Depression and Diabetes - it's not all in your head
Diabetes is a complex, long-term disease that affects your day-to-day life, and can add a burden to an already complicated life. Yet, the relationship between depression and diabetes isn’t clearly known; it is very much a chicken vs. egg question: does depression predispose to diabetes? Or vice versa?
Depression is important to detect and treat in diabetes because diabetes requires special attention to self-care, and making good choices that lead to improved health and physical fitness anytime you can; depression can be a huge barrier to making healthful choices, including dietary choices and seeing your doctor on schedule.
Depression is important to detect and treat in diabetes because diabetes requires special attention to self-care...
In this article I will review what we know about the relationship between depression and diabetes, and review some conventional and natural treatment options. Be warned, some interactions between natural depression treatments and medications for diabetes may be significant - so speak with a trained professional!
So, how do you know if you are depressed and, more importantly, what can you do about it? Read on. Most importantly, if you believe you may have depression- talk to your doctor and/or complementary health care provider about your treatment options.
Thanks to the effective marketing of the drug Prozac, the average adult has heard of “serotonin” and has a general idea that having more of it around in the brain appears to be a good thing. Serotonin is only one neurotransmitter that impacts mood, but it appears to be a rather important one. Other important neurotransmitters that regulate mood include epinephrine, norepinephrine, and dopamine.
The conversion of tryptophan into serotonin or melatonin appears to be controlled by - guess what? - vitamin D!
Serotonin is made by the body in the brain from an amino acid named tryptophan; amino acids are the smaller building blocks of proteins in the body and come from dietary protein like meat, fish, dairy and grains. Serotonin performs many bodily functions, including mood, but also regulates blood flow to the brain and the stomach.
Interestingly tryptophan is also a precursor to the neurotransmitter melatonin. Perhaps you may have heard about melatonin as a natural sleep aid? Melatonin is also the “hibernation” hormone, because it is in higher concentrations in the winter. The conversion of tryptophan into serotonin or melatonin appears to be controlled by - guess what? - vitamin D! As you may recall, vitamin D is made in our skin in response to sunlight which is why some degree of seasonal depression - or really mild hibernation - is normal! (See Complementary Corner, March 2007 for more information about vitamin D)
Let me explain. During the winter months the intensity of sunlight is lower, and we are outdoors less. Our vitamin D levels tend to be lower, and thus so is our serotonin (our melatonin tends to be higher). This is why, during the winter season, most people have lower physical energy, lower libido, and a reduced mood - all of these symptoms tend to last until spring.
...when the carbohydrate cravings strike... your body is really asking you for more protein and vitamin D.
The other fascinating connection relates to carbohydrate cravings, and how they impact serotonin production. It turns out that when you eat and your body releases insulin, the insulin helps selectively remove amino acids from the blood into the liver and the muscles, however tryptophan is left in the blood for the brain to absorb . Thus carbohydrate cravings may actually be tryptophan cravings! So during the winter months, when the carbohydrate cravings strike, seek the sunlight or eat a higher protein meal instead. Your body is really asking you for more protein and vitamin D!
What is “depression” and how do I know if I have it?
We all have good days and bad days, our mood ebbs and flows depending on feedback we got at work, how things are going in our family, whether or not we made the bus on time that day, etc. These swings are normal, and not likely to be considered depression. However, if you always feel blue, have difficulty sleeping or sleep too much, have had a change in body weight (either weight loss or gain), or just can’t concentrate, you may have depression.
According to the National Institute of Mental Health , the symptoms of depression include:
- Persistent sad, anxious or "empty" feelings
- Feelings of hopelessness and/or pessimism
- Feelings of guilt, worthlessness and/or helplessness
- Irritability, restlessness
- Loss of interest in activities or hobbies once pleasurable, including sex
- Fatigue and decreased energy
- Difficulty concentrating, remembering details and making decisions
- Insomnia, early morning wakefulness, or excessive sleeping
- Overeating, or appetite loss
- Thoughts of suicide, suicide attempts
- Persistent aches or pains, headaches, cramps or digestive problems that do not ease even with treatment
Reputable online medical resources offer depression screening questionnaires; one example is WebMD. There depression questionnaire can be completed here.
