Sixty per cent of people with depression still do not seek medical help because of the social stigma around its perceived hindrance to their career or personal life.[1]
Suppose you are one of those sixty per cent.
In that case, managing your blood sugar and exercise could be two lifestyle choices that can begin your journey towards feeling better, especially if you are not ready to see a medical practitioner and use anti-depressants.
Before we get into it, here is a personal responsibility disclaimer. If there comes a time when you feel like it is difficult for you to take action and the quality of your day is declining rapidly, then getting some help can be life-changing.
I have seen people’s lives change personally and in my clinical practice once they have felt brave enough to ask for help.
Depression and anxiety, which I’m going to try and address independently as best I can in this article, have many different causes. Causes often overlap for both conditions.
For example, just from a physiology standpoint, genetics, the brain, your hormones and your immune system could all interact at any one time in a challenging way to pin down.
Sometimes though, the causes that excite your depression and anxiety may not be what you expect at all.
If you have read the article on sleep and low blood sugar, you might have come across this already. I’ve lost count of how people I’ve helped to move off their sleep aids after treating their blood sugar.
Dysfunctional blood sugar and insulin levels have huge effects on your brain chemistry.
These changes may be enough to affect how your brain fuels itself with glucose. It could also cause immune changes in the brain that make it more inflamed and even affect the access amino acids that create neurotransmitters like serotonin and dopamine get when travelling to the brain from the stomach.
Let’s begin with how unstable blood sugar can affect your brain’s ability to fuel itself.
The brain is the highest glucose consumer of all the organs in the body, meaning it needs a constant and consistent supply of glucose at all times.[2]
Neurons have the highest energy demand in the brain.[3] The reason is that glucose is the building block of cellular energy, ATP.
Enter the mitochondria, “the powerhouse of the cells.”
You may have heard of mitochondria before in your reading. Their role is to provide energy for cells to function. An easy way to understand their role is via their increased or decreased concentration in different areas of the body.
For example, cells, like the ones in the brain, that are involved in intense functional activities need more energy. Therefore, they contain higher amounts of mitochondria than cells that require less energy to pay for their function.
Another way to think about it is that larger engines need bigger fuel tanks.
Consequently, when the primary fuel source runs low, the mitochondria cannot turn over the necessary energy to fuel the different functions in the brain. We begin to see cognitive changes first before depressive, or anxious states develop.
This trend lines up with how people feel mentally and cognitively when their blood glucose is too low.
One of the most common clinical signs that blood sugar affects the brain is memory and attention. One paper highlighted that low blood sugar, think low fuel for the brain, caused a significant deterioration in reading span and language processing. [4]
I see this commonly with fatigue patients in the clinic. The good news is I can help you differentiate it with the same questions I use in my consultations, as we often see fatigue, depression and anxiety overlap.
The first question concerns physical capacity and enquires about your capacity to run 400m.
The second question and most appropriate here is an enquiry around energy when it comes to reading a 2000-word article, kind of like this one!
More often than not, people feel relatively confident to run 400m but are not when it comes to maintaining their concentration and attention mentally.
How about you? Is your blood sugar affecting your mood and anxiety?
Whilst depression and anxiety might not be present; these signs indicate that the mitochondria in the brain may not be firing and fueling to their potential. If you get symptoms of low blood sugar at the same time, then it’s a good idea to look into some change.
Hypoglycemia has evidence around affecting other things aside from memory and attention. For example, there are studies around nonverbal intelligence, special awareness and executive function.[5]
Studies have shown significantly impaired mitochondrial function in major depressive disorder.[6]
And making sure your body can keep a consistent supply of glucose coming is of paramount importance.
There is a secret trick to helping to boost your mitochondria’s ability to keep that ATP coming.
And it’s the humble B-Complex vitamin. In other articles you might have come across on this site, I’ve explained that an easy way to think about how vitamins and minerals work is to think of them as denominations of currency that pay for different transactions in the body.
In the case of mitochondria creating energy from glucose, Vitamin B1, B2, B3 and B5 all play a critical role in turning glucose into ATP, your cell’s energy. A process called the Krebs’ or Citric Acid cycle.
