Hi, it’s Dr Brukner, Defeat Diabetes founder.
I thought I would share my favourite research articles of 2022. I read a lot of papers, but only a small percentage of everything out there, so I don’t pretend this is comprehensive. The research articles are mainly low carb with an emphasis on type 2 diabetes.
Why have I chosen these articles? Various reasons. Good science, excellent summaries, thought-provoking policy suggestions and important topics. Let me know the good ones I have missed.
At the end, I give you my 2022 best Books, Podcasts and Blog of the Year.
Low carb and type 2 diabetes
Low carb and glycaemic control
Firstly an RCT – in a Danish open-label randomized controlled trial, patients with T2D were randomized 2:1 to either a non-calorie-restricted LCD with a maximum of 20 E% from carbohydrates (n = 49) or a control diet with 50-60 E from carbohydrates (n = 22) for 6 months. The LCD reduced HbA1c after 3 months by an average of 8.9 mmol/mol, which was maintained after 6 months (-7.5 mmol/mol) compared with the control diet. The LCD also reduced weight by 4 kg, BMI by 1.4 kg/m2, and waist circumference by 5 cm) compared with the control diet – all statistically significant results.
Diversa Health and CSIRO
Grant Brinkworth and his colleagues at the CSIRO in Australia examined the efficacy of the Diversa Health program, a low carbohydrate diet program delivered by health care professionals. 511 individuals participated for an average of 218 days. The average weight loss was 6 kg, and in those with an HbA1c of >6.5%, 90% experienced an HbA1c reduction, and 54% achieved a final HbA1c < 6.5%. Sadly, shortly after these results were published, the Diversa program closed due to a lack of funding.
Keto diets and type 2 diabetes
Researchers from the University of Otago in New Zealand conducted a systematic review of randomized controlled trials of at least 6 months duration comparing efficacy and safety of VLC/KDs (≤50 g carbohydrate or ≤10% total energy from carbohydrate per day) with a control diet (carbohydrate above the VLC/KD threshold) in adults with pre-diabetes or T2D. Eight studies met the inclusion criteria involving 606 participants. There was an estimated difference in HbA1c of 0.65% in the two studies which reported summaries pooled statistically significant difference between randomized arms after 12 months and 0.01% in the four studies that reported HbA1c change from baseline.
Carb restriction and type 2 diabetes
Jayedi and colleagues in Iran performed a systematic review to evaluate the dose-dependent effect of carbohydrate restriction inpatients with type 2 diabetes. Fifty trials with 4291 patients were identified. At 6 months, compared with a carbohydrate intake between 55%–65% and through a maximum reduction down to 10%, each 10% reduction in carbohydrate intake reduced HbA1c an average of 0.20%; fasting plasma glucose (FPG) 0.34 mmol/L, and body weight 1.44 kg. There were also reductions in total cholesterol, LDL cholesterol, TG, and systolic blood pressure (SBP). Levels of HbA1c, FPG, body weight, TG, and SBP decreased linearly with the decrease in carbohydrate intake from 65% to 10%.
Lower diagnostic thresholds
There is ample evidence that HbA1c and fasting glucose levels in the “pre-diabetic” range are not “normal” and in fact are indicative of early metabolic disease. This timely article by Stanley Schwartz and colleagues suggests lowering the diagnostic thresholds.
The subject of diabetes remission/reversal has been a hot topic this year and this is a good review of the various ways in which diabetes remission can occur – surgery, medications, low energy and low carb diets, and exercise. A pretty balanced approach.
Very little research has been done into the effect of low carb diets on those with pre-diabetes.
Pre-diabetes and mortality
An umbrella review aimed to provide a systematic overview of the available evidence from meta-analyses of prospective observational studies on the associations between pre-diabetes and incident diabetes-related complications in adults to evaluate their strength and certainty. 95 meta-analyses from 16 publications were identified. In the general population, pre-diabetes was associated with a 6–101% increased risk for all-cause mortality and the incidence of cardiovascular outcomes, CHD, stroke, heart failure, atrial fibrillation and chronic kidney disease, as well as total cancer, total liver cancer, hepatocellular carcinoma, breast cancer and all-cause dementia with moderate certainty of evidence. No associations between pre-diabetes and incident depressive symptoms and cognitive impairment were observed (with low or very low certainty of evidence).
