By Robert H. Lustig, MD, MSL
Robert Lustig is Professor Emeritus of Pediatrics in the Division of Endocrinology, and Member of the Institute for Health Policy Studies at the University of California, San Francisco. He is a pediatric neuroendocrinologist,and an international authority on obesity, diabetes,nutrition,and neuroscience. He is the author of three books that have changed our understanding of the danger of sugar on our metabolism – Fat Chance, The Hacking of the American Mind, and Metabolical.
Most people know that refined sugar is not good for you, but what is it about sugar that’s particularly bad for your brain? Why is it essential, not only for brain health and dementia prevention, to reduce your intake of not only sugar but refined carbohydrates in general? (By refined, I mean those whose fiber has been processed away – not ‘whole’ as in vegetables, whole fruit (not juice), beans, and whole grains.
Let’s start at the extreme. What happens if you lived at the North Pole, and ate virtually no carbohydrates, or at least so little as to force your body and brain to switch to a kind of fuel, ketones, produced from fat? This is often called a “very low carb high fat” (LCHF) or “ketogenic” diet. Would you get sick? This is what Vilhjamur Steffanson did, when his Arctic exploration shipwrecked in 1913, and he was forced to live amongst the Inuit for two years. He noted that there was no diabetes, no cancer — and no Alzheimer’s. In 1928, he and his colleague checked themselves into Bellvue hospital, and ate only meat for one year.They were healthier than the researchers who studied them!
Your brain likes ketones
Ketones are made in the liver from fat – either breaking down your own fat (for example, if you were fasting, eating very little or exercising a lot), or from ingestion of a type of fat containing ‘medium chain triglycerides’ (MCTs). Coconut oil is approximately 54% MCTs and contains all 4 MCTs (C6, C8, C10, C12), but it turns out that one particular kind of MCT, called C8 because it is 8 carbons long, is the best fat for the liver to convert into ketones.
You may be surprised to know that your brain can run well on glucose (the kind of sugar that is fuel for our cells), but even better on ketones. The reason is that ketones cross into the brain easily, rapidly, and without a biochemical transporter. This is why children with severe epilepsy improve on a ketogenic diet. Watch this short film ‘Fuel your Brain’.
Brain benefits of a low-carb ketogenic diet
In fact, brain cells prefer ketones. In two studies, one on people with Alzheimer’s and the other on those with pre-dementia or mild cognitive impairment, giving 2 tablespoons of C8 oil (called capricin or caprylic acid triglyceride), brain energy derived from ketones went up by 230% and memory and mental acuity improved in those with Minimal Cognitive Impairment (MCI).[2,3]
A ketogenic diet has been shown to reduce schizophrenia symptoms, help reduce shaking in Parkinson’s, and slow down cognitive decline in those with dementia or pre-dementia. In fact, the ketogenic diet has been used to effectively treat childhood epilepsy for over 100 years! There’s a good review on the current status of the ketogenic diet in psychiatry here.
Ketogenic diets may help in many ways. Firstly, when a person eats too much carbohydrate, sugar, but especially fructose, damages the energy burning factories in cells, called mitochondria, so their ability to produce chemical energy for the neuron is greatly reduced. Switching to burning ketones instead can increase mitochondria number and function. A recent study also shows that a ketogenic diet has a positive effect on the gut microbiome, and this might be one way the diet helps reduce fits in people with epilepsy. Fructose, on the other hand, disrupts the gut microbiome in a negative way.
How sugar damages your brain
But what is it about a ketogenic diet that is good for your brain? Is it the ketones, the lowering of insulin, the type of fat, the elimination of carbohydrate, or specifically the elimination of sugar? We don’t yet know – I ask this question of every Alzheimer’s and metabolic researcher I know, and no one can tell me – just that it works.
There are a few possible mechanisms. First, the more carbs and sugar you eat, the more resistant you become to the hormone insulin. Insulin not only drives glucose into cells (including brain cells), but also sends excess sugar to the liver to turn into fat. When a person becomes insulin resistant, ironically, glucose transport is negatively impacted, reducing brain energy availability. Insulin resistance is a major driver of depression. A ketogenic diet can reverse that.