If you score high, and suspect depression, talk to your doctor or complementary health care provider about your treatment options.
Depression - the chicken or the egg?
Depression appears to be more common in people who have diabetes than in similar adults without diabetes. Estimates from the United States show nearly double the rate of depression in adults with diabetes . Given the discussion above regarding carbohydrate cravings and their affect on serotonin production, it is reasonable to ask, which comes first, the depression or the diabetes? Does a depressed mood and increased stress lead to more carbohydrate cravings and thus diabetes? Or does the burden of diabetes lead to more depression because it is such a difficult disease?
The question has been asked in several large studies, following very large numbers of people for quite a while and it turns out there is evidence for both scenarios, so we don’t know for sure.
Depression appears to be more common in people who have diabetes than in similar adults without diabetes.
For example, in a large study of approximately 6,500 people, called the Multi-ethnic Study of Atherosclerosis (MESA), depression was associated with having treated diabetes, but not with pre-diabetes or un-treated diabetes, suggesting diabetes may come first. However, this study could not determine a temporal relationship between diabetes and depression [4.]
In the National Health and Nutrition Examination Survey (NHANES), a very large survey in the United States, symptoms of depression did not increase the risk of developing diabetes during the nine-year follow-up study . However, the Atherosclerosis Risk in Communities study of over 11,000 people in the United States, demonstrated a 63% increased risk of developing diabetes in the participants with the most symptoms of depression, compared to those with the least symptoms .
So, the mystery persists. I suspect both scenarios are true: those people with the greatest symptoms of depression are more likely to make poor diet choices and probably be less active. And, once some people develop diabetes, the extra attention required to health and the medical burden of the disease likely leads to feelings of depression.
So why should I care about depression in diabetes?
...depression appears to increase mortality, i.e. the risk of death in older adults.
The obvious answer is that you should care because effective natural and pharmaceutical treatments exist. Isn’t life too short to walk around sad?
The more medical answer is that depression appears to increase mortality, i.e. the risk of death in older adults. In fact, the risk of death related to depression was nearly equivalent to the risk of death following a heart attack, or from diabetes alone!  Imagine the risk from the combination of diabetes and depression! In the short term, people with diabetes and depression appear to be more likely to smoke, less likely to take their prescribed medications for diabetes, and less likely to follow dietary advice and get more exercise [8,9,10].
What treatments have been studied? Do they work?
The results have been mixed on the treatment of depression in diabetes, depending on the exact question asked. Improving the detection and treatment of depression in medical clinics appears to “work” in identifying and treating those people with depression, and in most cases, depression symptoms appear to improve . The more difficult issue is that treating depression, typically with prescription anti-depressants, doesn’t reliably translate into improved health behaviors, i.e. following diet better, etc., and may not improve blood sugar [12, 13, 14].
You may ask, why the paradox? Isn’t depression at the root of why I’m not taking care of myself as well as I could?
Evidence supports that techniques that address the fundamental emotions and behaviors appears to be effective.
This is a fair question, and I think the issue relates to how depression is treated. Evidence supports that techniques that address the fundamental emotions and behaviors appears to be effective. For example, cognitive behavioral therapy (CBT) appears to be effective at improving depression symptoms, blood sugar control and improves self-care . Simply put, CBT is a behavioral counseling technique that assists you in recognizing harmful thoughts and addressing them before these negative thoughts becoming negative actions.
More information about CBT, and a directory of providers, can be found on the Association for Behavioral and Cognitive Therapies (ABCT) website.
What are the natural treatment options for depression?
Although natural treatments have not been approved by the FDA for the treatment of depression, in my opinion, many of the natural treatments make more sense, especially for people with diabetes, than many of the prescription options available.
