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An Orthomolecular Approach to Mental Health

Posted September 18, 2018

By: Dr. Colin O’Brien ND, Medical Doctor, Cyto-Matrix

Depression and anxiety are conditions that affect us all, either personally or through the suffering of friends, family and patients.  While there are a seemingly endless number of factors to consider that are unique to each individual, one area that should always be addressed is nutritional status.

Anecdotal evidence and clinical research has shown us that mental health concerns can arise in the presence of single or multiple nutrient deficiencies. Here is a brief summary of some of the most common nutrients to consider when treating mental health:

 

Magnesium: Although we typically associate magnesium with musculoskeletal function, it has been shown to increase brain-derived neurotrophic factor (BDNF) and GABA, while down-regulating ACTH and blocking NMDA receptors. Benefits for improving depression markers have been seen with supplementation after only 1-2 weeks in many different forms (such as oxide, glycinate and taurinate). Although clinical trials have shown benefits for depression and anxiety between 125-300mg of elemental magnesium per day, clinically it may be most useful to dose to bowel tolerance.

 

Zinc: The hippocampus, the area of the brain responsible for emotion, memory and motivation, has one of highest concentrations of zinc in the body. Many studies have shown that lower zinc levels are associated with depression, and interventional trials support its use for this purpose. Specifically, zinc sulphate has successfully been used in Multiple Sclerosis patients and zinc gluconate has been used in obese patients, with both improving Beck Depression scores after 12 weeks. The evidence based dose is 25-50mg of elemental zinc per day and zinc supplementation can also safely improve SSRI outcomes.

 

B-vitamins: A 2015 Systematic Review found that B12 and Folate reduced the onset and relapse risk for depression with long-term supplementation. Similarly, a combination of 500mcg vitamin B12, 2mg Folate and 25mg vitamin B6 has been shown to improve antidepressant medication response over a full year. Clinically, a well-balanced B-complex supplement or intramuscular methylcobalamin and folate injections can have an immediate positive impact on mood and energy, if patients have suboptimal levels. I prefer my mental health patient’s serum B12 levels to be above 500 pmol/L.

 

Iron: Iron is not only needed for hemoglobin synthesis, but also serotonin production and the proper conversion of thyroxine (T4) to triiodothyronine (T3). Although no interventional studies have been done with iron and depression or anxiety, there is a strong and convincing correlation noted between low hemoglobin and depression with a dose-response relationship, meaning those with worse anemia demonstrate more severe depression. Ferritin levels below 45 ng/mL and hemoglobin below 120 g/L for women (less than 130 g/L for men) are associated with depressive symptoms

 

Vitamin D: Higher serum levels have been associated with a 43% lower risk of depression and panic disorder, with various interventional trials showing benefits for depression with a wide range of dosing (ie 50,000 IU/week vs. 2,000 IU/day). Similarly, benefits for vitamin D supplementation in depressed adolescent females, obese populations and perinatal mothers has been demonstrated. However, there are also many interventional trials showing lack of benefit which could be due to adequate vitamin D status in subjects at baseline. The target blood levels for optimal mood should be 75 nmol/L or greater.

 

Omega-3’s: A 2018 analysis of 19 RCTs found that fish oil supplementation provided a modest improvement in those with anxiety, with a greater effect in those taking more than 2,000mg/day of combined EPA and DHA. When it comes to depression, some evidence has shown that it is not beneficial to simply restore polyunsaturated fatty acid (PUFA) status in the body, but rather that omega-3’s can be beneficial in cases of systemic inflammation. In fact, your depressed patients are most likely to respond to omega-3 supplementation if their high sensitivity C-reactive protein (hs-CRP) is above 3.0. The evidence based dosage in depression is 1000-2000mg of EPA per day.

 

Selenium: Time to eat those brazil nuts! There are at least 5 studies associating low selenium with depression & anxiety, while one interventional study of 100mcg/day improved mood after only 5 weeks.

