Micronutrients and Hypothalamic Amenorrhoea
It’s always best to get your vitamins, minerals and other micronutrients through whole foods, and only use supplements when absolutely necessary
Micronutrients and their role in HA recovery
Diet and nutrition can play a significant role in reversing functional hypothalamic amenorrhoea (FHA, here termed simply “HA”) and its effects. The last blog post discussed the macronutrients that may need to be considered when it comes to recovering your period and hormone health. If you haven’t read this yet, you can access it here.
What are micronutrients?
Unlike macronutrients which are needed in large amounts by the body, dietary micronutrients are needed in trace amounts. They include vitamins and minerals, which play vital roles in metabolism and the maintenance of tissue function. Although these nutrients are only needed in small amounts, deficiencies can have severe consequences for our health.
Below are the most well-researched micronutrients in relation to HA but as mentioned before, research is always developing and you may need different micronutrients to help with your recovery and hormone health.
Vitamin D
Vitamin D deficiency is common within the general population. Public Health England now recommends that everyone should take a daily supplement of 10mcg. Interestingly, low vitamin D status appears to be especially prominent among those with menstrual disturbances [1,2] and it’s certainly something I see a lot in clinic. Whilst the reasons for this trend are not fully understood, it is possible that low vitamin D status is secondary to reduced caloric intake and/or reduced dietary diversity, alongside other hormone-mediated changes in vitamin D metabolism. Research suggests that low oestrogen could exacerbate Vitamin D deficiency since oestrogen increases the activity of the enzyme responsible for activating vitamin D [3]. This could explain the increased prevalence of Vitamin D deficiency among those with HA.
What’s more, research indicates that vitamin D may play a regulatory role in ovulation with studies demonstrating clear associations between Vitamin D status and the menstrual cycle. In one study [4], low Vitamin D levels correlated with longer menstrual cycles, a longer follicular phase, and a shorter luteal phase. The mechanism for this is not yet known but may involve sub-optimal gonadotropin releasing hormone (GNRH), or defects in the ovarian response to gonadotropins, FSH and LH. A 2018 study concluded that women with low Vitamin D status (< 30ng/mL of 25-hydroxy vitamin D) were five times more likely to experience menstrual cycle disorders than those with adequate Vitamin D levels [5].
These findings suggest that the reproductive axis is sensitive to Vitamin D, making this vitamin an important consideration in HA and ovulatory health.
Vitamin D, alongside other key nutrients, also plays an important role in maintaining bone mineral density and the attainment of peak bone mass. Those with amenorrhoea (missing periods) are frequently found to have reduced bone density, which in turn increases the risk of osteoporosis and bone fractures. Oestrogen plays an important role in the growth and maturation of bone, as well as the regulation of bone turnover. Low oestrogen (a characteristic of HA) can negatively impact bone health, making it important to ensure that Vitamin D intake and production is as good as it can be in recovery.
Additionally, sub-optimal Vitamin D status has been observed in those with depression [6]. Although it is not yet known if low vitamin D is a causal factor in the development of depression or a result of associated behaviours (e.g., spending more time indoors away from the sun), it is an important consideration in those experiencing HA who may be more susceptible to mood disorders and mental health issues [7].
Calcium
Calcium works alongside Vitamin D and other nutrients to maintain bone health and achieve peak bone mass, providing a key structural element within bone tissues. Studies suggest that calcium status may be affected by stress, with significantly decreased plasma concentrations found in those experiencing emotional stress [8]. Other studies have suggested that mental illness may be associated with lower bone mineral density, especially in premenopausal women.
We know that stress is a common risk factor for HA and so it makes sense to ensure that those with missing periods and a diagnosis of functional hypothalamic amenorrhoea have adequate levels of calcium in their diet to avoid deficiency states and optimise bone health.
Where supplementation is medically required, it’s worth noting that supplemental calcium is best absorbed in small, more frequent doses and may interact with the absorption of other minerals when taken with foods. Certain forms of calcium are also better absorbed than others. Please speak to your doctor or registered nutrition provider if you have been prescribed calcium supplements as part of your treatment plan.
Magnesium
Evidence suggests that magnesium status may be depleted during periods of stress. A ‘vicious cycle’ is thought to exist whereby stress increases magnesium loss and thus risk of deficiency, whilst in turn, magnesium deficiency increases the body’s susceptibility to stress [9]. This is significant in the context of HA, which is largely a stress-mediated condition.