Fructose, which comprises half of sucrose (‘white’ or ‘table’ sugar), and half of ‘high-fructose corn syrup’ (added to numerous processed foods), damages our mitochondria, which leads to less brain energy availability. One study showed that fructose reduces liver mitochondrial function, while glucose stimulates it. “The most important takeaway of this study is that high fructose in the diet is bad,” said Dr. C. Ronald Kahn from the Joslin Diabetes Center. “It’s not bad because it’s more calories, but because it has effects on liver metabolism to make it worse at burning fat. As a result, adding fructose to the diet makes the liver store more fat, and this is bad for the liver and bad for whole body metabolism.”
Fructose is the main sugar in most fruits. People then extrapolate, “oh fruit must be bad for you.” Not true. Whole fruit has fibre (both soluble and insoluble); together they slow down glucose and fructose absorption in the GI tract limiting both liver and brain exposure, and they also help feed the gut bacteria (microbiome), so actually you get less fructose entering the bloodstream. Juicing the fruit removes the protective fiber, and juice has been shown to be just as dangerous to metabolism as is soda. So, eat your fruit — don’t drink it!
Carbohydrates and fructose age your brain
There’s another reason why sugar, and especially fructose, is bad for your brain and body. They produce Advanced Glycation Endpoints or AGEs, which damage the brain. These ‘oxidise’ proteins (so does cigarette smoke), rendering them useless , allowing them to aggregate into clumps, and use up valuable antioxidants in your diet such as vitamin C and E.
Fructose acts on your liver to switch your metabolism away from fat burning to fat making and storing, and inhibits an anti-ageing process called ‘autophagy’ which helps clean up and remove damaged mitochondria in order to regenerate new, healthier cells.
Why sweet foods are so addictive
So far we’ve only explored why sugar is bad for your “physical” brain. Knowing this is a good start. But why does your “emotional” brain keep telling you that you want it? Why do people find it so hard to resist, and so many become sugar addicts? The answer is that fructose activates the “reward system” in the brain. It causes dopamine release, the motivational neurotransmitter associated with ‘reward’. Any chemical that does so can be addictive – cocaine, heroin, alcohol, nicotine, or example. The trouble is the more you have, the more your brain ‘down-regulates’, i.e. becomes less responsive to your own natural feel-good dopamine, so you end up needing more sugar to get the hit and, in the end, you get no hit at all but feel thoroughly awful without it. That’s the Law of Diminishing Returns. That’s addiction.
Blood sugar control reduces dementia risk
Keeping blood glucose levels in the low-normal range is reflected by a low blood glycosylated haemoglobin (HbA1C) level, which means ‘sugar-coated red blood cells’. A low HbA1c is good and is a proxy for improved insulin sensitivity, associated with reduced risk for dementia in several studies.[9,10,11,12,13,14]
A new study also shows that, in 40 year old adults with so-called normal glucose levels but at the higher end of the normal range, have increased their risk of Alzheimer’s by 15% 
Type 2 diabetes, the net result of losing blood sugar control, almost doubles the risk for dementia.[15,16] Diabetes is also associated with more rapid brain shrinkage.[17,18] Even people in the upper normal range of blood glucose have increased brain atrophy, impaired cognition, and increased risk of dementia.[19,20]
For instance, one trial measured HbA1c and glucose levels in several thousand elderly people over the course of almost seven years. In that time, slightly more than a quarter of the participants developed dementia, and the bottom line was that rising glucose levels were associated with increased risk of developing the condition, irrespective of whether the participants also had diabetes. Non-diabetics who experienced a modest increase in blood sugar levels had an 18% increased risk of dementia, as compared to those who already had diabetes at the start of the study or developed it within the trial period, who had a 40% increased risk.