 

When it comes to choosing the right nutrient(s) for supplementation, lab testing, clinical signs and symptoms, and knowledge of common medication depletions should be considered. But the take home message from all of this should be that, when it comes to mental health, diet matters…a lot. There are many nutrients necessary to keep the brain balanced.

Perhaps the best study to illustrate this was the 2017 RCT of 67 individuals with moderate to severe depression. After 12-weeks of eating a modified Mediterranean diet, 32% went into remission compared to only 8% of the control group. The key here is that the dietary intervention was ad libitum, meaning the focus was on food quality and not calories. The group was even allowed up to 3 servings per week of “extras” such as refined sugars, alcoholic drinks and fast-foods, showing that it doesn’t need to be an “all-or-none” approach.

Even encouraging patients to “Eat the rainbow” to get a wide variety of nutrients and to focus on “Eating whole foods” to reduce sugars and additives is often an easy starting point for many individuals that feel overwhelmed with dietary changes. In fact, simply reducing the glycemic index of foods can reduce the risk for depression.

When it comes to mental health, part of the solution for our patients may be simpler than we think. In the words of Michael Pollan, “Eat real food. Not too much. Mostly plants.”

 


 

References:

[1]  Tarleton EK, Littenberg B, MacLean CD, Kennedy AG, Daley C (2017) Role of magnesium supplementation in the treatment of depression: A
randomized clinical trial. PLoS ONE 12(6).

[2]  Rajizadeh, Afsaneh et al. Effect of magnesium supplementation on depression status in depressed patients with magnesium deficiency: A
randomized, double-blind, placebo-controlled trial. Nutrition, Volume 35, 56 – 60.

[3]  Eby GA, Eby KL. Rapid recovery from major depression using magnesium treatment. Med Hypotheses. 2006;67(2):362-70. Epub 2006 Mar 20.

[4]  Levenson CW. Zinc: the new antidepressant? Nutr Rev. 2006 Jan;64(1):39-42.

[5] Salari S et al. Zinc sulphate: A reasonable choice for depression management in patients with multiple sclerosis: A randomized, double-blind,
placebo-controlled clinical trial. Pharmacol Rep. 2015 Jun;67(3):606-9.

[6] Solati Z et al. Zinc monotherapy increases serum brain-derived neurotrophic factor (BDNF) levels and decreases depressive symptoms in
overweight or obese subjects: a double-blind, randomized, placebo-controlled trial. Nutr Neurosci. 2015 May;18(4):162-8.

[7] Nowak G, Szewczyk B, Pilc A. Zinc and depression. An update. Pharmacol Rep. 2005 Nov-Dec;57(6):713-8.

[8]Almeida OP, Ford AH and Flicker L. Systematic review and meta-analysis of randomized placebo-controlled trials of folate and vitamin
B12 for depression. Int Psychogeriatr. 2015 May;27(5):727-37.

[9] Almeida OP, Ford AH, Hirani V, Singh V, vanBockxmeer FM, McCaul K, Flicker L. B vitamins to enhance treatment response to antidepressants in
middle-aged and older adults: results from the B-VITAGE randomised, double-blind, placebo-controlled trial. Br J Psychiatry. 2014 Sep 25.

[10] Vulser H et al. Association between depression and anemia in otherwise healthy adults. Acta Psychiatr Scand. 2016 Aug;134(2):150-60.

[11] Stewart R and Hirani V. Relationship between depressive symptoms, anemia, and iron status in older residents from a national survey
population. Psychosom Med. 2012 Feb-Mar;74(2):208-13.

[12] Maddock J, Berry DJ, Geoffroy MC, Power C, Hypponen E. Vitamin D and common mental disorders in mid-life: cross-sectional and prospective
findings. Clin Nutr. 2013 Jan 21.

[13] Bahrami A et al. High Dose Vitamin D Supplementation Is Associated With a Reduction in Depression Score Among Adolescent Girls: A Nine-
Week Follow-Up Study. J Diet Suppl. 2017 Jul 31:1-10.

