In the last post I spoke about some of the main causes of insulin resistance.  In this post I am going to focus more on hypoglycemia.  I will then discuss seven factors which can help to balance blood sugar levels.  These will be important regardless of whether you have insulin resistance or hypoglycemia.

Hypoglycemia refers to low blood sugar levels, typically less than 70 mg/dL.  What happens is that either the body’s glucose is used up too quickly, is released into the bloodstream too slowly, or too much insulin is released into the bloodstream (1).  Some of the causes of hypoglycemia include alcohol consumption, an infection, hypothyroidism or hypoadrenalism, and severe heart, kidney, or liver failure (1).  I’ll talk more about these causes shortly.  Some of the common symptoms associated with low blood sugar levels include weakness, fatigue, sweating, disorientation, and shakiness (2).

Reactive hypoglycemia is an exaggerated fall in the blood glucose levels, and is due to excessive insulin secretion in response to a meal.  Dr. Alan Gaby has dedicated a chapter to reactive hypoglycemia in his excellent book “Nutritional Medicine”, and he discusses how if the blood glucose levels fall too rapidly then the body compensates by releasing adrenaline, as well as other compounds which raise the blood glucose levels.  This in turn results in “fight or flight” symptoms such as anxiety, panic attacks, hunger, palpitations, tachycardia, tremors, sweating, and even abdominal pain.  Dr. Gaby also talks about the symptoms presented when the blood glucose levels fall slowly over a period of hours, as this can lead to symptoms such as headaches, fatigue, blurred vision, mental confusion, impaired memory, and even seizures.  These symptoms usually are worse before meals, and frequently are relieved by eating.

Keep in mind that not everyone who has hypoglycemic symptoms will have low blood glucose levels or an abnormal glucose tolerance test.  And so this can be a challenging condition to diagnose.  I briefly mentioned some of the causes of hypoglycemia earlier, but there are other factors which might play a role in this condition, such as food allergies or sensitivities.

The following are some of the potential causes of hypoglycemia:

1) Eating refined foods and sugars.  Most people reading this know that eating a lot of refined foods and sugars will affect the blood sugar levels.  Eating a lot of refined sugars over a period of time will usually lead to hyperglycemia/insulin resistance, and eventually can set the stage for a condition such as type 2 diabetes.  However, in some people it can also lead to hypoglycemia.  Skipping meals frequently also can have a negative effect on the blood sugar levels and lead to hypoglycemic episodes.

2) Alcohol consumption.  Alcohol has a hypoglycemic effect, which is probably caused by the inhibition of gluconeogenesis in the liver (3) (4).  Gluconeogenesis involves the production of sugars (primarily glucose).  While having an occasional alcoholic beverage usually won’t lead to hypoglycemia, frequent consumption of alcoholic beverages can cause blood sugar imbalances.  And if anyone currently has blood sugar imbalances it probably would be a good idea to completely eliminate any alcohol consumption.

3) Thyroid hormone imbalance.  There is evidence that hypothyroidism can be a factor in hypoglycemia (5).  However, it is also possible that having hypoglycemia can inhibit the pituitary-thyroid axis (6).  And while hyperthyroidism isn’t usually associated with hypoglycemia, hyperthyroidism with congestive heart failure or liver dysfunction can induce hypoglycemia, although this is very rare (7).

4) Adrenal Insufficiency.  Hypoglycemia is one of the clinical manifestations of chronic primary adrenal insufficiency (8) (9).  Most cases of primary adrenal insufficiency are considered to be Addison’s disease, which is an autoimmune condition involving the adrenals.  However, secondary causes of adrenal insufficiency can also cause hypoglycemia (10) (11).  And so if someone has low cortisol levels, a low serum ACTH, and/or low DHEA levels, then this can be responsible for the hypoglycemic symptoms.

5) Acute infections.  Most cases of hypoglycemia aren’t caused by infections.  However, in some cases hypoglycemia can occur in bacterial sepsis (12) (13), or in bacteremic pneumococcal infections (14).

6) Food allergies or sensitivities.  Earlier I mentioned the book “Nutritional Medicine” by Dr. Alan Gaby.  In this book he mentions that “the ingestion of allergenic foods can trigger a hypoglycemic response in some people”.  Sometimes this can be challenging to determine, and in people with Hashimoto’s Thyroiditis and Graves’ Disease food sensitivities are common, although many times they are the result of a leaky gut, and don’t cause hypoglycemia.  However, if someone notices hypoglycemic symptoms upon eating a certain food, and if this pattern occurs every time after eating this food then one obviously should suspect that this food is responsible for the hypoglycemic effect.

How Can Blood Sugar Imbalances Be Corrected?