HbA1c and type 2 diabetes
Dorans and colleagues from New Orleans enrolled participants aged 40 to 70 years with untreated HbA1c of 6.0% to 6.9% and randomised them to a low carbohydrate diet intervention (target <40 net grams of carbohydrates during the first 3 months; <60 net grams for months 3 to 6) or usual diet. Compared with the usual diet group, the low-carbohydrate diet intervention group had significantly greater 6-month reductions in HbA1c (–0.23%), fasting plasma glucose (-10.3mg/dL), and body weight (–5.9 kg).
Type 2 diabetes: Genes v diet
Merino and colleagues examined the joint associations of genetic risk and diet quality with the incidence of type 2 diabetes. In 3 cohort studies involving 35,759 men and women in the US, they used novel polygenic scores for type 2 diabetes to systematically evaluate the presence of additive and multiplicative interactions between genetic risk and diet quality on the development of type 2 diabetes. They found that both low diet quality and increased overall or pathway-specific genetic risk were independently associated with higher risk of type 2 diabetes and documented that within any genetic risk category, high diet quality, as compared to low diet quality, was associated with a nearly 30% lower risk of type 2 diabetes. Further, they showed that the risk of type 2 diabetes attributed to the combination of increased genetic risk and low diet quality was similar to the sum of the risks associated with each factor alone.
Ketogenic diet and chronic disease
Zu et al from Shanghai published an extensive review summarising the experimental and/or clinical evidence of the efficacy and safety of the keto diet for different diseases, and discussed the possible mechanisms of action based on recent advances in understanding the influence of the KD at the cellular and molecular levels. They also tackled the challenges and future directions for the clinical implementation of the ketogenic diet in the treatment of a spectrum of diseases.
David Ludwig and an illustrious group of co-authors provide a comprehensive review of the two popular competing models of obesity causation: the energy balance model and the carbohydrate-insulin model. An excellent summary. I liked their conclusion – “public health action need not await resolution of this debate, as both models target processed carbohydrates as major drivers of obesity.”
As a follow up to that article David Ludwig proposed an integrated model of obesity pathogenesis that incorporates both pathways.
Fatty Liver (NAFLD)
In a nationally representative cohort (NHANES 2017-2018), Claypool et al assessed the relative prognostic importance of the seven key metabolic factors defined per the MAFLD criteria for steatosis and fibrosis outcomes. Insulin resistance and increased central obesity as measured by elevated waist circumference were the top two metabolic factors for steatosis independent of diabetes and weight.
Safety of fasting in type 2 diabetes
This open, single-centre, randomized, controlled trial, Intermittent fasting in subjects with insulin-treated type 2 diabetes mellitus (INTERFAST-2), was conducted at the University Hospital Graz, Graz, Austria, and included volunteers, aged between 18 and 75 years with insulin-treated type 2 diabetes, an HbA1c >53 mmol/mol (>7.0%), and a daily insulin dose of >0.3 IU/kg body wt. The IF group practiced IF 3 days a week, reducing their calories on these days by 75% (i.e., consuming only 25% of the recommended caloric intake). Ingestion was only allowed at breakfast and/or lunch to maintain an 18 hour period of fasting. On the remaining 4 days, participants of the IF group had no caloric or macronutrient restriction. They concluded that 3 days of non-consecutive IF per week over the duration of 12 weeks improved HbA1c, reduced body weight, and led to a total daily insulin dose reduction in people with insulin treated type 2 diabetes.