[14] Vaziri F et al. A randomized controlled trial of vitamin D supplementation on perinatal depression: in Iranian pregnant mothers. BMC
Pregnancy Childbirth. 2016 Aug 20;16:239.

[15] Jorde R et al. Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind
trial. J Intern Med. 2008 Dec;264(6):599-609.

[16] Gowda U et al. Vitamin D supplementation to reduce depression in adults: meta-analysis of randomized controlled trials. Nutrition. 2015
Mar;31(3):421-9.

[17] Su K, Tseng P, Lin P, et al. Association of Use of Omega-3 Polyunsaturated Fatty Acids With Changes in Severity of Anxiety Symptoms: A
Systematic Review and Meta-analysis. JAMA Network Open.2018;1(5):e182327. doi:10.1001/jamanetworkopen.2018.2327.

[18] Appleton KM, Gunnell D, Peters TJ, Ness AR, Kessler D, Rogers PJ. No clear evidence of an association between plasma concentrations of n-3
long-chain polyunsaturated fatty acids and depressed mood in a non-clinical population. Prostaglandins Leukot Essent Fatty Acids. 2008
Jun;78(6):337-42.

[19] Rapaport MH et al. Inflammation as a predictive biomarker for response to omega-3 fatty acids in major depressive disorder: a proof-of-
concept study. Mol Psychiatry. 2016 Jan;21(1):71-9.

[20] Benton D. Selenium intake, mood and other aspects of psychological functioning. Nutr Neurosci. 2002 Dec;5(6):363-74.

Rethinking Protein Supplementation in your Practice

Posted August 20, 2018

By: Dr. Colin O’Brien ND, Medical Doctor, Cyto-Matrix

It’s easy to think of protein supplementation when patients are concerned about athletic performance and muscle recovery. Of course, protein is extremely useful in these circumstances, yet the many other clinical indications often get overlooked. Protein is a macronutrient that should be considered as a foundational item in all of our treatment protocols.

Improving dietary protein intake is key. But many times, a high-quality protein supplement is useful adjunctively. The purpose of this article is not to say that everyone should be supplementing with protein, more so, to say that there are likely other circumstances that you could be considering its impact. Here is a brief refresher on when to consider a high-quality protein with your patients:

 

  • Liver Health: Whey protein is a rich source of cysteine, making it a viable option to increase glutathione production and, therefore, liver detoxification. Research has confirmed this and also shown that protein supplementation improves outcomes in individuals with liver cirrhosis and those with non-alcoholic steatohepatitis (NASH).[1] [2]
  • Blood Sugar Regulation: Protein, unlike carbohydrates, does not significantly raise blood sugars in individuals with adequate insulin levels.[3] In fact, substituting protein in for carbohydrates or other macronutrients may lead to better blood sugar regulation in both diabetics[4] and non-diabetics.[5]  
  • Pre-eclampsia: Weak evidence suggests that the edema and protein spilling in pre-eclampsia is as a result of low protein intake, breaking down tissues to provide the fetus with needed amino acids. Although research appears to be far from conclusive, extra protein is a simple and safe intervention.[6]
  • Weight Management: High protein meals, especially at breakfast, have been shown to increase satiety and reduce snacking, making protein supplementation a staple for those trying to lose weight or manage dietary cravings.[7] [8]
  • Post-surgery Recovery: Regardless of the complexity or invasiveness of the procedure, surgery is a significant stress and physical trauma to the body. This means that protein is required for recovery. Evidence shows that protein is beneficial not only on the days after surgery but also in preparation for the operation.[9] [10]
  • Hair Loss: Yes, thyroid function, iron, biotin, medication side effects and other factors need to be considered for hair loss, but protein is a core component of collagen and a core component of hair. Most women trying to solve hair loss on their own likely don’t consider protein levels as a key first step.[11]
  • Sports Performance: It is still worth mentioning that protein supplementation added to a resistance training or endurance program has the ability to stimulate anabolism in muscles with increased hypertrophy, improved strength and reduced recovery time.[12] [13]
  • Bone Health: Protein is necessary for building collagen in the bone matrix. Multiple studies have shown that protein supplementation improves fracture healing, bone mineral density and overall recovery from injury.[14] [15]
  • Mood Balancing: Protein contains all the amino acid building blocks for our key neurotransmitters like dopamine, GABA and serotonin. Moreover, anecdotal and preliminary evidence shows that specific amino acids, like taurine, can be beneficial for balancing mood.[16] A common concern in poorly managed vegan or vegetarian patients is low mood, and suboptimal protein intake can be a part of this problem in conjunction with low iron and B12.