Diet.  Regardless of whether someone has hyperglycemia/insulin resistance, or hypoglycemia, eating well is very important.  Obviously you want to eat whole foods, and minimize the refined foods and sugars.  You also want to minimize your overall carbohydrate intake, and this is especially true if you’re suffering from insulin resistance, as when this is the case you will usually want to consume less than 150 grams of carbohydrates per day, and eating less than 100 grams of carbohydrates per day is sometimes necessary.  Keep in mind that I’m not suggesting that everyone should eat a low carbohydrate diet, but a big problem is that many people eat too many carbohydrates, which is one of the main reasons for the high incidence of insulin resistance and type 2 diabetes.

Although I love eating fruit, eating a lot of servings of fruit per day can cause problems in some people, and this is especially true in those with blood sugar issues.  If you are dealing with blood sugar imbalances it probably is a good idea to limit your consumption of fruit to one or two servings per day.  Even though fruit is high in phytonutrients and consists of natural sugars, you can still overdo it by eating too much fruit.

You also want to eat regularly throughout the day.  This is especially important for those who have hypoglycemia, although I think it’s important for most people to eat breakfast within one hour of waking up, and then every two to three hours after this.  Some people reading this might bring up the benefits of caloric restriction and intermittent fasting, which I wrote about in an article entitled “Intermittent Fasting and Thyroid Health“.  I agree that intermittent fasting can be beneficial, although it probably isn’t a good idea in someone who has hypoglycemia.

Address food sensitivities.  This seems to be more of a trigger with regards to hypoglycemic conditions, but of course even if someone doesn’t have any blood sugar imbalances they want to try to avoid any foods they are reacting to.  It can be very difficult to determine which foods you are sensitive to.  There is testing available such as IgE testing for food allergies, an IgG panel for delayed food sensitivities, and other types of testing such as the ALCAT.  These all can be valuable, but they also all have limitations.  And testing for food sensitivities can be very expensive, yet still provide false results.  I usually recommend an elimination diet for 3 to 4 weeks, followed by reintroducing the “suspicious” foods one at a time over a three day period.  This also has certain limitations, and of course takes more time than conducting a test for food sensitivities.

Improve insulin sensitivity.  It is also important to do things to improve insulin sensitivity.  This is especially important with insulin resistance, although it also can benefit those who have hypoglycemia as well.  Some of the best nutrients which can help to increase insulin sensitivity include chromium (15) (16) (17), magnesium (18) (19), and alpha lipoic acid (20) (21).  Vanadium (22) (23) and bitter melon (24) can also increase insulin sensitivity.  Berberine can benefit those with insulin resistance and type 2 diabetes by lowering blood glucose levels, and it might do this by modulating the microbiota (25).  The herb gymnema sylvestre can help to balance the blood sugar levels (26) (27).  You can also improve insulin sensitivity through exercise, which I’ll discuss next.

Exercise.  We all know that regular exercise is beneficial.  Although there are many nutrients which can increase insulin sensitivity, there is plenty of evidence which shows that exercise can also help to increase insulin sensitivity (28) (29) (30).  A big problem is that many people who exercise regularly also spend a good part of their day sitting.  So for example, someone might have a job that involves sitting behind a desk for most of the day, and then they expect three or four sessions of exercise each week to offset all of this inactivity.  Unfortunately this isn’t the way this works, as regular movement is very important.

Decrease inflammation.  Earlier I discussed how inflammation is a big factor in insulin resistance, and so one needs to do things to reduce the inflammatory process.  Obviously eating a healthy diet can help to reduce inflammation.  But it frequently is necessary to take nutrients to help break the inflammatory process.  I spoke about this in my blog post entitled “The Role of Cytokines In Autoimmune Thyroid Conditions“, as there is a transcription factor called Nuclear Factor Kappa B (NF-kB), and this needs to be downregulated.  Certain nutrients which can help with this include vitamin D, fish oils, turmeric, resveratrol, gamma-linolenic acid, ginger, and green tea.

Reduce oxidative stress. I also discussed how oxidative stress and mitochondrial dysfunction can play a role in insulin resistance.  And so doing things to reduce oxidative stress and improve the health of the mitochondria can be beneficial.  Some nutrients which can help with this include vitamin C, lipoic acid, acetyl-l-carnitine, CoQ10, resveratrol, and omega 3 fatty acids.

Correct dysbiosis.  Since intestinal dysbiosis can play a role in inflammation and insulin resistance, it is necessary to address this problem.  As I mentioned earlier, I have written a separate article on this topic, and so I would refer to this when you get the chance.

So hopefully you have a better understanding of the different factors which can cause insulin resistance and hypoglycemia, as well as some of the things you can do to address these health conditions.  Insulin resistance is when the body no longer is responsive to the effects of insulin, and some of the factors which play a role in the development of insulin resistance include inflammation, mitochondrial dysfunction, lipotoxicity, gut dysbiosis, circadian disruption, and genetics.  Hypoglycemia involves low blood sugar levels, and some of the potential causes of this condition include alcohol consumption, an infection, hypothyroidism, hypoadrenalism, as well as food allergies or intolerances.  Eating well and exercising regularly are both important factors when trying to regulate blood sugar imbalances, but some of these other factors I discussed in this post also need to be considered.