For example, does it make sense to prevent reuptake of serotonin, i.e. using a SSRI- or “selective serotonin reuptake inhibitor”, if the fundamental issue is not having enough serotonin to begin with? Because diabetes is known to be a condition of insulin deficiency, as well as insulin resistance, if the body cannot produce an adequate amount of insulin, it is feasible that tryptophan just does not enter the brain in adequate quantities. Preventing its reuptake may not do the trick if there isn’t enough around to start with!
Light boxes have been best studied in seasonal depression, or seasonal affective disorder (SAD), and are effective.
As briefly mentioned above, seasonal changes in sunlight normally impact mood and reduced serotonin availability leads to reduced mood and often and increased craving for carbohydrates [16, 17]. This is thought to be related to the reduction of vitamin D production which is regulated by the amount of sunlight that reaches your skin, and also by the amount of sunlight you literally see, i.e. the amount that goes through your eyes and tickles your optic nerve! Isn’t that amazing?!
Light boxes have been best studied in seasonal depression, or seasonal affective disorder (SAD), and are effective . In order to be effective, the light box has to be of sufficient strength (2000-10,000 lux - a unit of light intensity) for 30-120 minutes daily is required during the winter.
Interestingly, light boxes also appear to be effective for non-seasonal depression as well . This may be because vitamin D is such a common deficiency!
...vitamin D3 also appears to improve mood and regulate the production of serotonin.
As mentioned above, much of the seasonal variation in mood is attributable to reduced vitamin D levels (review Complementary Corner from March 2007 for more information on vitamin D in diabetes). Vitamin D3 has many hormone-like actions, including the regulation of calcium levels,but vitamin D3 also appears to improve mood and regulate the production of serotonin [20, 21]. Vitamin D3 deficiency is common in most latitudes, with prevalence estimates reaching 36% in the general population, and higher in people with diseases like diabetes [22, 23]. In my practice, granted it is in Seattle, WA, I would estimate 80-90% of my patients are vitamin D deficient.
Typical doses of vitamin D are 400-2000 IU per day. Ideally you would get your blood levels checked so that your replacement dose can be properly determined because not knowing your blood level may delay getting your levels back up to normal.
Vitamin B6, or pyridoxine, is an essential nutrient for the enzymes that synthesize many neurotransmitters including serotonin, dopamine, norepinephrine and gamma-aminobutyric acid (GABA) [24, 25]. Although not shown in humans, administering B6 to Rhesus monkeys (a primate with very similar neurobiology to humans) increased serotonin production in the brain . In rats, B6 increased production of serotonin precursor 5-hydroxytryptophan (5-HTP) .
Typical doses of vitamin B6 range from 1-20 mg, although doses of 3.5-5 mg are common in most “B-complex” vitamins and multivitamins.
Chromium is a mineral essential in human nutrition for the regulation of insulin sensitivity...
Chromium is a mineral essential in human nutrition for the regulation of insulin sensitivity, a hormone that regulates blood sugar levels in humans . Chromium has been extensively reviewed in diabetes. (Read Complementary Corner October 2006 for more information on chromium in diabetes.) Chromium picolinate (600 mcg/day) has been shown in human clinical trials to improve mood in some forms of depression, and to reduce carbohydrate craving [29, 30]. Chromium picolinate has demonstrated superior absorption than some other commonly available forms of chromium, e.g. chromium nicotinate .
Rhodiola is a botanical medicine used for stress and exhaustion. Rhodiola has been shown in human clinical trials to improve the capacity for work under stress, reduce the effects of reduced sleep on performance, improve physical energy during stress, and may improve symptoms of some forms of depression [32-35]. The mechanism of action appears to be the prolongation of neurotransmitters, including serotonin and dopamine, in the brain .
Rhodiola is a botanical medicine used for stress and exhaustion.
My clinical observations using Rhodiola for many years have been that low doses (<200mg per day) appear to be mildly energizing, whereas higher doses appear to be more relaxing and border on sedating. The reasons for this paradox, - higher doses being more calming - are unknown. Also, several patients have reported mild anxiety from using an alcohol extract, i.e. a tincture, of Rhodiola, whereas the whole, ground herb does not appear to cause this effect. This may be due to different herbal compounds being extracted by the alcohol in higher concentrations.