 

Certainly, this is not an all-encompassing list of reasons to consider protein supplementation with your patients, but it should serve as a reminder, at the very least, to assess macronutrient intake and be cognizant of the tremendous impact that suboptimal protein intake can have on the body long-term!


References:

[1] Hirsch S et al. Nutritional support in alcoholic cirrhotic patients improves host defenses. J Am Coll Nutr. 1999 Oct;18(5):434-41.

[2] Chitapanarux T et al. Open-labeled pilot study of cysteine-rich whey protein isolate supplementation for nonalcoholic steatohepatitis patients. J Gastroenterol Hepatol. 2009 Jun;24(6):1045-50. doi: 10.1111/j.1440-1746.2009.05865.x.

[3] Franz MJ. Protein: metabolism and effect on blood glucose levels. Diabetes Educ. 1997 Nov-Dec;23(6):643-6, 648, 650-1.

[4] Mary C Gannon, Frank Q Nuttall, Asad Saeed, Kelly Jordan, Heidi Hoover; An increase in dietary protein improves the blood glucose response in persons with type 2 diabetes, The American Journal of Clinical Nutrition, Volume 78, Issue 4, 1 October 2003, Pages 734–741, https://doi.org/10.1093/ajcn/78.4.734

[5] Rains TM et al. A randomized, controlled, crossover trial to assess the acute appetitive and metabolic effects of sausage and egg-based convenience breakfast meals in overweight premenopausal women. Nutr J. 2015 Feb 10;14:17. doi: 10.1186/s12937-015-0002-7.

[6] James M. Roberts, Judith L. Balk, Lisa M. Bodnar, José M. Belizán, Eduardo Bergel, Anibal Martinez; Nutrient Involvement in Preeclampsia, The Journal of Nutrition, Volume 133, Issue 5, 1 May 2003, Pages 1684S–1692S, https://doi.org/10.1093/jn/133.5.1684S

[7] Heather J Leidy, Laura C Ortinau, Steve M Douglas, Heather A Hoertel; Beneficial effects of a higher-protein breakfast on the appetitive, hormonal, and neural signals controlling energy intake regulation in overweight/obese, “breakfast-skipping,” late-adolescent girls, The American Journal of Clinical Nutrition, Volume 97, Issue 4, 1 April 2013, Pages 677–688, https://doi.org/10.3945/ajcn.112.053116

[8] Skov AR et al. Randomized trial on protein vs carbohydrate ad libitum fat reduced diet for the treatment of obesity. Int J Obes 1999; 23:528-536

[9] Herbert Freund et al. Infusion of the Branched Chain Amino Acids in Postoperative Patients: Anticatabolic Properties. Ann Surg. 1979 Jul; 190(1): 18–23.

[10] Klein JD et al. Perioperative nutrition and postoperative complications in patients undergoing spinal surgery. Spine (Phila Pa 1976). 1996 Nov 15;21(22):2676-82.

[11] Rushton DH. Nutritional factors and hair loss. Clin Exp Dermatol. 2002 Jul;27(5):396-404.

[12] Cooke et al. Whey protein isolate attenuates strength decline after eccentrically-induced muscle damage in healthy individuals. J Int Soc Sports Nutr. 2010 Sep 22;7:30. doi: 10.1186/1550-2783-7-30.