Many people with thyroid and autoimmune thyroid conditions have blood sugar imbalances.  However, there are different types of these imbalances.  Two of the most common health issues involving blood sugar imbalances are hypoglycemia and insulin resistance.  In the past I’ve spoken about these in separate articles, but since so many people suffer from blood sugar problems I figured it would be a good idea to talk about the similarities and differences between these two conditions.  In this post I will focus on insulin resistance, and then in the next post I will talk about hypoglycemia, and I will also discuss what you can do to correct blood sugar imbalances.

Glycemia refers to the presence of glucose in the blood.  As the name implies, hypoglycemia is a condition characterized by low blood sugar levels, whereas insulin resistance is more characteristic of hyperglycemia, which of course involves high blood sugar levels.  And the solution might seem simple, as if someone has high blood sugar levels  then they obviously want to reduce their sugar intake, and if someone has low blood sugar levels they will want to eat more regularly, right?  For the most part this is true, but while dietary factors are obviously important with both hypoglycemia and insulin resistance, these conditions are frequently complex and require more than simple dietary changes.

Before talking about insulin resistance I’d like to briefly talk about insulin.  Insulin is a hormone that is produced by the beta cells of the pancreas.  Insulin has numerous roles, but one of the primary roles is the regulation of blood glucose levels.  So when someone eats a meal, this will cause their blood sugar levels to rise, and the beta cells will secrete insulin to help the body utilize or store the glucose.

As for how insulin reduces blood glucose, it does so by inducing glucose uptake into insulin-sensitive tissues such as skeletal muscle, fat, and heart (1).  Insulin also inhibits glucose production in the liver, kidney, and small intestine in the control of blood glucose (1).  Insulin has other functions, as it stimulates the synthesis of fatty acids and glycogen (2), and it also plays a role in mitochondrial function.  What happens with insulin resistance is that the body is no longer responsive to the effects of insulin.  This in turn can lead to other conditions such as type 2 diabetes, accelerated atherosclerosis, hypertension or polycystic ovarian syndrome (3).

What Causes Insulin Resistance?                                                    

But in order to understand how to correct insulin resistance, it’s important to understand how insulin resistance develops.  Although eating a poor diet and a lack of exercise are definitely factors in many people, the development of insulin resistance is usually more complex.  Here are some of the factors which are thought to cause or contribute to insulin resistance:

1) Inflammation.  Inflammation is one of the biggest factors associated with insulin resistance, and this is one of the primary reasons why weight loss is so challenging in those with autoimmune thyroid conditions.  The following information is going to be somewhat advanced, but then I’m going to do my best to clarify it so that you better understand it.  Activation of immune cells is closely associated with insulin sensitivity, and research shows that classically activated (M1) macrophages sustain insulin sensitivity, whereas alternatively activated (M2) macrophages induce insulin resistance through the secretion of proinflammatory cytokines (4).  Apparently in a lean state Th2 cells, regulatory T cells, natural killer cells, or eosinophils contribute to the M2 activation of macrophages, whereas obesity causes alteration of the constituent immune cells, in which Th1 cells, B cells, neutrophils, or mast cells induce M1 activation of macrophages (4).

So what exactly does this mean?  Essentially the activation of certain immune system cells will cause insulin resistance, while the activation of others will decrease insulin resistance.  One of the main takeaways is that Th1 dominant conditions are more commonly associated with insulin resistance, whereas Th2 dominant conditions involve an increase in insulin sensitivity.  Since most people with Hashimoto’s Thyroiditis are Th1 dominant, this can be another mechanism which makes it difficult for people with this condition to lose weight.  If this is the case, the main factor which will help with losing weight is to suppress the autoimmune component and decrease the inflammation, which can be very challenging, and has been discussed in other blog posts and articles.  Graves’ Disease is in most cases a Th2 dominant condition, although this doesn’t mean that people with this condition can’t develop insulin resistance.

2) Mitochondrial dysfunction.  Mitochondria are located in the cytoplasm of our cells, and they are where cellular respiration occurs.  I’ve written a separate article on Mitochondria entitled “The Relationship Between Mitochondria and Thyroid Health“, and so if you’re not familiar with mitochondria I would read this article when you get the chance.  There is evidence that dysfunction of the mitochondria can play a role in insulin resistance (5) (6) (7).  But how can damage to the mitochondria cause insulin resistance?  Well, adipocytes (fat cells) play an important role in regulating energy metabolism and glucose homeostasis, and it appears that free radicals which are caused by mitochondrial dysfunction causes impairment of the function of adipocytes in maintaining glucose homeostasis (7).  So what this is essentially saying is that the mitochondria helps to regulate glucose homeostasis in fat cells, but when there is mitochondrial dysfunction, this causes free radicals, which in turn impairs the fat cells.

As a result, if someone has insulin resistance then it probably would be a good idea to do some things to help improve the health of the mitochondria.  But how can one tell if they have mitochondrial dysfunction?  Well, this can be challenging, and one of the methods of determining problems with the mitochondria is through an organic acids test, although other testing methods which can be useful include an amino acid analysis and a carnitine analysis (8).