Efficacy of intermittent fasting in type 2 diabetes
This was a parallel-design, open-label, randomized controlled trial conducted in China which examined the effectiveness of IF in diabetes remission and potential remission durability. Participants with diabetes followed the Chinese Medical Nutrition Therapy (CMNT) , a dietary approach based on IF involving 5 fasting days followed by 10 days of reintroducing everyday food items. The CMNT diet contains daily foods such as wheat, barley, rice, rye, and oat, and features reduced glycemic loads, calories, and carbohydrates, as well as increased unsaturated fatty acids. They undertook a 3-month intervention period that included 6 cycles of 15 intervention days. In each cycle, the CMNT group was assigned a diet with 5 modified fasting days (∼840 kcal/day), during which patients were given CMNT kits at their regular meal schedule. After 3 months of the intervention, 50.0% (18/36) of participants in the CMNT group and 2.8% (1/36) in the control group ceased using antidiabetic medications. Moreover, 68.4% (13/19) of participants in the CMNT group and 2.8% (1/35) in the control group reduced their diabetes medication intake. Mean HbA1c levels in the intervention group reduced from 7.65% to 5.66%.
Ultra-processed foods (UPFs)
Ultra-processed foods and incidence of type 2 diabetes
UPFs are Public Enemy Number 1 at the moment – with good reason.
The association of UPFs and type 2 diabetes was examined in over 70,000 participants in the Lifelines cohort. During a median follow-up of 41 months, a 10% increment in UPF consumption was associated with a 25% higher risk of developing type 2 diabetes.
Ultra-processed foods and dementia
Huiping Li and colleagues investigated the associations between UPF and dementia incidence in the UK Biobank including 72,083 participants (55 years or older) who were free from dementia at baseline and provided at least two times 24 hour dietary assessments from the UK Biobank study. During a total of 717,333 person-years of follow-up (median 10.0 years), 518 participants developed dementia, of which 287 developed Alzheimer’s disease and 119 developed vascular dementia. In the fully adjusted model, consumption of UPF was associated with higher risk of dementia (hazard ratio (HR) for 10% increase in UPF: 1.25); Alzheimer’s disease (HR: 1.14; 95%) and vascular dementia (HR: 1.28), respectively. In addition, replacing 10% of UPF weight in diet with an equivalent proportion of unprocessed or minimally processed foods was estimated to be associated with a 19% lower risk of dementia.
UPFs and bowel disease
A Belgian group of researchers examined the available evidence on the possible role of UPFs and their components in the increasing incidence and prevalence of inflammatory bowel disease is reviewed.
UPFs and health
And finally, a French group published a comprehensive overview of the current data that highlights an association between ultra-processed food consumption and various chronic diseases, with a focus on epidemiological evidence and mechanistic insights involving the intestinal microbiota.
Global trends in artificial sweeteners
Some people think artificial sweeteners or non-nutritive sweeteners (NNS) are harmless and a good alternative to sugar. The evidence suggests otherwise.
Researchers from Deakin University in Australia aimed to assess trends in quantities of added sugars and NNS sold in packaged food and beverages worldwide and the association between these trends and the number of national policy actions across regions to reduce added sugar consumption. They found that per capita volumes of NNS from beverage sales increased globally (36%). Added sugars from beverage sales decreased in high-income countries (22%) but increased in upper and lower-middle-income countries (13-40%). Added sugars from packaged food sales increased globally (9%).
Artificial sweeteners and cardiovascular disease
In this large-scale, prospective cohort of French adults, artificial sweeteners (especially aspartame, acesulfame potassium, and sucralose) were associated with an increased risk of cardiovascular, cerebrovascular, and coronary heart diseases.
Sugary beverages and chronic disease
Malik and Hu reviewed the role of sugar-sweetened beverages in the global epidemics of obesity and chronic diseases. They examined the evidence linking SSBs to obesity, cardiometabolic outcomes and related cancers, as well as methods to grade the strength of nutritional research. They also discuss potential biological mechanisms by which constituent sugars can contribute to these outcomes.