As well as stress, research has shown that strenuous exercise can deplete magnesium levels. Magnesium is involved in processes including oxygen uptake, energy production and electrolyte balance during muscle stimulation. Thus, exercise has been shown to increase urinary and sweat losses of magnesium and increase magnesium requirements by up to 10-20% [10]. This observation is of particular interest in those who exercise frequently and may provide a further contraindication for strenuous exercise during HA recovery.
Magnesium is also thought to play a role in the regulation of sleep. Although the mechanisms are not fully understood, magnesium is involved in the conductivity of ion channels and neural transmission at the cellular level [11]. This may be important in the context of HA, where a higher prevalence of sleep disorders exists [12].
What’s more, magnesium is a mineral involved in numerous enzymatic reactions in the body and studies have shown that magnesium is required to activate enzymes that metabolise Vitamin D.
It follows that magnesium deficiency could have an important knock-on effect on the status of other important nutrients required for HA recovery.
It's important to ensure that the individual risk for micronutrient deficiencies is assessed by a doctor or registered nutrition professional before any supplementation is considered. Certain forms of magnesium in supplement form are associated with unpleasant side effects, whilst dosages, timing of administration and interactions with medications and other supplements must be properly evaluated.
Iron
Although amenorrhoea means there is no menstrual loss of iron, low iron status may precede HA and could be secondary to restrictive diets or high intakes of anti-nutrients that prevent iron absorption, including fibre and phytates [13].
Like vitamin D, low iron status is something I see a lot in clinic, especially in those who are physically active, highly stressed or those with digestive issues.
Iron is a component of both haemoglobin and myoglobin, two oxygen-carrying proteins essential for physical performance. It is also a component of the enzymes and proteins involved in energy metabolism. In fact, research shows that iron deficiency may be more common in physically active females [14]. Loss of iron may occur via bleeding of the gastrointestinal tract following intense physical activity. Additionally, inflammation following physical activity may elevate levels of inflammatory cytokines, stimulating the expression of an iron-regulating hormone called hepcidin, which may contribute to reduced iron absorption in the small intestine. These factors combined may increase the risk of iron deficiency in those who exercise intensely.
Iron also plays an important role in both the synthesis and metabolism of thyroid hormones. It forms part of an enzyme called thyroid peroxidase, which is involved in the first steps of thyroid hormone production and thus low iron status may impair thyroid function [15]. This is potentially significant in the context of HA, which is often characterised by low energy availability which could theoretically be worsened by a state of reduced metabolism. Low levels of thyroid hormones in iron deficiency have also been associated with low body weight and decreased bone formation, both of which may be significant in patients with HA [16].
Finally, iron is also essential for the central nervous system. It is involved in various physiological processes including lipid metabolism, alongside myelin and neurotransmitter synthesis [17]. Numerous studies have investigated the association between iron status and mental health outcomes, with low iron cited as a risk factor for various psychiatric problems including stress, depression, anxiety, and bipolar disorder [18]. This makes iron an important micronutrient for those with functional hypothalamic amenorrhoea, which is commonly accompanied by stress and/or mental health challenges.
It’s important to note here that iron status must always be tested before supplementation. The body is unable to excrete excess iron and high iron levels can be toxic. Excess iron is also associated with lower concentrations of the hormone leptin [19], another factor identified in the development of HA. So, supplementation should only be considered under the supervision of a health professional.
Zinc
Zinc is a trace mineral involved in numerous enzymatic reactions in the body. Emerging evidence suggests that zinc may be involved in polycystic ovarian syndrome (PCOS), endometriosis and menstrual disturbances [20]. Although the mechanisms are not fully understood, zinc supplementation has been suggested to reduce insulin resistance, improve lipid balance, and reduce the severity of menstrual pain [20]. Although not directly related to HA, this is a developing area of research which points to the potential significance of zinc in reproductive function.
Additionally, a recent randomised control trial found that zinc supplementation reduced physical and psychological pre-menstrual symptoms including mood disturbances, breast tenderness, muscle pain, and bloating [21]. These findings could be relevant to those experiencing symptoms when recovering their periods.
What’s more, studies suggest that Zinc can be depleted during times of stress and physical endurance [22]. As chronic stress levels and physical activity are commonly associated with HA, this further highlights the importance of ensuring adequate zinc intake during recovery.
Folate
Studies suggest that folate may influence menstrual cycle regulation, ovulation, and fertility. Although mechanisms are not agreed upon, folate deficiency is thought to have deleterious effects on reproductive health, including DNA hypomethylation and oxidative stress [23].
Folate is a methyl donor and is involved in numerous, complicated metabolic pathways. Highly proliferating cells, such as developing ovarian follicles, may be particularly vulnerable to low folate levels, leading to a slowed ovarian response to gonadotropins, FSH and LH [24].