[13] Cermak et al. Protein supplementation augments the adaptive response of skeletal muscle to resistance-type exercise training: a meta-analysis. Am J Clin Nutr. 2012 Dec;96(6):1454-64. doi: 10.3945/ajcn.112.037556. Epub 2012 Nov 7.

[14] Chiu JF, Lan SJ, Yang CY, Wang PW, Yao WJ, Su LH, Hsieh CC. Long-term vegetarian diet and bone mineral density in postmenopausal Taiwanese women. Calcif Tissue Int. 1997 Mar;60(3):245-9.

[15] Tengstrand B et al. Effects of protein-rich supplementation and nandrolone on bone tissue after a hip fracture. Clin Nutr. 2007 Aug;26(4):460-5. Epub 2007 May 11.

[16] Gao-Feng Wu et al. Antidepressant effect of taurine in chronic unpredictable mild stress-induced depressive rats. Sci Rep. 2017; 7: 4989. Published online 2017 Jul 10.

The Role of Antioxidants in Sun Protection

Posted July 5, 2018

By: Dr. Colin O’Brien ND, Medical Director, Cyto-Matrix

The sun is shining and summer is officially here! This is great news for many of us Canadians that find the winters to always be a bit too long…but it’s not so great for our skin health if we aren’t well prepared.

Proper sunscreen application, skin coverage and avoidance of direct sun during peak UV hours (11am-3pm) are all important factors when it comes to sun safety and reducing your risk of sunburn and skin cancer. But few people acknowledge the role of diet and antioxidant protection in sun protection. What we put in our bodies matters, too.

For example, excessive alcohol consumption has been correlated with higher rates of sunburn, and interventional evidence confirms that alcohol consumption reduces the time it takes for your skin to become red after UV exposure. Essentially, alcohol decreases the efficiency of our antioxidant network in the skin, thereby decreasing the protection from UV rays. Not such great news for patio beers and summer drinks on the dock.

This all makes sense, though, when you consider that tanning or becoming sunburnt is simply damage caused by ultraviolet rays. Our skin darkens to naturally protect against future exposure to these same UV rays. As this process is occurring, tons of free radicals are produced in the body that need to be quenched. Antioxidants to the rescue!

In addition to a diet high in antioxidants and bioflavonoids from fruits and vegetables, specific natural health ingredients have been targeted and identified as beneficial for sun protection. Consider the following antioxidants for extra support:

 

  • Cocoa: As if you need more reason to consume regular amounts of dark chocolate, research has shown that a daily cocoa powder drink led to less redness after UV exposure at 6 and 12 weeks. Improved hydration and circulation of the skin was also noted in those consuming the flavanol-dense cocoa drink but not those in the control group.
  • Vitamin C and E: Multiple studies have explored the effects of these commonplace anti-oxidants in UV protection. It turns out that both topical application of vitamin C and oral supplementation of vitamin C in combination with vitamin E can provide numerous benefits. One study explored an oral combination of vitamin C, vitamin E, selenium, carotenoids and proanthocyanidins, finding that the blend led to a decrease in matrix metalloprotease levels after UV exposure, possibly explaining part of the mechanism involved in antioxidant photoprotection.
  • Carotenoids: Various carotenoids, alone and in combination, have shown promise for UV protection. A double-blind placebo-controlled trial of 20 women found that 30mg of beta-carotene per day, for 10 weeks prior to 13 days of sun exposure, led to less skin redness. Another study of 24mg of Beta-Carotene, in combination with 8mg Lutein and 8mg Lycopene showed benefit. A combination of lutein and zeaxanthan, orally and topically, also show benefits. Two poorly done studies found that mixed carotenoids allowed for greater tolerability of the sun and more time until redness ensued. It should be noted that other studies have found limited or no benefit for sun protection with carotenoids, but the vast majority show benefits.
  • Green Tea Extract: Although animal research and human study have only shown benefits for the topical application of green tea and its constituents, it stands to reason that regular oral consumption of the anti-oxidant powerhouse tea would be a good idea for the prevention and treatment of sun damage, too. At the very least, daily intake of green tea can be used to promote optimal metabolism and perhaps replace other bad habits!
  • EPA Omega-3 Fatty Acid: In a double-blind randomized study, either 4 grams/day of EPA or 4 grams/day of oleic acid was supplemented for 3 months. After 3 months of supplementation, those in the EPA group had an 8-fold increase in EPA skin content and, most importantly, significantly reduced sunburn sensitivity (meaning a greater resiliency or threshold until burning). Markers of DNA damage in the skin were also reduced.  