Insulin resistance is strongly related to cognitive decline
But even more important than loss of glucose control is the loss of insulin control. Back in 2004, researchers at Columbia University showed that people with high insulin levels – the principal hallmark of metabolic dysfunction – were twice as likely to develop dementia as those with healthy levels. Moreover, those with the highest insulin levels had the worst memory retrieval. The same year, an Italian study established a link between heightened insulin levels and declining mental function. Similarly, a Puerto Rican study found that people who consumed the large amounts of sugar doubled their risk of suffering poor cognitive function, while another US study discovered a strong correlation between blood sugar level and memory loss.
Two studies – one in Ireland, and the other in the United States, – established a link between high dietary glycemic load (GL; how high does your blood glucose rise when you eat carbohydrate) and cognitive decline. Indeed, both of these reports suggested that high GL is even more predictive of the pathological changes associated with Alzheimer’s than either high carb or high sugar intake. A high GL diet is also associated with more amyloid plaque and more cognitive decline, especially in those who carry the ApoE4 gene, a regulator of fat metabolism.
A long-term study found evidence that this sort of shrinkage is more common among people with high blood glucose levels, even when those levels are still within what are considered ‘normal’ (i.e. non-diabetic) limits. This cognitive decline starts young. Cognitive decline in overweight children is associated with a high GL diet, and adolescents with metabolic dysfunction driven by a high GL diet have been shown to have shrinkage of the hippocampal area of the brain, as well as other structural changes and cognitive deficits. [32,33]
Prevention action – how to cut down your sugar load
In practical terms, preventing dementia today means avoiding sugar as much as possible. If you’re going to eat carbohydrate, eat ‘whole’ carbohydrate foods such as whole vegetables, fruits (not juice), beans, only wholegrain bread (labelled as ‘100% wholegrain’, or pasta in small quantities.
Starchy carbohydrates such as pasta, rice and potatoes benefit from being cooked and cooled, then eaten cold or re-heated, as some of the carbohydrate is converted into resistant starch – a type of fibre we can’t digest but which has the added benefit of fermenting and feeding our gut bacteria.
Make sure the carbohydrate comes with its inherent fibre. Oat cakes would be better than bread since the fibre in these foods helps ‘slow release’ the sugars. Eating white bread is associated with a poorer cognitive test performance, whereas high fibre bread is associated with better performance. Eating carbohydrate foods with protein, for example brown rice with fish, or porridge oats with seeds, or fruit with nuts, further reduces the glycemic load (GL) of a meal. The best fruits in this respect are low-sugar high-fiber fruits like berries, cherries, and plums.
These kinds of foods are consistent with a Mediterranean diet which has also been shown to reduce risk. Conversely, grapes, raisins, and bananas are high GL. A study in Finland and Sweden compared those with a healthy versus unhealthy diet, including the above criteria, in mid-life for future risk of developing Alzheimer’s disease and dementia 14 years later. Those who ate the healthiest diet had an 88% decreased risk of developing dementia and a 92% decreased risk of developing Alzheimer’s disease.
The take-home message is, if you are going to eat complex carbohydrates, eat them with fibre, fat and protein.
However, if you want to go one step further, you can switch to eating a ketogenic low-carb, high fat diet. The problem with the ketogenic diet is staying on it – there’s so much carbohydrate out there it’s hard to avoid it. But there are now breath monitors (e.g. Ketoscan, BioSense from ReadOut Health) that can help you stay in ketosis. A good book to help you explore and put into practice either a low carb ketogenic diet or a low GL diet is ‘The Hybrid Diet’ by Patrick Holford & Jerome Burne. And to understand how processed food is your enemy, take a look at my book ‘Metabolical’.
And if you want to know how sugar is impacting your body and brain then upi can take one of our at-home, pin-prick, HbA1c (sugar) blood test so you can know exactly how sugar is impacting your body and also become apart of our vital research into this area.