Non-nutritive sweeteners and the microbiome
The effects of sweeteners on the microbiome is another much-discussed topic. In this study, researchers causally assessed non-nutritive sweeteners (NNS) impacts on humans and their microbiomes in a randomized-controlled trial encompassing 120 healthy adults, administered saccharin, sucralose, aspartame, and stevia sachets for 2 weeks in doses lower than the acceptable daily intake, compared with controls receiving sachet-contained vehicle glucose or no supplement. As groups, each administered NNS distinctly altered stool and oral microbiome and plasma metabolome, whereas saccharin and sucralose significantly impaired glycemic responses.
This systematic review included randomized controlled trials that investigated the effect of vitamins D, C, and E, magnesium, zinc, calcium, selenium, and omega-3 on at least one glycemic marker, including glycated hemoglobin (HbA1c), fasting blood sugar (FBS), homeostasis model assessment-estimated insulin resistance (HOMA-IR), HOMA-B, and insulin, in adults with type 2 diabetes. Analysis of 178 studies indicated that zinc, vitamin D, omega-3, vitamin C, and vitamin E effectively reduced HbA1c with low certainty. For the reduction of FBS, zinc, vitamin D, and vitamin C, and for HOMA-IR, vitamin D was effective with low certainty. None of the supplements was effective in the reduction of insulin and HOMA-B with low certainty. After excluding poor-quality studies, only vitamin D significantly reduced all of the markers. Consistently, when the analysis was restricted to studies with a duration of ≥12- weeks, vitamin D reduced HbA1c, FBS, and HOMA-IR.
Navale and colleagues from Adelaide used prospective data from the UK Biobank to examine the association between 25(OH)D concentrations with neuroimaging outcomes (N = 33,523) and the risk of dementia and stroke (N = 427,690; 3414 and 5339 incident cases, respectively). They found vitamin D deficiency was associated with an increased risk of dementia and stroke, with the strongest associations for those with 25(OH)D <25 nmol/L.
Health effects of meat consumption
Meat seems to be increasingly under attack, yet research does not support this negativity. The opposite is the case.
Frederic Leroy and colleagues conducted a systematic review. They implemented a meta-regression— relaxing conventional log-linearity assumptions and incorporating between-study heterogeneity—to evaluate the relationships between unprocessed red meat consumption and six potential health outcomes. They found weak evidence of the association between unprocessed red meat consumption and colorectal cancer, breast cancer, type 2 diabetes and ischemic heart disease. Moreover, they found no evidence of an association between unprocessed red meat and ischemic stroke or hemorrhagic stroke.
Meat intake and life expectancy
A study from Adelaide University looked at the association between meat intake and life expectancy at a population level based on ecological data published by the United Nations agencies. Population-specific data were obtained from 175 countries/territories. Worldwide, bivariate correlation analyses revealed that meat intake positively correlates with life expectancies. This relationship remained significant when influences of caloric intake, urbanization, obesity, education and carbohydrate crops were statistically controlled. Stepwise linear regression selected meat intake, not carbohydrate crops, as one of the significant predictors of life expectancy. In contrast, carbohydrate crops showed a weak and negative correlation with life expectancy.
Lisa Sanders and colleagues conducted a systematic review and meta-analysis were conducted on RCTs evaluating the effects of diets containing red meat (beef, pork, lamb, etc.), compared to diets with lower or no red meat, on markers of glucose homeostasis in adults. The results of this meta-analysis suggest red meat intake does not impact most glycemic and insulinemic risk factors for T2D.
Meat and mental health
Dobersek et al reviewed studies examining the relationship between meat intake and anxiety/depression. Twenty studies met the selection criteria representing 171,802 participants, with 157,778 meat consumers and 13,259 meat abstainers. Meat consumption was associated with lower depression and lower anxiety.