 

Animal research, anecdotal evidence and mechanistic data suggests that there are many other antioxidants to consider for UV protection of the skin such as astaxanthin, CoQ10 and resveratrol. Preliminary research also indicates that nicotinamide, a form of vitamin B3, is photoprotecive as well, and that quercetin and rutin may be effective when used topically. The recurring theme is antioxidant support and it seems that a blend is best. If you’re headed to the beach, be sure to get your fruits and veggies in!

A Final Note on Sunscreens: When it comes to sunscreens, it is important to mention that they are not all created equal. Here is a quick summary of what to look for in a sunscreen:

  1. Avoid retinyl palmitate and oxybenzone, as these compounds have been associated with hormone disruption and carcinogen activity
  2. Ensure there are active ingredients such as zinc oxide, titanium oxide, avobenzone and mexoryl SX.
  3. Choose lotions instead of sprays

Check out the Environmental Working Group (ewg.org) for more info.


References: 

[1] Mukamal KJ. Alcohol consumption and self-reported sunburn: a cross-sectional, population-based survey. J Am Acad
Dermatol. 2006 Oct; 55(4): 584-9.
[2] Darvin ME et al. Alcohol consumption decreases the protection efficiency of the antioxidant network and increases the risk of
sunburn in human skin. Skin Pharmacol Physiol.2013; 26(1): 45-51.
[3] Heinrich U, Neukam K, Tronnier H et al. Long-term ingestion of high flavanol cocoa provides photoprotection against UV-induced
erythema and improves skin condition in women.J Nutr.2006;136:1565-1569
[4] Traikovich SS. Use of topical ascorbic acid and its effects on photodamaged skin topography.Arch Otolaryngol Head Neck
Surg.1999;125:1091-1098.
[5] Eberlein-Konig B, Placzek M, Przybilla B. Protective effect against sunburn of combined systemic ascorbic acid (vitamin C) and d-
alpha-tocopherol (vitamin E).J Am Acad Dermatol. 1998;38:45-48.
[6] Fuchs J, Kern H. Modulation of UV-light-induced skin inflammation by D-alpha-tocopherol and L-ascorbic acid: a clinical study using
solar simulated radiation.Free Radic Biol Med.1998;25:1006-1012.
[7] Greul AK, Grundmann JU, Heinrich F, et al. Photoprotection of UV-irradiated human skin: an antioxidative combination of vitamins
E and C, carotenoids, selenium, and proanthocyanidins.Skin Pharmacology and AppliedSkin Physiology.2002;15:307-315.
[8] Gollnick HPM, Hopfenmuller W, Hemmes C, et al. Systemic beta carotene plus topical UV sunscreen are an optimal protection
against harmful effects of natural UV-sunlight: results of the Berlin-Eilath study.Eur J Dermatol. 1996;6:200-205.
[9] Heinrich U, Gartner C, Wiebusch M, et al. Supplementation with beta-carotene or a similar amount of mixed carotenoids protects
humans from UV-induced erythema.J Nutr. 2003;133:98-101.
[10] Palombo P, Fabrizi G, Ruocco V, et al. Beneficial long-term effects of combined oral/topical antioxidant treatment with the
carotenoids lutein and zeaxanthin on human skin: a double-blind, placebo-controlled study.Skin Pharmacol Physiol.2007;20:199-
210.
[11] Lee J, Jiang S, Levine N, et al. Carotenoid supplementation reduces erythema in human skin after simulated solar radiation
exposure.Proc Soc Exp Biol Med. 2000; 223:170-174.
[12] Stahl W, Heinrich U, Jungmann H, et al. Carotenoids and carotenoids plus vitamin E protect against ultraviolet light-induced
erythema in humans.Am J Clin Nutr. 2000;71:795-798.
[13] Garmyn M, Ribaya-Mercardo JD, Russel RM, et al. Effect of beta-carotene supplementation on the human sunburn reaction.Exp
Dermatol.1995;4:104-111.
[14] Katiyar SK, Elmets CA, Agarwal R, et al. Protection against ultraviolet-B radiation-induced local and systemic suppression of contact
hypersensitivity and edema responses in C3H/HeN mice by green tea polyphenols.Photochem Photobiol.1995;62:855-861.
[15] Elmets CA, Singh D, Tubesing K, et al. Cutaneous photoprotection from ultraviolet injury by green tea polyphenols.J Am Acad
Dermatol.2001;44:425-432
[16] Lesley E. et al. Effect of eicosapentaenoic acid, an omega-3 polyunsaturated fatty acid, on UVR-related cancer risk in humans. An
assessment of early genotoxic markers,Carcinogenesis Vol 24(5); 2003: 919–925.