1. Heinbecker P. STUDIES ON THE METABOLISM OF ESKIMOS. Journal of Biological Chemistry. 1928 Dec;80(2):461–75.
2. Fortier M, Castellano C-A, St-Pierre V, Myette-Côté É, Langlois F, Roy M, et al. A ketogenic drink improves cognition in mild cognitive impairment: Results of a 6-month RCT. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association [Internet]. 2020 Oct 26; Available from: https://pubmed.ncbi.nlm.nih.gov/33103819/
3. Croteau E, Castellano C-A, Richard MA, Fortier M, Nugent S, Lepage M, et al. Ketogenic Medium Chain Triglycerides Increase Brain Energy Metabolism in Alzheimer’s Disease. Journal of Alzheimer’s disease: JAD [Internet]. 2018;64(2):551–61. Available from: https://pubmed.ncbi.nlm.nih.gov/29914035/
4. Bostock ECS, Kirkby KC, Taylor BVM. The Current Status of the Ketogenic Diet in Psychiatry. Frontiers in psychiatry [Internet]. 2017;8:43. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28373848
5. Paoli A, Mancin L, Bianco A, Thomas E, Mota JF, Piccini F. Ketogenic Diet and Microbiota: Friends or Enemies? Genes. 2019 Jul 15;10(7):534
6. Olson CA, Vuong HE, Yano JM, Liang QY, Nusbaum DJ, Hsiao EY. The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet. Cell [Internet]. 2018 Jun [cited 2019 Apr 17];173(7):1728-1741.e13. Available from: https://www.cell.com/cell/pdf/S0092-8674(18)30520-8.pdf
7. Watson K, Nasca C, Aasly L, McEwen B, Rasgon N. Insulin resistance, an unmasked culprit in depressive disorders: Promises for interventions. Neuropharmacology [Internet]. 2018 Jul 1 [cited 2022 Aug 5];136(Pt B):327–34. Available from: https://pubmed.ncbi.nlm.nih.gov/29180223/
8. Softic S, Meyer JG, Wang G-X, Gupta MK, Batista TM, Lauritzen HPMM, et al. Dietary Sugars Alter Hepatic Fatty Acid Oxidation via Transcriptional and Post-translational Modifications of Mitochondrial Proteins. Cell Metabolism [Internet]. 2019 Oct;30(4):735-753.e4. Available from: https://www.cell.com/cell-metabolism/pdfExtended/S1550-4131(19)30504-2
9. Luchsinger JA, Tang M-X ., Shea S, Mayeux R. Hyperinsulinemia and risk of Alzheimer disease. Neurology. 2004 Oct 11;63(7):1187–92.
10. Abbatecola AM, Paolisso G, Lamponi M, Bandinelli S, Lauretani F, Launer L, et al. Insulin Resistance and Executive Dysfunction in Older Persons. Journal of the American Geriatrics Society. 2004 Oct;52(10):1713–8.
11. Xu WL, von Strauss E, Qiu CX, Winblad B, Fratiglioni L. Uncontrolled diabetes increases the risk of Alzheimer’s disease: a population-based cohort study. Diabetologia. 2009 Mar 12;52(6):1031–9.
12. Hassing Lb, Grant Md, Hofer Sm, Pedersen Nl, Nilsson Se, Berg S, et al. Type 2 diabetes mellitus contributes to cognitive decline in old age: A longitudinal population-based study. Journal of the International Neuropsychological Society. 2004 Jul;10(4):599–607.
13. Yaffe K, Blackwell T, Whitmer RA, Krueger K, Barrett Connor E. Glycosylated hemoglobin level and development of mild cognitive impairment or dementia in older women. The Journal of Nutrition, Health & Aging [Internet]. 2006 Jul 1 [cited 2022 Aug 5];10(4):293–5. Available from: https://pubmed.ncbi.nlm.nih.gov/16886099/
14. Roberts RO, Knopman DS, Cha RH, Mielke MM, Pankratz VS, Boeve BF, et al. Diabetes and Elevated Hemoglobin A1c Levels Are Associated with Brain Hypometabolism but Not Amyloid Accumulation. Journal of Nuclear Medicine. 2014 Mar 20;55(5):759–64.
15. Arvanitakis Z, Wilson RS, Bienias JL, Evans DA, Bennett DA. Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. Arch Neurol. 2004 May;61(5):661-6. doi: 10.1001/archneur.61.5.661. PMID: 15148141.
