Low carbohydrate diets: mortality and diabetes long term data

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    In this video, Dr. Seheult of MedCram discusses mortality and diabetes long term data from low carbohydrate diets.

    When did low carb diets start?

    Low carbohydrate diets started out in the 1950’s as possible treatment for childhood epilepsy. These diets have also been looked at for their short term benefits on weight loss.  There are carbohydrates, proteins and fats in a normal diet. There are three popular low carb diets including the Atkins induction phase diet, classic ketogenic diet 4:1 ( 4 grams fat to 1 gram protein) and medium chain triglyceride ketogenic diet. The photos shown in the video regarding these diets are an oversimplification.

    How do carbs affect the body?

    If you just look at carbohydrates, the carbohydrates that come from processed foods and refined sugars  have an effect on the body that is completely different compared to the same amount of carbohydrates that come from complex carbohydrates such as fruit. Fruit is complexed with polyphenols. Carbohydrates from fruit juices have different effects on the body than carbohydrates from whole fruits.

    What have prior studies shown?

    There is a large movement to look at low carbohydrate diets. There was a paper published 10 years ago that discussed low carbohydrate diets (LCD) and all-cause mortality: a systematic review and meta-analysis of observational studies.  It was known 10 years ago that a low-carbohydrate diet and its combination with high-protein diets are effective in weight loss. These diets in the short term ameliorate the risk factors of cardiovascular disease, but long-term health benefits and risks remain controversial. The researchers noted that low-carbohydrate diets tend to result in reduced intake of fiber and fruits and increased intake of protein from animal sources, cholesterol and fats.  The study took a comparison between a low-carbohydrate score and a low carbohydrate/high-protein score and looked at cardiovascular risks and risk of death. In the low carbohydrate score,  they found an increased risk of all-cause mortality in the low-carbohydrate scores.  A similar finding was found in the low carbohydrate/high-protein scores. The conclusion of this paper on observational data was that low-carbohydrate diets were associated with a significantly higher risk of all-cause mortality, and they were not significantly associated with a risk of cardiovascular disease mortality and incidence. However, it was noted this was a limited study as it was observational and it was needed to have large-scale trials on the complex interaction between low carb diet and long-term outcomes are needed.

    Can you do a randomized trial involving diet?

    The point of this is that you will never be able to do a randomized double blinded placebo controlled low carb diet study. So the next best study type is a dose response relationship as seen in other epidemiological studies. If you can show in a study (without doing a randomized, blinded study) that prospectively in a cohort of people, that increased exposure to a risk causes an increased determinate of an outcome, then that dose response curve is highly suggestive of causation. This is how we made this determination from other substances such as smoking and asbestos where you can’t ethically and practically do a randomized controlled study. This article from 1981 in the Royal Society Publishing  discussed this. This is the way you can show in large scale studies that in a dose response curve you can show causation.

    What does the latest data on low carb diets and diabetes show?

    Recently a new abstract from 2022, that is on its way to publication, was discussed at the American Heart Association meeting. It looked at a large cohort from the Nurses’ Health Study (NHS), NHSII, and Health Professionals follow-up study.  It took 203,451 men and women who did not have diabetes, cancer, or cardiovascular disease at baseline and followed them for over thirty years.  They asked them specific questions about what they ate. They checked in every four years. For low carbohydrate diets they came up with a score and divided them into five groups. The score reflected how intense the low carbohydrate diet was. Those individuals who were in the first quintile were the weakest in a low carbohydrate amount, they were given a reference number of 1. Then the rest of the groups were looked at to see as the dose of the low carbohydrate diet went up what was the risk for diabetes. They are trying to apply a dose response curve to a large epidemiological study.  They looked at over 5 million person years of follow -up. They found 19,675 type II diabetes. They found that the people with the higher overall low carbohydrate diet score were associated with a higher type 2 diabetes risk in a dose-response manner. In this study, it was a prospective observational study and generally speaking you can still have confounders. The difference here is that a dose response curve was done and this is the same type of evidence we would use for smoking and cancer and asbestos and mesothelioma. The study had 5 different types of dietary patterns: overall low carbohydrate diet (LCD) score, animal based LCD score, vegetable based LCD score, unhealthy LCD score (animal+ decreased whole grain), healthy LCD score (vegetable + decreased refined carbohydrates). In each of these there was a multivariable adjustment for age, ethnicity, smoking status, BMI, alcohol, multivitamin use, physical activity, total energy intake, family history of diabetes, hormone replacement therapy, and OCP use. They found that as the doses of a low carbohydrate score increased that there was an increase of up to 28% risk for developing diabetes and that this was statistically significant. In the unhealthy LCD score of animal and decreased whole grains that same risk went up 39% in the highest dose response.