Debunking the vegan myth
An article from O’Keefe with Loren Cordain as senior author looked at the health effects of vegan and omnivore diets and concluded that strict adherence to a vegan diet causes predictable deficiencies in nutrients, including vitamins B12, B2, D, niacin, iron, iodine, zinc, high-quality proteins, omega-3, and calcium. Prolonged strict veganism increases risk of bone fractures, sarcopenia, anemia, and depression. A more logical diet is a plant-forward omnivorous eating pattern that emphasizes the generous consumption of natural, unprocessed foods predominantly from plants. To balance this diet, modest amounts of wholesome animal foods, such wild-caught fish/seafood, pasture-raised meat and eggs, and fermented unsweetened dairy, should be consumed regularly.
Saturated fatty acids
You would think by now there was enough evidence to conclude once and for all that saturated fat is not a cardiovascular risk factor, but it seems some people will never change their minds. 2022 brought more papers, including this editorial from Francesca Cortese.
Fats and cardio-metabolic outcomes
Another Italian group looked at various types of fats and their relationship to metabolic disease and found that consumption of SFA does not seem to be harmful to cardio-metabolic health; on the contrary, short-chain saturated fatty acids may be exert beneficial effects.
Saturated fats and type 2 diabetes
A systematic review and meta-analysis were conducted to pool findings of cohort studies that investigated hazards of type 2 diabetes mellitus (T2DM) in relation to intakes of SFAs. Thirteen cohort studies with 361,686 participants and 11,865 type 2 diabetes events were included. Dietary total SFA intake and dietary palmitic acid or stearic acid were not associated with the risk of T2DM when the highest was compared with the lowest intake. However, the risk of T2DM decreased by 11% in the highest compared with the lowest category of dietary lauric acid and by 17% in the highest compared with the lowest category of dietary myristic acid.
A short history of saturated fats
Nina Teicholz is always worth reading.
Sugar rush or sugar crash?
A group of psychologists conducted a systematic review and meta-analysis to evaluate the relationship between acute CHO ingestion and mood. They examined the time course of CHO–mood interactions and considered the role of moderator variables potentially affecting the CHO–mood relationship. Analysis of 176 effect sizes (31 studies, 1259 participants) revealed no positive effect of CHOs on mood following their consumption. However, CHO administration was associated with higher fatigue levels and less alertness than placebo within the first-hour post-ingestion.
Keto and mental illness
Shebani Sethi from Stanford describes evidence that the ketogenic diet’s metabolic, neuroprotective, and neurochemical benefits could provide symptomatic relief to people with schizophrenia while improving their cardiovascular or metabolic health. They reviewed the evidence for KD side effects and noted that although high in fat, it improves various cardiovascular and metabolic risk markers in overweight/obese individuals.
Ketogenic diets and disease
A systematic review and meta-analysis looked at the efficacy and safety of diet therapies in autism spectrum disorder. Of the 7 RCTs with 338 participants, two studies that followed the gluten-free diet reported significant reductions in social behaviours with no correlation with the length of the interventions (P < 0.05), and two studies performed using the ketogenic diet suggested a significant effect in core symptoms.
The role of stress in T2D is often discussed so it was good to see a review on this topic.
Keto and refractory mental illness
And finally, Frontiers in Psychiatry had several nutrition-related articles.
Firstly a paper with Eric Westman, Laura Saslow and Georgia Ede as co-authors reviewed a series of 31 adults with severe, persistent mental illness (major depressive disorder, bipolar disorder, and schizoaffective disorder) whose symptoms were poorly controlled despite intensive psychiatric management were admitted to a psychiatric hospital and placed on a ketogenic diet restricted to a maximum of 20 grams of carbohydrate per day as an adjunct to conventional inpatient care. There were significant improvements in depression and psychosis symptoms and multiple markers of metabolic health.
Low carb and psychoeducational programs
And Jen Unwin and colleagues focused on a whole food low-carbohydrate approach and delivering educational materials and psychosocial support relating to food addiction recovery. Food addiction symptoms were significantly reduced across settings, and body weight was reduced 2.34 kg. Mental well-being showed significant improvements across all settings.
Eric Kossoff begins this review of the use of ketogenic diet in epilepsy by noting it is now 100 years since the first report in the medical literature of its benefit. It remains a useful and effective therapy for epilepsy as well as being the treatment of choice for certain metabolic conditions, such as Glut1 deficiency and pyruvate dehydrogenase deficiency.