Folate deficiency also contributes to hypomethylation of DNA, resulting in ‘faulty’ DNA and can lead to an accumulation of the amino acid homocysteine as a by-product. Homocysteine is a reactive metabolite which can be mistakenly incorporated into proteins, jeopardising cellular function, and potentially generating reactive oxygen species, leading to oxidative stress. Oxidative stress itself has been linked with reduced reproductive function and menstrual disturbances [25].
Other research has shown that supplementation with folic acid could improve vascular function in HA. There is an observed relationship between oestrogen levels and brachial artery flow-mediated dilation (FMD). Coronary and peripheral vessels contain oestrogen receptors, allowing oestrogen to play a regulatory role in vascular function. As a result, amenorrhoeic athletes may have impaired vascular function due to reduced brachial artery FMD. In one study, folic acid supplementation (10 mg/day for 4 weeks) improved FMD in all subjects [26].
It is also worth mentioning that individuals with variations of the MTHFR gene are particularly vulnerable to folate deficiency [25]. This gene provides the instructions to make the MTHFR protein that is responsible for processing folate. Individuals with the MTHFR C677T polymorphism produce enzymes that are less efficient at processing folate, placing them at a higher risk of deficiency. Additionally, the MTHFR C677T polymorphism has been suggested to affect ovarian responsivity, with reduced oocyte (egg) sensitivity to FSH, reduced oocytes, and reduced oestradiol production by granular cells found amongst those with the mutation [27].
This mutation has implications for supplementation as the correct form of folate supplement is required. This highlights the benefit of seeking advice from a health professional who can provide relevant support if needed.
Micronutrients in functional foods
Functional foods are foods that have a potentially positive effect on health beyond basic nutrition. As well as vitamins and minerals, they contain other micronutrients like phytochemicals. Common phytochemicals include carotenoids, flavonoids, coumarins, indoles, isoflavones, lignans and plant sterols.
Flaxseed
Flaxseed is considered a functional food because it contains lignans, which are phytochemicals with weak oestrogenic and anti-oestrogenic properties. Consumption of flaxseed is thought to have several beneficial effects on menstruation. The observed effects include fewer anovulatory cycles, a longer luteal phase with a higher progesterone/ oestrogen ratio, reduced perception of stress and increased mid-follicular phase testosterone levels [28]. Flaxseed is also a good source of the omega-3 fatty acid, alpha-linolenic acid, the benefits of which were discussed in the last blog post.
In a 2003 study, phytoestrogens in flaxseed were shown to improve certain responses to stress, including a reduction in plasma cortisol during exposure to a stressor. This is a significant finding in the context of HA, where cortisol can play a role in suppressing the hypothalamus [29].
With the exception of flaxseed and potentially soy isoflavones, there is limited evidence for functional foods in the context of HA. A diverse and balanced diet that includes a range of macronutrients and micronutrients is encouraged. It is important to acknowledge that the benefits of specific foods and/or nutrients are likely to be highly individual, based on the nutritional profile and precise requirements of an individual on a case-by-case basis. It would be virtually impossible to recommend specific foods without an in-depth case history, food diary and clinical/laboratory testing.
Tips for increasing select micronutrient intake
Vitamin D
Recommended daily intake: 10µg
Note higher levels will be required under supervision to correct a deficiency
Food sources are limited but small amounts can be found in oily fish, red meat, liver, egg yolks + fortified foods.
The body can synthesise Vitamin D from sunlight during the summer months. Note, this is blocked by sunscreen + clothing.
In the UK, a daily supplement of 10 µg is recommended during the winter months.
Consider supplementing year-round if you have darker skin, if you always cover your skin when outdoors or spend a lot of time indoors.
Include fortified foods such as breakfast cereals and fortified yoghurts (check the label) to boost intake.
Calcium
Recommended daily intake: 700mg
Note, those with osteoporosis requiring treatment should have between 1000-1200mg per day
Food sources include cow, sheep and goat’s milk dairy, small-tinned fish with bones, tofu, sesame and poppy seeds, green leafy vegetables, fortified cereals, bread and dairy alternatives.
Use milk (or a calcium-fortified alternative) in hot drinks, porridge, and cooking.
Add grated cheese, ricotta, paneer or yoghurt to savoury dishes.
Try tinned sardines, pilchards or wild salmon (with bones) in a sandwich or on toast.
Look for calcium-fortified breakfast cereals.
Have a yoghurt with breakfast, or as a dessert/snack.
Have a glass of milk (or calcium-fortified alternative) to refuel after exercise.