    The study looked at another variation by looking at a LCD but the sources of carbohydrates came from plants rather than animal protein.  In these there was noted to be a reduction in the risk up to 6%. In the LCD vegetable protein with decreased refined carbohydrates (ie soda, candies), it showed a reduction of up to 15% reduction in risk of getting type 2 diabetes. This just shows that not all low carbohydrate diets are the same and there could be up to a 54% difference in the risk of diabetes depending on the type of low carbohydrate diet you are on.  

    What does the latest data on low carb diets and mortality show?

    There was another paper that was published in February 2023 that discussed LCD scores and mortality among adults with incident type 2 diabetes.  Here they are looking at individuals that already have diabetes and asking if they are going on a LCD. This study took 10,101 persons with a contribution of 139,407 person years during follow-up and they documented about 4595 deaths of which 1389 cases were attributed to cardiovascular disease and 881 to cancer. These participants were identified in the Nurses’ Health Study and the Health Professional Follow-up Study. They took an overall total low carbohydrate diet score and calculated it based on the percentage of energy as total carbohydrates. Now in this study, they weren’t looking for chances of diabetes (as the participants already had diabetes), they were looking at chances of mortality. The study found that all-cause mortality was decreased with a LCD overall; however, as the types of LCD were analyzed it was found that an animal LCD did not show any difference in mortality but the vegetable LCD showed a 24% reduction in mortality and the healthy LCD which eliminated refined sugars also had a 22% reduction in mortality. The unhealthy LCD which eliminated whole grains had a slight increase in mortality.

    Dr. Seheult found this to be interesting. There isn’t a lot of discussion in LCD as to where the proteins are coming from but these studies suggest there is a large difference in the types of carbohydrates.

    Is fruit good or bad in low carb diets?

    There was a study on fresh fruit consumption in relation to incident diabetes and diabetic vascular complications. It was a 7 year prospective study and the study found that as the amount of fruit consumption goes up that there was a reduction in the incidence of diabetes and all-cause mortality. This was probably due to the fact whole fruits and whole grains have things packaged in them aside from sugars that provide benefits to the body and eliminating them can lead to detriments to the body. 

    What about animal proteins in low carb diets?

    In a prior MedCram video on Meat, dairy and disease, it was found that there is a specific sialic acid found on red meat (regardless of how it was raised) called Neu5Gc. Human beings do not have this sialic acid. When humans eat animals with this sialic acid, it gets incorporated into human cells; however, the immune system recognizes it as foreign and may cause some mild underlying inflammation to be ongoing by causing Neu5Gc antibodies. It was felt that this may be why we see more vascular inflammation in people who have red meat. 

    However, more research is needed, but it would be prudent to evaluate your diet to see if you think you need any changes based on your current health. 



    Low-Carbohydrate Diets and All-Cause Mortality: A Systematic Review and Meta-Analysis of Observational Studies (PLoS One) | https://www.ncbi.nlm.nih.gov/pmc/arti…

    Low-Carbohydrate Diet Scores and Mortality Among Adults With Incident Type 2 Diabetes (ADA) | https://diabetesjournals.org/care/art…

    Fresh fruit consumption in relation to incident diabetes and diabetic vascular complications: A 7-y prospective study of 0.5 million Chinese adults (PLoS) | https://www.ncbi.nlm.nih.gov/pmc/arti…

    New Research: Sialic Acids May Contribute to Inflammation & Disease (MedCram) |    • New Research: Sia…  

    Association between Neu5Gc carbohydrate and serum antibodies against it provides the molecular link to cancer: French NutriNet-Santé study (BMC) | https://www.ncbi.nlm.nih.gov/pmc/arti…


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