Try picking up a methylated B-complex to cover for any genetic deficits in dealing with folic acid and vitamin B12. You might find that some of the attention and memory deficits that come with low blood sugar dissipate along with anxiety and even low mood.
A review in 2016 linked vitamin B1, B3, B6, B9 and B12 deficiencies to depression.[7]
Based on this, you won’t only be helping balance the balance between glucose and energy, but you may also be having a therapeutic effect on your mood.
Having the right building blocks to build neurotransmitters is vital for depression and anxiety.
And unstable blood sugar and insulin resistance have a critical influence. Disordered blood sugar affects another pathway for the brain to access vital resources, and that’s getting access to amino acids from protein that help to create necessary brain chemicals such as serotonin and dopamine.
Evidence suggests that insulin resistance plays a significant role in major depressive disorder. In fact, people with type-2 diabetes are twice as likely to suffer from depression. This higher risk is largely down to insulin’s influence on the serotonergic system in the brain, which controls emotional behaviour.[8]
It goes both ways, though. Studies going back almost twenty years have shown that people with depression develop insulin resistance, which corrects itself when the depression does.[9]
If you are new to insulin resistance, let’s define it. Insulin resistance occurs when an impaired response to glucose makes insulin less active and sensitive to glucose levels in the blood.[10]
This inadequate response to glucose means the body can have trouble depositing and transporting glucose correctly, leading to various cardiovascular and metabolic changes over time. For context, insulin resistance precedes type-2 diabetes by ten to fifteen years.[11]
But how does insulin affect brain chemicals such as serotonin or dopamine?
Let’s look at tryptophan, the amino acid that creates serotonin is called a large neutral amino acid. There are around four or five other LNAAs, such as Leucine, Histidine, which produce histamine and methionine.
You don’t really need to know too much about these other LNAAs.
But what you do need to know is that the particular types of amino acids compete when it comes to transport to the brain. Insulin helps to get more tryptophan across the blood-brain barrier as a priority for serotonin production.
Suppose, though, that in the case of insulin resistance, insulin isn’t effective enough at making things happen and tryptophan no longer has priority seating on the bus into the brain?
This lower level of tryptophan in the brain means lower amounts of the critical building blocks for serotonin are available and, in turn, presents insulin resistance’s contribution to poor mood.
Insulin’s influence not only causes lower levels of serotonin that we see in depression, but we also see the tryptophan get shunted over to another pathway that can lead to neuroinflammation leading to more depression and anxiety.[12]
Animal studies have shown that insulin resistance, localised explicitly in the brain, can affect dopamine turnover, making depression and anxiety symptoms worse.[13]
Unfortunately, in the case of anxiety, it seems, as we saw in depression a little earlier, that it could be a two-way street.
It seems that not only do insulin resistance and impaired glucose balance cause changes in brain chemistry, but the associated stress associated with this change can rebound back and make the insulin resistance worse.[14]
This two-way effect between stress, depression and anxiety and insulin resistance is one of the critical reasons blood sugar issues seem to be a rate-limiting factor in helping mental health situations such as depression and anxiety.
Interestingly, recent, more cutting-edge studies suggest that balancing the bacterial environment in the gut, commonly known as the microbiota, may be the avenue to help with insulin resistance.[15]
What are the signs and symptoms of insulin resistance and hypoglycemia?
So you’ve read the article and are wondering whether or not blood sugar issues are appropriate in your own case. Here are the signs and symptoms of both hypoglycemia and insulin resistance.
Hypoglycemic symptoms in the brain directly related to low glucose in the central nervous system are behavioural changes, fatigue and confusion. Physical symptoms can be tremors, heart palpitations, hunger and sweating.[16]
Some more subjective symptoms can be no appetite in the morning, energy after meals, the 3 pm crash and difficulty staying asleep during the night.
Typical characteristics of Insulin resistance are weight gain and sugar cravings. More subjective symptoms can be waking up feeling unrefreshed, difficulty falling asleep, crashing after lunch and needing stimulants after lunch.
A critical difference between those with hypoglycemia and insulin resistance is how people respond to eating. People with hypoglycemia will have better energy after meals, and those with insulin resistance will have fatigue after meals.