[17] Damian DL. Photoprotective effects of nicotinamide. Photochem Photobiol Sci.2010 Apr;9(4):578-85.
[18] Choquenet B et al. Quercetin and rutin as potential sunscreen agents: determination of efficacy by an in vitro method. J Nat
Prod.2008 Jun; 71(6): 1117-8.

Lesser-Known and Broad-Reaching Effects of Iron Deficiency

Posted May 1, 2018

By: Dr. Colin O’Brien ND, Medical Director, Cyto-Matrix

Every healthcare practitioner should be able to rhyme off the keynote symptoms of iron-deficiency: fatigue, weakness, dizziness and pallor (pale skin) probably come to mind first. This makes sense given that iron is the most commonly deficient nutrient in the world and a concern often seen in private practice. But the implications of suboptimal iron extend much further than low hemoglobin and low energy. Iron is needed for so much more.

Many practitioners, myself included, have likely missed opportunities to successfully treat patients with iron restoration therapies over the years because of more “atypical” signs and symptoms of inadequate iron. Yes, iron is classically needed in hemoglobin formation and, therefore, oxygen delivery and energy levels, but here are some other conditions and physiological functions that may warrant a more thorough exploration of iron levels:

 

Restless Leg Syndrome (RLS): Iron deficiency has been found to be a common cause of RLS occurring in about 25% of cases! Supplemental iron is certainly most effective in those with documented iron deficiency, however, some patients respond to iron supplementation even without anemia. Iron is thought to be beneficial for RLS through its ability to upregulate dopamine synthesis (it is needed to convert tyrosine into dopamine). If the RLS is refractory to iron therapy, consider deficiencies of magnesium, B12 and vitamin E instead.

 

Female Infertility: Case reports have found that iron supplementation resulted in pregnancy within 28 weeks in infertile woman with borderline low ferritin levels (14-40 ng/mL). Certainly, this is not to say that iron is the ‘silver bullet’ for female infertility, but it deserves attention amidst all other factors.

 

Diffuse Hair Loss: General hair loss can be a symptom of iron deficiency, even before anemia sets in. Restoring optimal iron levels has been shown to offset this symptom and iron supplementation can also be useful in cases of brittle, dry and splitting hairs (if you’re having compliance issues with iron supplements in iron-deficient female patients, this may be worth mentioning!)

 

Poor Immune function: Iron is needed for proper immune function through cytokine production in macrophages and an iron-deficient state may lead to an insufficient immune response. For example, one study in individuals with oral candidiasis found that iron restoration led to lower salivary candida counts and reduced oral lesions.