If you are taking prescription medication for depression, first talk with a doctor trained in nutritional medicine prior to starting 5-HTP...
Derived from the amino acid tryptophan, 5-HTP is an immediate precursor to serotonin production. The vast majority of well-designed clinical studies support the effectiveness of 5-HTP in treating numerous forms of clinical depression . 5-HTP is well absorbed from oral dosing, with up to 70% absorbed into the bloodstream for oral dosing [25, 37, 38].
Typical doses of 5-HTP are between 50-300 mg per day. Using 5-HTP in combination with other treatments may allow for lower doses. Although technically there are safety concerns about using 5-HTP in large doses or in combination with prescription anti-depressants, “serotonin syndrome” has not been reported due to 5-HTP, even in research studies that have used it in combination with medications . If you are taking prescription medication for depression, first talk with a doctor trained in nutritional medicine prior to starting 5-HTP in order to discuss the correct dose and how to monitor symptoms to ensure efficacy.
St. John’s Wort
St.John's Wort... may cause more harm than good in diabetes...
As mentioned above, St. John’s Wort, despite having some excellent clinical research support of efficacy in depression [39, 40], may cause more harm than good in diabetes because of the potential for drug interactions, including diabetes medications . I discourage taking St. John’s Wort, especially in patients taking “statin” medications such as Lipitor or Zocor for cholesterol because the interactions may impact the safety and effectiveness of the drug [42, 43].
Depression and diabetes co-exist very frequently, despite not clearly knowing which comes first. Depressive symptoms may impact healthy daily behaviors in diabetes, including following your diet, getting more exercise, and taking medications as recommended. Natural, pharmaceutical and counseling therapies are available for depression and are effective in reducing depression, and in some cases, improve healthy behaviors. Some natural treatments for depression may actually treat the cause of depression, e.g. vitamin D replacement, while others may also offset other common concerns in diabetes, e.g. chromium reducing carbohydrate cravings. Because depression and diabetes are a very serious combination, and because life is too short to be sad, if you think you are depressed, talk with your doctor and/or complementary health provider about appropriate treatment.
In health - Ryan Bradley, ND, MPH
Ryan Bradley, ND, MPH is a naturopathic doctor, clinical researcher and epidemiologist in San Diego, CA. In addition to his research, he is a practicing clinician specializing in natural and integrative approaches to treating type 2 diabetes, chronic kidney disease and heart disease at Pacific Pearl La Jolla.
1. Lam DD, Heisler LK. Serotonin and energy balance: molecular mechanisms and implications for type 2 diabetes. Expert Rev Mol Med. 2007;9(5):1-24.
2. NIMH. What are the signs and symptoms of depression? http://www.nimh.nih.gov/health/publications/depression/symptoms.shtml. Accessed 2-5-09, 2009.
3. Eaton WW. Epidemiologic evidence on the comorbidity of depression and diabetes. J Psychosom Res. Oct 2002;53(4):903-906.
4. Golden SH, Lee HB, Schreiner PJ, et al. Depression and type 2 diabetes mellitus: the multiethnic study of atherosclerosis. Psychosom Med. Jul-Aug 2007;69(6):529-536.
5. Saydah SH, Brancati FL, Golden SH, Fradkin J, Harris MI. Depressive symptoms and the risk of type 2 diabetes mellitus in a US sample. Diabetes Metab Res Rev. May-Jun 2003;19(3):202-208.
6. Golden SH, Williams JE, Ford DE, et al. Depressive symptoms and the risk of type 2 diabetes: the Atherosclerosis Risk in Communities study. Diabetes Care. Feb 2004;27(2):429-435.
7. Gallo JJ, Bogner HR, Morales KH, Post EP, Ten Have T, Bruce ML. Depression, cardiovascular disease, diabetes, and two-year mortality among older, primary-care patients. Am J Geriatr Psychiatry. Sep 2005;13(9):748-755.