3) Lipotoxicity.  Lipotoxicity refers to an excess of free fatty acids in certain tissues, which can include skeletal and cardiac muscle cells, hepatocytes (liver cells), and pancreatic beta cells (9) (10).  This can be a factor in insulin resistance and metabolic syndrome, and it will typically show up as elevated triglycerides on a lipid panel.  A good example of a condition associated with lipotoxicity is nonalcoholic fatty liver disease (NAFLD), which not surprisingly is usually associated with insulin resistance.  I’ve written a separate article on NAFLD entitled “Nonalcoholic Fatty Liver Disease and Thyroid Health“.  But just as a reminder, these fatty acids can accumulate in other cells as well, and not just the liver cells.

4) Gut dysbiosis.  Accumulating evidence indicates that the gut microbiota play a significant role in the development of obesity, obesity-associated inflammation, and insulin resistance (11).  Many people with thyroid and autoimmune thyroid conditions have gut dysbiosis, which I discussed in an article I wrote entitled “Intestinal Dysbiosis and Thyroid Health“.  I’ve also spoken about PCOS in the past, which is characterized by insulin resistance.  And there is evidence that gut dysbiosis can cause activation of the immune system, thus interfering with insulin receptor function, driving up serum insulin levels (12).

5) Circadian disruption.  I’ve spoken about the circadian rhythm in the past when discussing the adrenals and cortisol.  Circadian rhythms follow a 24-hour cycle.  So for example, cortisol is normally at the highest levels when a person first wakes up, and should be at the lowest levels right before going to bed.  The opposite is true with melatonin, as this hormone should be at the lowest levels upon waking up, and at the highest levels upon going to bed.  Many hormones that modulate insulin secretion and glucose homeostasis are regulated by the circadian system, and in addition to cortisol and melatonin, this includes hormones such as leptin, glucagon, growth hormone, and the catecholamines (13).  Disruptions in the circadian rhythm can lead to an increase in body weight, elevated leptin levels, and increased insulin secretion (14) (15).  As a result, if you are having problems with sleep, you most likely have problems with the circadian rhythm, which can be a cause of insulin resistance.

6) Genetics.  Yes, genetics is also a factor in insulin resistance.  However, just as is the case with most other chronic health conditions, lifestyle and environmental factors usually trigger the genetics.  Although some people are more susceptible to developing insulin resistance due to genetic factors, the good news is that it is possible to change the expression of our genes by modifying our lifestyle and environment.

So hopefully you have a better understanding with regards to the different factors that can cause insulin resistance.  In the next post I’m going to talk about hypoglycemia.  And then at the end of the post I will discuss seven factors which can help to balance the blood sugar levels.

For those people who have normal T4 levels, but low or depressed T3 levels, a thyroid hormone conversion problem needs to be suspected.  The thyroid gland mostly produces thyroxine, which is also known as T4.  The thyroid gland also produces a small amount of triiodothyronine, which is T3.  Most of the T3 is produced by the conversion of T4 to T3.  But there are numerous factors which can affect the conversion of T4 to T3, which I’ll be discussing in this post.

Before I discuss some of the factors which can affect the conversion of T4 to T3, I’d like to briefly talk about this process.  The enzyme 5′ -deiodinase is responsible for this conversion process.  There are three forms of this enzyme, which include deodinase type I, deodinase type II, and deodinase type III.  The type 1 and type II deiodinases are primarily responsible for the conversion of T4 to T3, whereas the type III deiodinase is mainly involved in the inactivation of T4 and T3 (1) (2).  Most of this conversion takes place in the liver, although some of the conversion also takes place in the gastrointestinal tract.  As a result, if someone has liver problems and/or gut dysbiosis then this can potentially affect the conversion of T4 to T3.  A certain percentage of T4 is also converted into reverse T3, which I have spoken about in a different post entitled “Reverse T3: What You Need To Know About It“.

So why is it a concern if someone has problems converting T4 into T3?  Well, T3 is the active form of thyroid hormone.  Unfortunately not all endocrinologists test for T3, but when they do they will either test for total T3, where most of T3 is bound to a protein, or free T3, which isn’t bound to a protein.  Free T3 is what actually binds to the thyroid receptor.  If someone has normal T4 levels but low T3 levels then this is considered to be a hypothyroid condition.  Many medical doctors will only test the TSH and T4 levels, and the reason for this is because if the T3 is low then the TSH will typically be elevated, although this isn’t always the case.  I always recommend testing both the free T3 and free T4, along with the TSH.  If doing an initial thyroid panel it’s also a good idea to test the reverse T3, along with the thyroid antibodies.

Why Do Most Medical Doctors Give Synthetic T4?