In the clinic, I often see these experiences occurring with the same person but interchangeably. You will find that there’ll be a more prominent theme if you look at either’s frequency over time.
So what do you think?
There are many different origin stories of depression and anxiety. Each of these overlaps, and often you might need some help to deconstruct what’s what. Still, in the case of unbalanced blood sugar and your brain, precisely the quality of your daily mood and stress symptoms, it can be often overlooked and may hold the key you’ve been looking for to get things on track.
Hope this helps xx
References
[1] Chand SP, Arif H. Depression. [Updated 2022 Jul 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430847/
[2] Mergenthaler P, Lindauer U, Dienel GA, Meisel A. Sugar for the brain: the role of glucose in physiological and pathological brain function. Trends Neurosci. 2013;36(10):587-597. doi:10.1016/j.tins.2013.07.001
[3] Howarth C, Gleeson P, Attwell D. Updated energy budgets for neural computation in the neocortex and cerebellum. J Cereb Blood Flow Metab. 2012;32(7):1222-1232. doi:10.1038/jcbfm.2012.35
[4] Allen KV, Pickering MJ, Zammitt NN, et al. Effects of acute hypoglycemia on working memory and language processing in adults with and without type 1 diabetes. Diabetes Care. 2015;38(6):1108-1115. doi:10.2337/dc14-1657
[5] Allen KV, Pickering MJ, Zammitt NN, et al. Effects of acute hypoglycemia on working memory and language processing in adults with and without type 1 diabetes. Diabetes Care. 2015;38(6):1108-1115. doi:10.2337/dc14-1657
[6] Kuffner K, Triebelhorn J, Meindl K, et al. Major Depressive Disorder is Associated with Impaired Mitochondrial Function in Skin Fibroblasts. Cells. 2020;9(4):884. Published 2020 Apr 4. doi:10.3390/cells9040884
[7] Mikkelsen K, Stojanovska L, Apostolopoulos V. The Effects of Vitamin B in Depression. Curr Med Chem. 2016;23(38):4317-4337. doi:10.2174/0929867323666160920110810
[8] Martin H, Bullich S, Martinat M, et al. Insulin modulates emotional behavior through a serotonin-dependent mechanism [published online ahead of print, 2022 Oct 7]. Mol Psychiatry. 2022;10.1038/s41380-022-01812-3. doi:10.1038/s41380-022-01812-3
More references!
[9] Okamura F, Tashiro A, Utumi A, et al. Insulin resistance in patients with depression and its changes during the clinical course of depression: minimal model analysis. Metabolism. 2000;49(10):1255-1260. doi:10.1053/meta.2000.9515
[10] Freeman AM, Pennings N. Insulin Resistance. In: StatPearls. Treasure Island (FL): StatPearls Publishing; July 4, 2022.
[11] Freeman AM, Pennings N. Insulin Resistance. In: StatPearls. Treasure Island (FL): StatPearls Publishing; July 4, 2022.
[12] Oxenkrug G. Insulin resistance and dysregulation of tryptophan-kynurenine and kynurenine-nicotinamide adenine dinucleotide metabolic pathways. Mol Neurobiol. 2013;48(2):294-301. doi:10.1007/s12035-013-8497-4
[13] Kleinridders A, Cai W, Cappellucci L, et al. Insulin resistance in brain alters dopamine turnover and causes behavioral disorders. Proc Natl Acad Sci U S A. 2015;112(11):3463-3468. doi:10.1073/pnas.1500877112
[14] Yaribeygi H, Maleki M, Butler AE, Jamialahmadi T, Sahebkar A. Molecular mechanisms linking stress and insulin resistance. EXCLI J. 2022;21:317-334. Published 2022 Jan 24. doi:10.17179/excli2021-4382
[15] Sarwar H, Rafiqi SI, Ahmad S, et al. Hyperinsulinemia Associated Depression. Clin Med Insights Endocrinol Diabetes. 2022;15:11795514221090244. Published 2022 Apr 21. doi:10.1177/11795514221090244
[16] Mathew P, Thoppil D. Hypoglycemia. [Updated 2022 Jul 23]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK534841/