16. Yaffe K, Blackwell T, Kanaya AM, Davidowitz N, Barrett-Connor E, Krueger K. Diabetes, impaired fasting glucose, and development of cognitive impairment in older women. Neurology [Internet]. 2004 Aug 24 [cited 2022 Mar 16];63(4):658–63. Available from: https://n.neurology.org/content/63/4/658
17. Tiehuis AM, van der Graaf Y, Visseren FL, Vincken KL, Biessels GJ, Appelman APA, et al. Diabetes Increases Atrophy and Vascular Lesions on Brain MRI in Patients With Symptomatic Arterial Disease. Stroke. 2008 May;39(5):1600–3.
18. Samaras K, Lutgers HL, Kochan NA, Crawford JD, Campbell LV, Wen W, et al. The impact of glucose disorders on cognition and brain volumes in the elderly: the Sydney Memory and Ageing Study. AGE [Internet]. 2014 Jan 9 [cited 2022 Aug 5];36(2):977–93. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039246/
19. Mortby ME, Janke AL, Anstey KJ, Sachdev PS, Cherbuin N. High “normal” blood glucose is associated with decreased brain volume and cognitive performance in the 60s: the PATH through life study. PLoS One. 2013 Sep 4;8(9):e73697. doi: 10.1371/journal.pone.0073697. PMID: 24023897; PMCID: PMC3762736.
20. Crane PK, Walker R, Hubbard RA, Li G, Nathan DM, Zheng H, Haneuse S, Craft S, Montine TJ, Kahn SE, McCormick W, McCurry SM, Bowen JD, Larson EB. Glucose levels and risk of dementia. N Engl J Med. 2013 Aug 8;369(6):540-8. doi: 10.1056/NEJMoa1215740. Erratum in: N Engl J Med. 2013 Oct 10;369(15):1476. PMID: 23924004; PMCID: PMC3955123.
21. Crane PK, Walker R, Hubbard RA, Li G, Nathan DM, Zheng H, Haneuse S, Craft S, Montine TJ, Kahn SE, McCormick W, McCurry SM, Bowen JD, Larson EB. Glucose levels and risk of dementia. N Engl J Med. 2013 Aug 8;369(6):540-8. doi: 10.1056/NEJMoa1215740. Erratum in: N Engl J Med. 2013 Oct 10;369(15):1476. PMID: 23924004; PMCID: PMC3955123.
22. Luchsinger JA, Tang MX, Shea S, Mayeux R. Hyperinsulinemia and risk of Alzheimer disease. Neurology. 2004 Oct 12;63(7):1187-92. doi: 10.1212/01.wnl.0000140292.04932.87. PMID: 15477536.
23. Abbatecola AM, Paolisso G, Lamponi M, Bandinelli S, Lauretani F, Launer L, Ferrucci L. Insulin resistance and executive dysfunction in older persons. J Am Geriatr Soc. 2004 Oct;52(10):1713-8. doi: 10.1111/j.1532-5415.2004.52466.x. PMID: 15450050.
24. Ye X, Gao X, Scott T, Tucker KL. Habitual sugar intake and cognitive function among middle-aged and older Puerto Ricans without diabetes. Br J Nutr. 2011 Nov;106(9):1423-32. doi: 10.1017/S0007114511001760. Epub 2011 Jun 1. PMID: 21736803; PMCID: PMC4876724.
25. Seetharaman S, Andel R, McEvoy C, Dahl Aslan AK, Finkel D, Pedersen NL. Blood glucose, diet-based glycemic load and cognitive aging among dementia-free older adults. J Gerontol A Biol Sci Med Sci. 2015 Apr;70(4):471-9. doi: 10.1093/gerona/glu135. Epub 2014 Aug 22. PMID: 25149688; PMCID: PMC4447796.
26. Power SE, O’Connor EM, Ross RP, Stanton C, O’Toole PW, Fitzgerald GF, Jeffery IB. Dietary glycaemic load associated with cognitive performance in elderly subjects. Eur J Nutr. 2015 Jun;54(4):557-68. doi: 10.1007/s00394-014-0737-5. Epub 2014 Jul 18. PMID: 25034880.