When someone presents with hypothyroidism, most medical doctors will recommend a form of levothyroxine, which is synthetic T4.  A common brand is Synthroid, although there are other forms as well.  But if T3 is what actually binds to the receptor, wouldn’t it make sense to give the person T3 instead?  Well, some medical doctors will recommend synthetic T3 in the form of Cytomel.  However, many doctors are understandably cautious about doing this, as too high of a dosage can put the person into a hyperthyroid state.  Synthetic T4 will convert into T3, but of course if someone has a conversion problem then this won’t be the case.  Plus, even if someone doesn’t have a conversion problem they might do better taking a natural form of thyroid hormone such as Armour or Nature-Throid, which consists of both T4 and T3, along with T1, T2, and calcitonin.

Now that you have a better understanding of the importance of T3, I’d like to discuss the five factors which can have a negative effect on the conversion of T4 to T3.

Factor #1: Problems with the liver.  Since most of the conversion of T4 to T3 takes place in the liver, it would make sense that some health conditions affecting the liver can decrease the conversion of T4 to T3.  However, this isn’t always the case, as one study which investigated the relationships between thyroid function in obese adolescents with non-alcoholic fatty liver showed that they had a  higher conversion of T4 to T3 due to increased deiodinase activity as a compensatory mechanism for fat accumulation (3).  With that being said, if someone has problems converting T4 to T3 it usually is a good idea to give some liver support, such as milk thistle and N-acetylcysteine.

Factor # 2: Gut dysbiosis. As I mentioned earlier, the good bacteria in the gut helps to convert T4 into T3 through the help of an enzyme called intestinal sulfatase.  There isn’t much evidence in the literature showing that gut dysbiosis negatively affects the conversion of T4 to T3, but obviously if someone has dysbiosis then this should be addressed even if they aren’t having a conversion issue.  I did come across one study which showed that Crohn’s disease can affect the conversion of T4 to T3 (4).

Factor # 3: Selenium deficiency.  The iodothyronine deiodinases all contain selenium in the form of selenocysteine, and they play crucial roles in determining the circulating and intracellular levels of T3 (5).  Numerous studies show that a selenium deficiency can affect the conversion of T4 to T3 (6) (7) (8).  However, this might only be the case with a severe selenium deficiency, as one study showed that only when selenium levels were decreased by more than 80% was deiodinase activity markedly decreased (5).

Factor # 4: Stress.  Elevated cortisol levels can affect the conversion of T4 to T3.  Studies show that stress can inhibit both type I iodothyronine 5′-deiodinase activity (9), as well as type II 5′-deiodinase activity (10) (11).  This is yet another reason why it’s important to improve your stress handling skills.

Factor # 5: Certain medications.  Amiodarone is an anti-arrhythmic compound, and due to the structural similarity between this and thyroid hormone it apparently inhibits the activity of 5′-deiodinase (12).  Beta blockers are commonly taken in hyperthyroid conditions, and certain ones such as propranolol, alprenolol, atenolol, and metroprolol can affect the conversion of T4 to T3 (13).

Factor # 6: Pro-inflammatory cytokines.  There is also evidence that certain pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) can inhibit type 2 5′-deiodinase (5’D-I) enzyme activity (14) (15) (16).  These cytokines are commonly present in autoimmune conditions, including Hashimoto’s Thyroiditis and Graves’ Disease.

In summary, normal T4 levels along with low T3 levels frequently indicate a conversion problem.  This involves the enzyme 5′-deiodinase, and is one reason why when obtaining a thyroid panel you want to not only look at the TSH and free T4 levels, but also the free T3.  And it usually is a good idea to look at the reverse T3 as well.  Six common factors which affect the conversion of T4 to T3 include problems with the liver, gut dysbiosis, a selenium deficiency, high cortisol levels, certain medications, and pro-inflammatory cytokines.

When someone with hyperthyroidism or Graves’ Disease is following a natural treatment protocol, the goal should be to address the underlying cause of the condition.  However, while this is being accomplished it is important to manage the hyperthyroid symptoms.  While many people choose to do this with antithyroid medication such as Methimazole or PTU, or beta blockers such as Propanolol, others choose to manage their symptoms naturally.  In this post I’ll discuss some of the most common herbs used to manage the hyperthyroid symptoms.

Bugleweed. This herb has antithyroid activity, as it reduces the thyroid hormone levels, which in turn causes a decrease in the cardiac symptoms associated with hyperthyroid conditions.  Lycopus virginicus and Lycopus europaeus are the two main species.  Most of the research studies involving bugleweed which I have come across have involved lycopus europaeus (1) (2) (3).  These studies show that bugleweed is effective in mild forms of hyperthyroidism, although in my clinical experience I’ve had patients with moderate to severe forms respond to a 1:2 extract ratio.  On the other hand, for some people this isn’t potent enough, and in these cases taking antithyroid medication may be necessary to lower the thyroid hormone levels while addressing the cause of the problem.

Dosage: According to master herbalist Kerry bone, 2 to 6 mL of a 1:2 liquid extract should be used, although I have used higher doses than this on some patients.  6 to 18 mL/day of a 1:5 tincture is recommended by Kerry Bone.