8. Selby JV, Swain BE, Gerzoff RB, et al. Understanding the gap between good processes of diabetes care and poor intermediate outcomes: Translating Research into Action for Diabetes (TRIAD). Med Care. Dec 2007;45(12):1144-1153.
9. Park H, Hong Y, Lee H, Ha E, Sung Y. Individuals with type 2 diabetes and depressive symptoms exhibited lower adherence with self-care. J Clin Epidemiol. Sep 2004;57(9):978-984.
10. Gonzalez JS, Safren SA, Cagliero E, et al. Depression, self-care, and medication adherence in type 2 diabetes: relationships across the full range of symptom severity. Diabetes Care. Sep 2007;30(9):2222-2227.
11. Paile-Hyvarinen M, Wahlbeck K, Eriksson JG. Quality of life and metabolic status in mildly depressed women with type 2 diabetes treated with paroxetine: a single-blind randomised placebo controlled trial. BMC Fam Pract. May 14 2003;4:7.
12. Katon WJ, Von Korff M, Lin EH, et al. The Pathways Study: a randomized trial of collaborative care in patients with diabetes and depression. Arch Gen Psychiatry. Oct 2004;61(10):1042-1049.
13. Lin EH, Katon W, Rutter C, et al. Effects of enhanced depression treatment on diabetes self-care. Ann Fam Med. Jan-Feb 2006;4(1):46-53.
14. Williams JW, Jr., Katon W, Lin EH, et al. The effectiveness of depression care management on diabetes-related outcomes in older patients. Ann Intern Med. Jun 15 2004;140(12):1015-1024.
15. Lustman PJ, Griffith LS, Freedland KE, Kissel SS, Clouse RE. Cognitive behavior therapy for depression in type 2 diabetes mellitus. A randomized, controlled trial. Ann Intern Med. Oct 15 1998;129(8):613-621.
16. Harmatz MG, Well AD, Overtree CE, Kawamura KY, Rosal M, Ockene IS. Seasonal variation of depression and other moods: a longitudinal approach. J Biol Rhythms. Aug 2000;15(4):344-350.
17. Wurtman RJ, Wurtman JJ. Brain serotonin, carbohydrate-craving, obesity and depression. Obes Res. Nov 1995;3 Suppl 4:477S-480S.
18. Magnusson A, Boivin D. Seasonal affective disorder: an overview. Chronobiol Int. Mar 2003;20(2):189-207.
19. Tuunainen A, Kripke DF, Endo T. Light therapy for non-seasonal depression. Cochrane Database Syst Rev. 2004(2):CD004050.
20. Lansdowne AT, Provost SC. Vitamin D3 enhances mood in healthy subjects during winter. Psychopharmacology (Berl). Feb 1998;135(4):319-323.
21. Partonen T. Vitamin D and serotonin in winter. Med Hypotheses. Sep 1998;51(3):267-268.
22. Park S, Johnson MA. Living in low-latitude regions in the United States does not prevent poor vitamin D status. Nutr Rev. Jun 2005;63(6 Pt 1):203-209.
23. Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc. Mar 2006;81(3):353-373.
24. Dakshinamurti K, Paulose CS, Viswanathan M, Siow YL, Sharma SK, Bolster B. Neurobiology of pyridoxine. Ann N Y Acad Sci. 1990;585:128-144.
25. Turner EH, Loftis JM, Blackwell AD. Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. Pharmacol Ther. Mar 2006;109(3):325-338.
26. Hartvig P, Lindner KJ, Bjurling P, Laengstrom B, Tedroff J. Pyridoxine effect on synthesis rate of serotonin in the monkey brain measured with positron emission tomography. J Neural Transm Gen Sect. 1995;102(2):91-97.
27. Calderon-Guzman D, Hernandez-Islas JL, Espitia-Vazquez I, et al. Pyridoxine, regardless of serotonin levels, increases production of 5-hydroxytryptophan in rat brain. Arch Med Res. Jul-Aug 2004;35(4):271-274.