27. Taylor MK, Sullivan DK, Swerdlow RH, Vidoni ED, Morris JK, Mahnken JD, Burns JM. A high-glycemic diet is associated with cerebral amyloid burden in cognitively normal older adults. Am J Clin Nutr. 2017 Dec;106(6):1463-1470. doi: 10.3945/ajcn.117.162263. Epub 2017 Oct 25. PMID: 29070566; PMCID: PMC5698843.
28. Taylor MK, Sullivan DK, Swerdlow RH, Vidoni ED, Morris JK, Mahnken JD, Burns JM. A high-glycemic diet is associated with cerebral amyloid burden in cognitively normal older adults. Am J Clin Nutr. 2017 Dec;106(6):1463-1470. doi: 10.3945/ajcn.117.162263. Epub 2017 Oct 25. PMID: 29070566; PMCID: PMC5698843.
29. Gentreau M, Raymond M, Chuy V, Samieri C, Féart C, Berticat C, Artero S. High Glycemic Load Is Associated with Cognitive Decline in Apolipoprotein E ε4 Allele Carriers. Nutrients. 2020 Nov 25;12(12):3619. doi: 10.3390/nu12123619. PMID: 33255701; PMCID: PMC7761247.
30. M.E. Mortby et al., ‘High “normal” blood glucose is associated with decreased brain volume and cognitive performance in the 60s: the PATH through Life Study’, PLoS One (2013), vol 8:e73697.
31. Lakhan, S.E., Kirchgessner, A. The emerging role of dietary fructose in obesity and cognitive decline. Nutr J 12, 114 (2013). https://doi.org/10.1186/1475-2891-12-114
32. Yau PL, Castro MG, Tagani A, Tsui WH, Convit A. Obesity and metabolic syndrome and functional and structural brain impairments in adolescence. Pediatrics. 2012 Oct;130(4):e856-64. doi: 10.1542/peds.2012-0324. Epub 2012 Sep 3. PMID: 22945407; PMCID: PMC3457620.
33. Mangone A, Yates KF, Sweat V, Joseph A, Convit A. Cognitive functions among predominantly minority urban adolescents with metabolic syndrome. Appl Neuropsychol Child. 2018 Apr-Jun;7(2):157-163. doi: 10.1080/21622965.2017.1284662. Epub 2017 Feb 22. PMID: 28631969.
34. Loef M, Walach H. Fruit, vegetables and prevention of cognitive decline or dementia: a systematic review of cohort studies. J Nutr Health Aging. 2012 Jul;16(7):626-30. doi: 10.1007/s12603-012-0097-x. PMID: 22836704.
35. Martínez-Lapiscina EH, Clavero P, Toledo E, Estruch R, Salas-Salvadó J, San Julián B, Sanchez-Tainta A, Ros E, Valls-Pedret C, Martinez-Gonzalez MÁ. Mediterranean diet improves cognition: the PREDIMED-NAVARRA randomised trial. J Neurol Neurosurg Psychiatry. 2013 Dec;84(12):1318-25. doi: 10.1136/jnnp-2012-304792. Epub 2013 May 13. PMID: 23670794.
36. Eskelinen MH, Ngandu T, Tuomilehto J, Soininen H, Kivipelto M. Midlife healthy-diet index and late-life dementia and Alzheimer’s disease. Dement Geriatr Cogn Dis Extra. 2011 Jan;1(1):103-12. doi: 10.1159/000327518. Epub 2011 Apr 27. PMID: 22163237; PMCID: PMC3199886.
37. Zhang X, Tong T, Chang A, Ang TFA, Tao Q, Auerbach S, Devine S, Qiu WQ, Mez J, Massaro J, Lunetta KL, Au R, Farrer LA. Midlife lipid and glucose levels are associated with Alzheimer’s disease. Alzheimers Dement. 2023 Jan;19(1):181-193. doi: 10.1002/alz.12641. Epub 2022 Mar 23. PMID: 35319157; PMCID: PMC10078665.