Pregnancy and Lactation: According to Kerry Bone, bugleweed is associated with a substantial risk of causing harmful effects on the fetus or neonate, and he suggests that it shouldn’t be taken during pregnancy.  He also says this herb is contraindicated during breastfeeding due to the possibility of both prolactin reduction in the mother and antithyroid constituents passing into the breast milk.

Motherwort. This herb can greatly help with the cardiac symptoms of hyperthyroid conditions.  It can help to reduce the heart palpitations, decrease the heart rate, and also has antiarrhythmic activity.  While bugleweed is specifically used for hyperthyroid conditions, motherwort can be beneficial for other conditions, such as digestive disorders, bronchial asthma, amenorrhea, and even externally in wounds and skin inflammation (4).  So in addition to its effects on the heart and circulatory system, pharmacological studies have confirmed its antibacterial, antioxidant, anti-inflammatory, and analgesic activity (4) (5).  The results of one study showed that motherwort can weaken the generation of free radicals in mitochondria (5), which is one of the ways that it offers cardioprotection.  Another small study looked at the effect of motherwort in patients with arterial hypertension accompanied by anxiety and sleep disorders, and concluded that this herb may help with arterial hypertension and concurrent psycho-neurological disorders, with minimal side effects (6).

Dosage: According to Kerry Bone, 2 to 4 mL of a 1:2 liquid extract should be used, although I have used higher doses of this in some patients.  If using a 1:5 tincture then 6 to 12 mL should be used by most people.

Pregnancy and Lactation. There has been no increase in frequency of malformation or other harmful effects on the fetus from limited use in women.  However according to Kerry Bone there is evidence of increased fetal damage in animal studies, and as a result I don’t recommend motherwort during pregnancy.  Kerry Bone does mention that it is compatible with breastfeeding, and I have had some breastfeeding women take motherwort.

Lemon Balm. In past articles and blog posts I have briefly mentioned the benefits of lemon balm for people with hyperthyroidism and Graves’ disease.  However, I’m admittedly biased towards bugleweed and motherwort since I took those two herbs when I was diagnosed with Graves’ Disease, although I didn’t take lemon balm.  However, lemon balm can benefit many people with hyperthyroid conditions.  It has antithyroid activity, as it may block the binding of TSH to its receptor by acting both on the hormone and receptor itself, and might also inhibit the TSH receptor antibodies binding to the TSH receptors (7).  Lemon balm also has been used as a mild sedative, spasmolytic, and antibacterial agent, and might even have antitumoral activities (8).  I also came across a few studies which showed that lemon balm has inhibitory activity on the herpes simplex virus (9) (10).  Another study showed that lemon balm can decrease elevated liver enzymes due to its strong antioxidant properties and phenolic compounds (11).  Another study conducted on mice showed that lemon balm has anti-diabetic effects, which is probably due to enhanced glucose uptake and metabolism in the liver and adipose tissue, and the inhibition of gluconeogenesis in the liver (12).

Dosage:  Kerry Bone hasn’t listed doses for lemon balm, and so if I recommend this herb I usually will start someone on the recommended dosage provided by the manufacturer.

Pregnancy and Lactation: Even though lemon balm has some antithyroid activity, some consider lemon balm to be safe during pregnancy, while others recommend to avoid it.  It does seem to be compatible with breastfeeding, although it might produce a mild sedative effect in the baby.

Hawthorn. Although I usually recommend motherwort to help manage the cardiac symptoms associated with hyperthyroidism (elevated pulse rate and palpitations), I also will recommend hawthorn at times.  This can also be helpful in those people with cardiac arrhythmias.  Hawthorn also has anti-inflammatory, gastroprotective, free radical-scavenging, and antimicrobial activity (13).  With regards to its antimicrobial activity, hawthorn seems to be most effective against gram-positive bacteria, with no effect on Candida albicans.

Dosage: According to Kerry Bone 3 to 7 mL of a 1:2 liquid extract should be used.  If someone is taking a 1:5 ratio then 9 to 20 mL should be used.

Pregnancy and Lactation: According to Kerry Bone, hawthorn has shown no increase in the frequency of malformation or other harmful effects on the fetus from limited use in women.  Just as is the case with motherwort, I typically don’t recommend hawthorn during pregnancy.  According to Kerry Bone, hawthorn is compatible with breastfeeding.

Reminder: The Quality Of The Herb Does Make A Difference

When someone is taking one or more of these herbs and they aren’t helping to manage the symptoms, one needs to consider a few factors.  First of all, the potency of the herb is important.  For example, some people will prepare herbal teas using one or more of these herbs, which can offer some benefit, but many times won’t be potent enough to manage the hyperthyroid symptoms.  If you purchase a liquid herb then the extract ratio is important.  For example, a 1:2 ratio is more potent than a 1:5 ratio.  There aren’t a lot of companies which sell bugleweed, but most that do offer it as a 1:5 ratio.  If you are taking bugleweed as a 1:5 ratio and it’s not helping then you might need to increase the dosage, or switch to a 1:2 extract.