Magnesium
Recommended daily intake 300mg
Food sources include green leafy vegetables like spinach and chard, wholegrains, nuts (especially cashews, almonds and Brazils), seeds (especially pumpkin, chia and flax), avocado, legumes, tofu, banana and dark chocolate.
Most people should consume enough magnesium from a healthy, balanced diet. However, if you are very active or under a lot of stress, consider increasing your overall intake of these foods.
Try to include some magnesium-rich foods following exercise (e.g., a banana and a handful of nuts).
Certain magnesium supplements can cause uncomfortable side effects. Always seek advice from a registered health provider.
Iron
Recommended daily intake: 14.8mg or 8.7mg post-menopause
Food sources include red meat and other animal proteins, shellfish, liver and other organ meats, beans and legumes, tofu, nuts, seeds, dried fruit, green leafy vegetables, dark chocolate and fortified products e.g. cereals.
Plant-based (non-haem) iron is generally not as well absorbed as animal-based (haem) iron.
Consuming plant-based iron with a source of Vitamin C (e.g., a glass of orange juice, lemon juice, fresh rocket, bell peppers or tomatoes) can help boost absorption.
Avoid consuming iron-rich foods alongside calcium-rich foods or caffeine as these can inhibit absorption.
Always test your iron levels before supplementing.
Zinc
Recommended daily intake: 7mg
Food sources include shellfish (especially oysters), meat, dairy, nuts (especially pine nuts, peanuts and cashews), legumes including peanuts, pumpkin and hemp seeds and wholegrains.
Sprinkle pine nuts onto pasta or salads or use a fresh pesto.
Add beans/legumes to meals such as chilli, casseroles, and stews.
Add pumpkins seeds or cashews to muesli, porridge or overnight oats
Try hummus with wholemeal pitta bread as a snack.
Shake things up with a seafood linguine, casserole or paella (great in the summer)
Folate
Recommended daily intake: 200µg or 400µg if trying to conceive
Food sources include green leafy vegetables like asparagus and Brussel sprouts, peas, chickpeas, lentils and other legumes, eggs, beetroot, citrus fruits, fortified cereals, beef liver and yeast or beef extract.
Folate is a water-soluble vitamin so it can be lost in cooking. To avoid this, try stir frying, lightly sautéing or steaming vegetables instead of boiling them.
Grate a little liver into Bolognese or chilli dishes.
Serve up a brunch with eggs, grilled asparagus and beets, with sautéed spinach and a squeeze of lemon
Folate in food is not always well absorbed [30], so including fortified products e.g., cereals may help meet requirements.
Take-home messages:
There are a variety of micronutrients that may be implicated in the development of HA. Sufficient energy intake, and dietary diversity, alongside nutritional assessment, are cornerstones of nutritional rehabilitation.
A balanced and varied diet containing enough calories should meet the requirements for most micronutrients (with the exception of Vitamin D). However, supplementation may be required to correct a deficiency.
A Vitamin D supplement of 10 µg/day is recommended for everyone in the UK.
Other micronutrients may need supplementing, particularly in HA recovery. This is largely individual and should only be determined under the advice and supervision of a fully qualified and registered nutrition or medical professional.
Stress, physical activity, and disrupted sleep can affect micronutrient status, so addressing these factors or any other underlying cause of low micronutrient levels is important.
The effect of exercise on micronutrient status may provide a further contraindication for strenuous exercise during HA recovery.
Important things to remember
Whilst it’s important to be aware of the important micronutrients needed for optimal health, some problems arise when assessing micronutrient status and the development of HA. The first of these is the potential issue of reverse causality (the chicken or the egg). Do low levels of vitamin D, for example, cause or contribute to HA, or does HA cause low vitamin D?
Secondly, laboratory findings (e.g., blood tests) may not always reflect the active forms of various nutrients. Careful clinical assessment combining laboratory tests, symptom history and dietary analysis is key. Unfortunately, a simple blood test from the doctor may not be enough to give the full picture and guide you.
Finally, it’s important to note that whilst this is an active and evolving area of research, clinical studies in HA remain limited. This article is an overview of some of the most well-researched micronutrients, although there may be other micronutrients not discussed here that may be of clinical importance to you, as an individual.
As always, it’s also important to remember that there is no one 'diet' that works for everyone. If you'd like to find out more about which foods and dietary modifications may help you, please book a free call so we can discuss your particular needs.
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This article was researched with the help of Emily Boorman (BSc Human Nutrition), a Band 4 Dietetic Assistant Practitioner and a wonderful intern at Holly Dunn Nutrition.
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