions were too severe, impacting on their social and family life, and did not believe they could continue past the end of the study.

Although this was only a very small study of 13 participants it shows a potential opportunity for future research.

— Peter Chilton, Research Fellow

Reference:

1. Antoni R, Robertson TM, Robertson MD, Johnston JD. A pilot feasibility study exploring the effects of a moderate time-restricted feeding intervention on energy intake, adiposity and metabolic physiology in free-living human subjects. J Nutri Sci. 2018;7:e22.

Gluten Sensitivity but no Antibodies?

Consider the case of my good friend who developed gluten sensitivity in midlife. Subsequently he went on a gluten-free diet – his wife found this a terrible nuisance. So she surreptitiously re-introduced wheat to his diet. Within no time my friend complained and that he had been wrong, his symptoms had reoccurred despite no apparent exposure to wheat. He was disappointed with his wife when she had to confess to her clandestine challenge to his physiology. But I think she behaved like a true scientist!

The single case represented by my friend has been repeated on a larger-scale many times. The results have been the same; many people with gluten sensitivity manifest symptoms when challenged in blind studies.[1] Furthermore, unlike many types of putative psychosomatic illness, people with gluten sensitivity do not manifest different responses on psychological testing for depression or anxiety compared with those of the general population.

So what is the cause of this somatopsychic condition? It turns out that there are two main theories each with some evidence in their favour.[2] The theory that I prefer is called FODMAPs, based on the idea that wheat is a potent source of fermentable, short chain carbohydrates. These carbohydrates are poorly absorbed and thus ferment in the gut causing the typical symptoms of bloating, distention and discomfort. The alternative theory is that wheat, perhaps in the presence of certain alterations in the microbiome, causes an inflammatory reaction in the liver that is associated with symptoms.

It will be important to discern the cause, since treatment of excessive fermentation would consist of a more general reduction of foods containing large proportions of fermentable carbohydrates.

— Richard Lilford, CLAHRC WM Director

References:

1. Skodje GI, Sarna VK, Minelle IH, Rolfsen KL, Muir JG, Gibson PR, Veierød MB, Henriksen C, Lundin KEA. Fructan, Rather Than Gluten, Induces Symptoms in Patients With Self-Reported Non-Celiac Gluten Sensitivity. Gastroenterol. 2018; 154: 529-39.
2. Servick K. The war on gluten. Science. 2018; 360: 848-51.

Food Deserts: a Problem of Supply or Demand?

That poor people have a less healthy diet than rich people is not in doubt. That poor people have worse health because they have less healthy diets is also not in doubt. That poor people have less access to healthy food than rich people is, again, not in doubt. This series of observations has led to a predominant narrative: that the poor are denied the healthy foods that they would choose, where it only that they had equitable access to healthy options.

This does not follow, any more than the argument that low access to contraception is causative of high birth-rates. It is quite feasible that low demand is the cause of both low access and the corresponding outcomes, both in the case of the pill and low access to healthy food.

Allcott and colleagues addressed this issue with respect to diet and health.[1] They examined the possibility that observed differences in supply of healthy foods are a response to differences in the demand for those foods in different neighbourhoods. The authors examined this through a rich array of data sets, one of which covered nearly half of all US grocery purchases. They were able to examine how people of different socioeconomic group behave when supermarkets are established in new locations, or when people move into, or out of, food ‘deserts’. Effectively they treat these geographic changes as instrumental variables.

When they examined the effect of entry of a new supermarket in a given locality, they find that local supermarket entry does not materially increase healthy eating. Then they examined the converse – movement of a household to an environment where more healthy food is available. Again, behaviour does not converge towards the general eating pattern in the new location.

Could this be because the supermarkets charge more for healthy products in poor neighbourhoods than they do in rich neighbourhoods? The authors examined this possibility and were able to exclude it. What they found is that poorer households are willing to pay much less than wealthier households for healthy food. As a result they are provided with less healthy food.

The results are broadly consistent with studies on education and food preferences. Food deserts exist, but they are not the result of supply-side failure. Rather they reflect the role of culture and tastes in the United States, as they have been shown to do in so many other places. The effects observed in the study did not change over many years. Policy initiatives that simplistically target food deserts are thus unlikely to succeed.