Speaking of dosage, I always get emails from non patients asking what specific dosage of bugleweed or motherwort they should take.  Obviously this depends on the person, as if someone has thyroid hormone levels well outside of the reference range, along with a very high pulse rate, and they’re not taking antithyroid medication, then they most likely will require higher doses of these herbs.  On the other hand, if someone has slightly elevated thyroid hormone levels and a pulse rate which isn’t too high then they most likely will require a lower dosage.

Finally, the quality of the herb does make a difference.  So for example, if you go online and purchase some motherwort to help with the elevated heart rate and palpitations, and it doesn’t seem to be helping, while there’s a chance the dosage isn’t high enough, there’s also the chance that the quality of the herb is poor.  So before coming to the conclusion that motherwort isn’t effective you might want to try a different brand.  If you have been following me for awhile you know that I recommend working with a natural healthcare professional who has experience working with hyperthyroidism and Graves’ disease, as they will have experience dealing with the proper dosing, and they should be able to recommend some good quality brands.

Where Does L-Carnitine Fit In?

L-Carnitine isn’t an herb, but I figured I’d briefly mention it here since it can help to lower thyroid hormone levels when taken in higher doses.  This also isn’t something I personally took when I was diagnosed with Graves’ Disease, but over the years many of my patients have taken this.  For more information on L-carnitine I’d recommend reading my article entitled “How Does L-carnitine Help With Hyperthyroidism and Graves’ Disease?”

In summary, while the goal of a natural treatment protocol should be to restore the health of the person with hyperthyroidism and Graves’ Disease, managing the cardiac symptoms is important.  In many people this can be accomplished with herbs, and four herbs which can play a role in managing the hyperthyroid symptoms include bugleweed, motherwort, lemon balm, and hawthorn.  Both bugleweed and lemon balm have antithyroid activity, while motherwort and hawthorn help with the cardiac symptoms.  Motherwort, lemon balm, and hawthorn also have other benefits as well.  And L-carnitine taken in higher doses also can lower thyroid hormone levels.

In my articles and blog posts I frequently talk about detoxification. It’s quite common for my patients to have followed one or more liver detoxification programs prior to speaking with me for the first time. In fact, I’m sure many people reading this have gone through at least one liver detoxification program over the last few years. And some people have gone through multiple liver detoxifications over the last year alone. However, most people who follow a liver detoxification don’t have a good understanding of the detoxification pathways. As a result, in this post I would like to share some of the basics so that you better understand the different phases of detoxification.

There are two primary phases of detoxification. In the phase one detoxification system, which is known as “biotransformation”, certain toxins are converted into intermediate metabolites which can actually be more harmful than the original compound. In the phase two detoxification system, also known as the conjugation process, these intermediate metabolites are combined with certain molecules and become less toxic and water soluble. And then of course these metabolites are excreted, which is considered as being phase three detoxification. I mentioned how in phase one these toxins can be more harmful, as these intermediate metabolites can cause damage to the proteins, DNA, and RNA if they don’t go through phase two detoxification. As a result, this can be problematic if someone has compromised phase two activity.

What Role Do Cytochromes Play In Detoxification?

Cytochrome P450 enzymes are produced by the liver, and are also found in the kidney, small intestine, lung, adrenals, and most other tissues. They are utilized in phase one. There are 58 different cytochromes, and different cytochromes will play different roles in the metabolism of toxins, which include medications. The cytochrome P450 can be inhibited or induced by certain drugs, as well as by certain nutrients (1). An inducing agent can increase the rate of another drug’s metabolism, whereas an inhibiting agent can inhibit the drug’s metabolism.

These cytochrome P450 enzymes not only play a role in detoxification, as they are also essential in the metabolism of certain nutrients. For example, the cytochrome P450 enzymes are necessary for the metabolism of vitamin D (2), as well as vitamin E (3). These cytochromes are also necessary for the metabolism of hormones such as estrogen, as the first step in the metabolism of estrogens is the hydroxylation catalyzed by cytochrome P450 (4).

Genetic Polymorphisms Can Affect Detoxification

Polymorphisms are common genetic defects, and these can occur in the Cytochrome P450 (CYP) family, which in turn can affect the detoxification process. This is especially true with regards to the phase one metabolism of drugs, since almost 80% of drugs are metabolized by these enzymes (5). For example, if someone has a polymorphism of CYP2D6 then the individual would be considered to be a “poor metabolizer” (5). And polymorphisms of other CYP genes are also common, such as CYP1A1, 2A6, A13, 2C8, 3A4, and 3A5.

