Longevity Briefs: Can Early Life Sugar Restriction Slow Ageing?

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

How much influence do conditions in very early life have on long term health? You may have heard of the Dutch famine of 1944-1945, which occurred over winter in the Netherlands when the Nazis cut off food supplies to the western part of the country. Though a tragic event in which many died, this and other similar events have also provided a unique research opportunity, as it essentially resulted in an accidental clinical trial. Scientists were able to compare people born during the famine to those born just after it, and found that being exposed to famine during the first 1000 days or so after conception (especially during early gestation) had wide ranging health impacts, from poorer kidney function to increased risk of anxiety and depression later in life. This provided convincing evidence that even relatively brief exposure to nutrient deficiency could have significant long-lasting health impacts.

Over time, scientists have come to understand that many environmental factors, such as obesity during pregnancy or exposure to cigarette smoke in early life, can influence health in later life. In this study, researchers ask whether something as subtle as early life exposure to sugar can influence late life health. Conducting an observational study to answer this question would be tricky as those exposed to more sugar in early life tend to continue that exposure, making the effects of early life sugar impossible to isolate. To avoid this problem, researchers needed to find some form of temporary, externally imposed sugar restriction. This came in the form of post World War II sugar rationing in the UK.

The discovery:

Researchers looked at data from 64,809 participants from the UK biobank (a large anonymised health database) who were born up to around 2 years before or 2.5 years after the moment sugar rationing ended in September of 1953. Participants were then grouped according to how much sugar rationing they were exposed to: no rationing, rationing in utero, or rationing in utero plus up to 6,12,18 or 24 months of rationing post-birth. Participants had a mean (average) age of 54.6 at the start of the study and were followed up for 13-17 years. Researchers estimated that sugar intake rose by around 50% after rationing ended, while fat intake increased modestly, though overall calorie intake would only have been around 5% higher.

Researchers found that those in the rationed groups earned slightly less on average, were less likely to smoke and consumed less sugar as adults, so these factors had to be controlled for. After adjustments were made, researchers then looked at whether there was a relationship between sugar rationing and the incidence of 83 ‘hallmark-related diseases’, meaning diseases known to be driven or influenced by the hallmarks of ageing. They found that sugar rationing during the first ~1000 days since conception was associated with a statistically significant 5-10% reduced risk of hallmark-related diseases, regardless of ethnicity. Some of the most notable associations included an 18% reduction in breast cancer, a 25% reduction in viral infections and a 21% reduction in type II diabetes. Participants in the rationed group also had a 19% lower chance of dying from any cause during the follow-up period compared to the non-rationed group.

There appeared to be a dose-response relationship between duration of rationing and reduced disease risk – that is to say that more time spent during the sugar rationing period was associated with a greater reduction in disease risk. Researchers also estimated participants’ biological age using epigenetic clocks (algorithms that estimate ‘true biological age’ based on alterations to the DNA molecule) and found that rationed participants’ scores were around 1 year lower than non-rationed participants, suggesting that they could be ageing at a slower pace. Finally, researchers measured the levels of proteins in the blood and found differences in some ageing-associated signalling pathways that would be consistent with slower ageing in the rationed group.

The implications:

This is not the first study to suggest that early life sugar exposure has long-term health implications, but how? Exposure to the blood sugar-lowering hormone insulin in both the womb and in breast milk may shape metabolic set-points – that is to say what blood sugar level, weight and so on the body attempts to maintain. There is also some evidence to suggest that infants exposed to more sugar early on develop a greater preference for sweet foods that then influences their diet throughout life. This is supported by the finding in this study that the rationed group had lower sugar intake as adults, though the difference was relatively small.

During rationing, adults were limited to less than 40g of sugar per day, while infants under two years old weren’t allowed any added sugar at all. This is similar to the current WHO guidelines of restricting free sugar intake to below 10% of daily calorie consumption (preferably down to 5%) and complete avoidance before the age of 2.