28. Anderson RA. Chromium as an essential nutrient for humans. Regul Toxicol Pharmacol. Aug 1997;26(1 Pt 2):S35-41.
29. Docherty JP, Sack DA, Roffman M, Finch M, Komorowski JR. A double-blind, placebo-controlled, exploratory trial of chromium picolinate in atypical depression: effect on carbohydrate craving. J Psychiatr Pract. Sep 2005;11(5):302-314.
30. Davidson JR, Abraham K, Connor KM, McLeod MN. Effectiveness of chromium in atypical depression: a placebo-controlled trial. Biol Psychiatry. Feb 1 2003;53(3):261-264.
31. Anderson RA, Polansky MM, Bryden NA. Stability and absorption of chromium and absorption of chromium histidinate complexes by humans. Biol Trace Elem Res. Dec 2004;101(3):211-218.
32. Darbinyan V, Aslanyan G, Amroyan E, Gabrielyan E, Malmstrom C, Panossian A. Clinical trial of Rhodiola rosea L. extract SHR-5 in the treatment of mild to moderate depression. Nord J Psychiatry. 2007;61(5):343-348.
33. Darbinyan V, Kteyan A, Panossian A, Gabrielian E, Wikman G, Wagner H. Rhodiola rosea in stress induced fatigue--a double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty. Phytomedicine. Oct 2000;7(5):365-371.
34. Shevtsov VA, Zholus BI, Shervarly VI, et al. A randomized trial of two different doses of a SHR-5 Rhodiola rosea extract versus placebo and control of capacity for mental work. Phytomedicine. Mar 2003;10(2-3):95-105.
35. Spasov AA, Wikman GK, Mandrikov VB, Mironova IA, Neumoin VV. A double-blind, placebo-controlled pilot study of the stimulating and adaptogenic effect of Rhodiola rosea SHR-5 extract on the fatigue of students caused by stress during an examination period with a repeated low-dose regimen. Phytomedicine. Apr 2000;7(2):85-89.
36. Stancheva SL MA. Effect of the extract Rhodiola rosease L. on the content of the brain biogenic monoamines. . Med Physiol. 1987;40:85-87.
37. Magnussen I, Jensen TS, Rand JH, Van Woert MH. Plasma accumulation of metabolism of orally administered single dose L-5-hydroxytryptophan in man. Acta Pharmacol Toxicol (Copenh). Sep 1981;49(3):184-189.
38. Magnussen I, Van Woert MH. Human pharmacokinetics of long term 5-hydroxytryptophan combined with decarboxylase inhibitors. Eur J Clin Pharmacol. 1982;23(1):81-86.
39. Kasper S, Gastpar M, Muller WE, et al. Efficacy of St. John's wort extract WS 5570 in acute treatment of mild depression: a reanalysis of data from controlled clinical trials. Eur Arch Psychiatry Clin Neurosci. Feb 2008;258(1):59-63.
40. Rahimi R, Nikfar S, Abdollahi M. Efficacy and tolerability of Hypericum perforatum in major depressive disorder in comparison with selective serotonin reuptake inhibitors: A meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. Feb 1 2009;33(1):118-127.
41. Xu H, Williams KM, Liauw WS, Murray M, Day RO, McLachlan AJ. Effects of St John's wort and CYP2C9 genotype on the pharmacokinetics and pharmacodynamics of gliclazide. Br J Pharmacol. Apr 2008;153(7):1579-1586.
42. Andren L, Andreasson A, Eggertsen R. Interaction between a commercially available St. John's wort product (Movina) and atorvastatin in patients with hypercholesterolemia. Eur J Clin Pharmacol. Oct 2007;63(10):913-916.
43. Eggertsen R, Andreasson A, Andren L. Effects of treatment with a commercially available St John's Wort product (Movina) on cholesterol levels in patients with hypercholesterolemia treated with simvastatin. Scand J Prim Health Care. Sep 2007;25(3):154-159.
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