— Richard Lilford, CLAHRC WM Director

Reference:

1. Allcott H, Diamond R, Dubé J-P. The Geography of Poverty and Nutrition: Food Deserts and Food Choices Across the United States. NBER Working Paper No. 24094. 2018.

Dieting Does a Lot of Good, Even If You Don’t Lose Much Weight

Well this paper gave me pause for thought.[1] I have always been rather nihilistic about dieting. The effect sizes in terms of actual weight loss seem nugatory and transient – a couple of kilograms after three years would be fairly typical. Well I was prompted to change my mind as a result of a recent meta-analysis of 54 RCTs of diet vs. no-diet. Most of the diets stressed saturated fat reduction as part of the diet, and most advocated exercise as well as a diet (although in only half of these trials were patients referred to a specific exercise programme). As I would have predicted weight loss was small in the intervention group vs. control – 3.4kg at one year, and 2.5kg at two years. Despite these small effect sizes, all-cause mortality was reduced by 18% (0.7-0.95) in the diet group. This finding held good, even when only the 34 best quality RCTs were retained in the analysis. There was a borderline significant reduction in cancer death in the diet groups among the eight trails that recorded this outcome. In an earlier study of abnormal liver function tests [2] we noted improvement in fatty livers in people who lost only small amounts of weight. My conclusion – it is worth persuading people to lose weight through diet and exercise. Even if the effects on weight are small they are not, after all, nugatory.

— Richard Lilford, CLAHRC WM Director

References:

1. Ma C, Avenell A, Bolland M, Hudson J, Stewart F, Robertson C, Sharma P, Fraser C, MacLennan G. Effects of weight loss interventions for adults who are obese on mortality, cardiovascular disease, and cancer: systematic review and meta-analysis. 2017; 359: j4849.
2. Lilford RJ, Bentham L, Girling A, Litchfield I, Lancashire R, Armstrong D, Jones R, Marteau T, Neuberger J, Gill P, Cramb R, Olliff S, Arnold D, Khan K, Armstrong MJ, Houlihan DD, Newsome PN, Chilton PJ, Moons K, Altman D. Birmingham and Lambeth Liver Evaluation Testing Strategies (BALLETS): a prospective cohort study. Health Technol Assess. 2013; 17(28):1-307.

Corroboration of Previous Reports on Vitamin D and on Coffee

In recent News Blogs we have provided evidence that vitamin D and calcium are useless in preventing osteoporotic fractures in elderly people with no obvious risk factors.[1] [2] This is now powerfully corroborated in a paper in JAMA by Zhao, et al.,[3] who carried out a systematic review and meta-analysis involving over 50,000 participants. They found absolutely no beneficial or harmful effects of either vitamin D or calcium or a combination of the two compared to placebo in reducing the risk of either vertebral hip or other non-vertebral fractures. The absolute risk difference was zero with an upper confidence limit of 0.01. Hopefully this puts the matter to bed once and forever.

Likewise a recent umbrella review in the BMJ [4] corroborated previous news blogs on the generally health promoting effects of coffee.[5] It would appear that these benefits are also seen in equal measure with de-caffeinated coffee, suggesting that it is the other components of coffee that benefit health.

— Richard Lilford, CLAHRC WM Director

References:

1. Lilford RJ. Effects of Vitamin D Supplements. NIHR CLAHRC West Midlands News Blog. 24 March 2017.
2. Lilford RJ. Yet Another Null Result on Vitamin D and Calcium Supplementation in Older Women. NIHR CLAHRC West Midlands News Blog. 5 May 2017.
3. Zhao J-G, Zeng X-T, Wang J, et al. Association Between Calcium or Vitamin D Supplementation and Fracture Incidence in Community-Dwelling Older Adults: A Systematic Review and Meta-analysis. JAMA. 2017; 318(24): 2466-82.
4. Poole R, Kennedy OJ, Roderick P, Fallowfield JA, Hayes PC, Parkes J. Coffee consumption and health: umbrella review of meta-analyses of multiple health outcomes. BMJ. 2017; 359: j5024.
5. Lilford RJ. Should You Keep Drinking Coffee? NIHR CLAHRC West Midlands News Blog. 1 September 2017.

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

References:

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

Reference:

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

References:

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.