But what’s the significance of these genetic polymorphisms? Simply put, having certain polymorphisms of the CYP enzymes can reduce the person’s ability to detoxify. And some of these polymorphisms have been linked to chronic health conditions. For example, many people with hyperthyroidism and Graves’ Disease will commonly be advised by their endocrinologist to take Propranolol, which is a beta blocker. The cytochrome CYP2D6 is primarily responsible for the metabolism of Propranol (6), along with some other beta blockers, such as metoprolol (7). As a result, if someone were to have a genetic polymorphism of this cytochrome then this can affect the clearance of Propranol. Why is this important? Well, someone who has a polymorphism of CYP2D6 might require a different dosage of these beta blockers when compared to someone who doesn’t have such a polymorphism. Of course most people aren’t tested for these polymorphisms, and so the medical doctor will just recommend what he or she thinks is the appropriate dosage. In the future more and more people are going to be tested for these genetic polymorphisms, which in turn will impact the drug recommendations given by medical doctors.

But even though the focus of this post is on the detoxification pathways, these polymorphisms can cause other health issues. As I mentioned earlier, people who have a polymorphism of CYP2D6 are considered to be “poor metabolizers”. Well, a few studies have linked this polymorphism with Parkinson’s disease (8) (9). This doesn’t mean that everyone with this specific polymorphism will develop Parkinson’s, although it very well might make that person more susceptible to developing this condition. There is also evidence that some of these polymorphisms can increase one’s susceptibility to cancer (10).

Although I’ve been focusing on CYP2D6, there are many other types of polymorphisms of the cytochromes one can have, as I briefly listed some of them earlier. In addition to having polymorphisms of the cytochromes, there are other polymorphisms which can affect detoxification. For example, polymorphisms of glutathione S-transferase M1 (GSTM1) can have a negative effect on detoxification. N-Acetyltransferases (NAT) are key enzymes in the conjugation of certain drugs and other xenobiotics with an arylamine structure (11), and these polymorphisms can also affect detoxification.

How Can Nutrient Deficiencies Affect Detoxification?

Having certain nutrient deficiencies can have a negative effect on detoxification. And the reason for this is because nutrients are necessary for the proper functioning of the detoxification pathways. Some of the more important nutrients required for phase one detoxification include vitamins B2, B3, B6, B12, and folate. Many reading this are familiar with glutathione, which is an important antioxidant that also plays an important role in both phase one and phase two detoxification. The amino acids glycine, taurine, glutamine, cysteine, and methionine are all important for phase two detoxification.

However, when looking back at phase one detoxification, remember that intermediary metabolites are produced, and these can lead to the formation of free radicals. As a result, it is important to have sufficient antioxidants to help neutralize these free radical reactions. This not only includes glutathione, but others such as selenium and vitamin C.

The Complexity of The Phase Two Detoxification System

As I briefly mentioned earlier, phase two involves the conjugation of the intermediate metabolite with another molecule to make it less toxic and water soluble. While this might sound easy enough, it actually can be quite complex, as there are numerous pathways required in this phase. This includes acetylation, acylation, sulfur conjugation, methylation, and glucuronic acid conjugation. I’m not going to discuss these here, but just remember that having problems with any one of these pathways can affect phase two detoxification.

But what would cause these systems to malfunction? Well, there can be numerous factors which cause this. Having a genetic defect such as an MTHFR polymorphism can cause problems. Or having a certain nutrient deficiency can also lead to big issues. For example, if someone has a vitamin B5 (pantothenic acid) deficiency then this can affect acetylation. If they have a deficiency in glycine or taurine then this can affect acylation. If they have a deficiency of vitamin A or niacin then this can affect sulfation, etc. So for example, glutathione synthesis is magnesium-dependent. There are other important nutrients and amino acids required, but if someone has a severe magnesium deficiency, yet they take something such as N-acetyl cysteine to help increase glutathione levels, they won’t be able to accomplish this if the magnesium deficiency isn’t addressed.

Thyroid Health and Detoxification

Thyroid hormones play an important role in detoxification. Either a hypothyroid or hyperthyroid state can have a negative effect on the cytochrome P450 enzymes, which you now know play an important role in phase one detoxification. For example, one study in mice showed that hypothyroidism can affect the metabolism of xenobiotics by suppressing the CYP3A enzyme, while inducing the CYP2B enzyme (12). Numerous studies also show that a thyroid imbalance can affect the cytochrome enzymes (13) (14) (15).

So what does this mean? Well, it means that having hypothyroidism or hyperthyroidism can have a negative effect on detoxification. And so while it’s beneficial for people with these conditions to do things to detoxify their body, if they have a thyroid hormone imbalance then this can reduce the ability of body to metabolize toxins. And so it is important to correct any thyroid hormone imbalance in order to achieve optimal detoxification.

So hopefully you have a better understanding of the importance of the detoxification pathways. When someone undergoes a liver detoxification, the foods and supplements they are taking should support these pathways. If someone is deficient in one of these nutrients then this will have a negative effect on detoxification. However, having certain genetic polymorphisms can also have a negative effect on the detoxification pathways. In addition, having healthy thyroid hormone levels are also important for proper functioning of the detoxification pathways.