Keto and MS
Since Terry Wahls alerted us to the potential impact of diet on multiple sclerosis with her excellent book and TED Talk, several studies have been published.
Lin and colleagues from Taiwan reviewed the three trials published before 2022 and animal studies and looked at possible mechanisms of action.
Benefits of keto in treatment of Multiple Sclerosis
In this 2022 trial, sixty-five subjects with relapsing MS enrolled on a 6-month prospective, intention-to-treat KD intervention. The study demonstrated that KDs are safe and tolerable over a 6-month study period and yield improvements in body composition, fatigue, depression, QoL, neurological disability and adipose-related inflammation in persons living with relapsing MS.
New Zealand neurologist Matt Phillips who published excellent studies on the use of the ketogenic diet in Parkinsons disease in 2018 and Alzheimers in 2021, published a case report of a 45-year-old man with progressively worsening Huntingdon’s disease. The man pursued a time-restricted ketogenic diet for 12 months, after which his motor symptoms improved by 52% and behaviour problems by 50-100%.
Children and low carb
Dietitian Caryn Zinn and her colleagues in Auckland looked at the potential risks and benefits of low carb diets in children by designing theoretical meal plans and assessing micronutrient values. All meal plans exceeded the minimum nutrient reference values thresholds for all micronutrients; protein slightly exceeded the AMDR recommendations by up to three percentage points. They concluded that LCHF meal plans could be energy-, protein-, and micronutrient-replete for children and adolescents.
Malcolm Kendrick is always provocative and thought-provoking…
Low-density lipoprotein (LDL)-cholesterol is a weak predictor of cardiovascular risk. Factors that drive endothelial damage and thrombus formation greatly increase the risk of atherosclerotic cardiovascular disease (ASCVD). The thrombogenic hypothesis that endothelial damage and subsequent clot formation underlies the formation and growth of plaques can explain several causal risk factors that do not fit within the LDL-cholesterol hypothesis, including type II diabetes, smoking and systemic lupus erythematosus. They may represent a better model for ASCVD. There is a need to research the thrombogenic hypothesis in more depth.
Cardiometabolic health in the USA
A couple of years ago it was suggested that only 12% of Americans were “metabolically healthy”. Dariush Mozaffarian and his group gave us an update which looks ever worse – depressing!
They assessed proportions of adults with optimal cardiometabolic health, based on adiposity, blood glucose, blood lipids, blood pressure, and clinical CVD; and optimal, intermediate, and poor levels of each component among 55,081 U.S. adults in the National Health and Nutrition Examination Survey. In 2017-2018, only 6.8% of U.S. adults had optimal cardiometabolic health, declining from 1999-2000. Disparities by age, sex, education, and race/ethnicity were evident in all years, and generally worsened over time.
And finally an equally depressing article highlighting the degree of corporate influence on the nutrition profession in the USA.
My Book of the Year
Lots of good books as always, but the one I most enjoyed reading was Malcolm Kendrick’s “The Clot Thickens”. Great title, great book. If you haven’t already read it, do so now.
Honourable mentions to:
- Jayne Buxton The Great Plant-based Con
- Chris Palmer Brain Energy
My Podcast of the Year
The Low Carb MD somehow get all the big names of the low carb world, even some of us from the other side of the world!
Honourable mentions to:
- Diet Doctor Podcast with Dr Brett Scher
- The Drive with Peter Attia
- The Fabulously Keto Podcast with Jackie Fetcher and Louise Reynolds
My Blog of the Year
That’s an easy one. Every Monday, I know I will have a great read because that’s when Zoe Harcombe sends out her weekly blog critically examining a research or review paper on topics related to diet and health. I have learnt a lot from Zoe. No-one does it better. You should subscribe!
Honourable mentions to:
And that’s a wrap! Let me know of any important topics, studies, books or podcasts that I’ve missed.