 

Thyroid Function: We classically discuss the need for selenium to convert T4 into the more bioactive T3, but iron is another mineral that is necessary to promote this conversion through deiodinase activity (and iron is also needed for thyroid peroxidase action). To make matters worse, low thyroid function can lead to worse iron absorption. In cases of hypothyroidism with concomitant iron deficiency, combination treatment with iron and levothyroxine has been shown to be superior over each therapy alone.

 

Menorrhagia (heavy menstrual bleeding): Substantial blood loss can obviously lead to iron deficiency. However, few people are aware that an iron deficiency can actually cause a recurring state of heavy menstrual bleeding through weakened uterine muscles that cannot properly clamp down on blood vessels (iron is a cofactor for cytochrome oxidase, an enzyme necessary for muscle contraction). Ultimately, interventional trials confirm that iron supplementation is necessary not only for symptom control but also to reduce the heavy bleeding itself.

 

Cognition, Mood & Intelligence: It is well-documented that children and adults perform poorer on mental function tests in states of iron deficiency, with areas such as attention, memory and concentration being affected. This is the case even in the absence of outright anemia. Mechanistically, inadequate iron supply leads to a dysregulation of dopamine and serotonin metabolism. Both animal trials and human studies have shown that severe iron deficiency during infancy may have long-standing implications on brain health that persist well into adulthood, regardless of adequate iron intake later on in life.

 

As clinicians, it is easy to start down a rabbit-hole to find a medical explanation for complex issues. Yet, it’s generally best to follow the principle of ‘Occam’s razor’: the simplest solution is typically the correct solution. If a patient is vegan, has heavy bleeding or any of the conditions listed above, get back to the basics and test their hemoglobin, ferritin and other blood markers. A well-absorbed iron might be the simple answer that you and your patients are looking for. 

 

Select References:

  1. Earley, C. J. (2009). The importance of oral iron therapy in restless legs syndrome. Sleep Medicine, 10(9), 945-946.
  2. Rushton DH, Ramsay ID, Gilkes JJH, Norris MJ. Ferritin and Fertility. Lancet 1991; 337:1554.
  3. Hard S. Non-anemic iron deficiency as an etiological factor in diffuse loss of hair of the scalp in women. Acta Derm Venereol 1963; 43:562-569.
  4. Sato S. Iron deficiency : structural and microchemical changes in hair, nails and skin. Semin Dermatol 1991; 10:313-319.
  5. Ganz T, Nemeth E. Iron homeostasis in host defence and inflammation. Nat Rev Immunol. 2015 Aug;15(8):500-10.
  6. Higgs JM. Chronic mucocutaneous candidiasis: iron deficiency and the effects of iron therapy. Proc R Soc Med 1973; 66:802-804.
  7. Soliman AT, De Sanctis V, Yassin M, Wagdy M, Soliman N. Chronic anemia and thyroid function. Acta Biomedica. 2017 Apr 28;88(1):119-127.
  8. Ravanbod M, Asadipooya K, Kalantarhormozi M, et al. Treatment of iron deficiency anemia in patients with subclinical hypothyroidism. Am J Med. 2013;126(5):420-4.
  9. Taymor, ML, Sturgis SH, Goodale WT, Ashbaugh D. Menorrhagia due to chronic iron deficiency. Obstet Gyneacol 1960; 16:571-576.
  10. Cinemre H, Bilir C, Gokosmanoglu F, Bahcebasi T. Hematologic effects of levothyroxine in iron-deficient subclinical hypothyroid patients: A randomized, double-blind, controlled study. J Clin Endocrinol Metab. 2009;94(1):151-156.
  11. Taymor ML, Sturgis SH, Yahia C. The etiological role of chronic iron deficiency in production of menorrhagia. JAMA 1964; 187:323-327.
  12. Beard J. Iron deficiency alters brain development and functioning. J Nutr. 2003; 133(5), 1468S-1472S.
  13. Walter T. Impact of iron deficiency on cognition in infancy and childhood. Eur J Clin Nutr 1993; 47:307-316.